Factors related to first dose hypotensive effect of captopril: prediction and treatment.

The blood pressure response to the first dose of captopril (6.25 mg, 12.5 mg, or 25 mg) was measured in 65 treated, severely hypertensive patients. Mean supine blood pressure was 187/108 mm Hg immediately before captopril was given. Twenty one patients experienced a fall in supine systolic pressure greater than 50 mm Hg, including five whose pressure fell more than 100 mm Hg and two whose pressure fell more than 150 mm Hg. Six patients developed symptoms of acute hypotension, including dizziness, stupor, dysphasia, and hemiparesis. Percentage reductions in blood pressure were greatest in those with secondary hypertension (p less than 0.05), high pretreatment blood pressure (p less than 0.05), and high concentrations of plasma renin and angiotensin II (p less than 0.01). No significant correlation was found between fall in blood pressure and serum sodium concentration, age, renal function, and the dose of captopril given. A severe first dose effect cannot be consistently predicted in individual patients who have received other antihypertensive drugs for severe hypertension. Such patients should have close medical supervision for at least three hours after the first dose of captopril.     

Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy.

The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks'' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p less than 0.05) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) micrograms/min (p less than 0.05), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p less than 0.01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) micrograms/min (p less than 0.01), and glomerular filtration rate fell from 99 (SD19) to 93 (25) ml/min/1.73 m2 (p less than 0.01). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.     

Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation.

OBJECTIVE--To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes. DESIGN--Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction. SETTING--Patients attending diabetic outpatient clinic of city hospital. PATIENTS--Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy. INTERVENTIONS--After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month. END POINT--Reduction in blood pressure in type II diabetics with mild hypertension. MEASUREMENTS AND MAIN RESULTS--Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg). CONCLUSIONS--Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes.     

Randomised controlled trial of computer assisted management of hypertension in primary care.

The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested. Sixty family physicians were randomised to two treatment strategies. "Test" physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing. Computer feedback on management was mailed to the doctors. This encouraged doctors to apply the "stepped care" protocol, supplied charts of diastolic blood pressure v time, and ranked patients'' diastolic blood pressures by percentile. Letters were mailed to patients to remind them of appointments. "Control" doctors filled out the same data collection forms as test physicians, but neither doctors nor patients received computer feedback. Physicians who used the computer saw more patients per practice than control doctors (test 50 patients, control 40). For all patients the length of follow up was significantly longer in test practices (test 199 days, control 167), and a smaller percentage dropped out of active treatment in test practices (test 37.5%, control 42.1%). For patients with "moderate" hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practices (88.5 mm Hg), but it failed to reach this goal in control practices (93.3 mm Hg). A greater average reduction of diastolic pressure was achieved in test practices (test 21.7 mm Hg, control 16.7 mm Hg). Though patients with "moderate" hypertension were better controlled in test practices than in control practices, the patients in test practices visited their doctors less often (test 13.3 visits per patient-year, control 17.4 visits). Among patients with newly detected hypertension test practices achieved a greater reduction in diastolic pressure than control practices (test 15.1 mm Hg v control 11.3 mm Hg) and more sustained control of hypertension (test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days).     

The Angiotensin Infusion Test and Peripheral Venous Renin Activity

Forty hypertensive patients were studied to examine the assumption that the angiotensin pressor dose reflects endogenous renin activity. Peripheral renin activity was assayed by the method of Boucher et al.⁴ Sensitivity to the infusion of synthetic angiotensin II was determined as suggested by Kaplan and Silah.¹Sixteen patients with essential hypertension with normal renal angiography required 3.8 ng. angiotensin/kg./min. to raise the diastolic pressure 20 mm. Hg. All but one were sensitive to angiotensin infusion of less than 5 ng./kg./min. Renin activity was normal in all except in one sensitive subject. Angiotensin infusion response and mean renin activity in 13 patients with essential hypertension with abnormal renal angiography were similar to that of the first group. The pressor dose in 11 renovascular hypertensives was 9.8 ng./kg./min. All but three had elevated plasma renin activity.Our results suggest that: (1) the angiotensin infusion test is suitable for differentiating patients with true renovascular hypertension from those with essential hypertension with or without associated renal artery disease; (2) the angiotensin pressor dose correlates with the level of peripheral venous renin activity (p < 0.01).     

Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials

Objective To determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination.Design Meta-analysis of 354 randomised double blind placebo controlled trials of thiazides, β blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium channel blockers in fixed dose.Subjects 40 000 treated patients and 16 000 patients given placebo.Main outcome measures Placebo adjusted reductions in systolic and diastolic blood pressure and prevalence of adverse effects, according to dose expressed as a multiple of the standard (recommended) doses of the drugs.Results All five categories of drug produced similar reductions in blood pressure. The average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) at half standard dose. The drugs reduced blood pressure from all pretreatment levels, more so from higher levels; for a 10 mm Hg higher blood pressure the reduction was 1.0 mm Hg systolic and 1.1 mm Hg diastolic greater. The blood pressure lowering effects of different categories of drugs were additive. Symptoms attributable to thiazides, β blockers, and calcium channel blockers were strongly dose related; symptoms caused by ACE inhibitors (mainly cough) were not dose related. Angiotensin II receptor antagonists caused no excess of symptoms. The prevalence of symptoms with two drugs in combination was less than additive. Adverse metabolic effects (such as changes in cholesterol or potassium) were negligible at half standard dose.Conclusions Combination low dose drug treatment increases efficacy and reduces adverse effects. From the average blood pressure in people who have strokes (150/90 mm Hg) three drugs at half standard dose are estimated to lower blood pressure by 20 mm Hg systolic and 11 mm Hg diastolic and thereby reduce the risk of stroke by 63% and ischaemic heart disease events by 46% at age 60-69.     

Long-term follow-up of a hypertension screening program.

Of 185 people found to be hypertensive in a shopping centre screening program who went to their physician and had medication prescribed, then were contacted 18 months later, 33 had discontinued the medication at their physician''s request. But of 152 who were to continue taking medication 139 (91.4%) had complied. Blood pressure had decreased to less than 160 mm Hg systolic or less than 95 mm Hg diastolic, or both, in 65.1% of the 152; was 160 to 169 mm Hg systolic or 95 to 99 mm Hg diastolic, or both, in 13.8%; was mildly or moderately decreased but still above 169 mm Hg systolic or 99 mmHg diastolic, or both, in 8.6%; and was higher than before the onset of treatment in 3.9%. Adequacy of blood pressure control was not related to age, sex, initial blood pressure values, awareness before the screening of having hypertension, or treatment for hypertension before the screening. Diuretics had been prescribed for 93.5% of the 139 patients, most often as single-pill combinations with other antihypertensive agents.     

Telmisartan in the treatment of hypertension in patients with chronic renal insufficiency

The primary aim of this study was evaluation of the efficacy of telmisartan (angiotensin II receptor blocker- AT(1) blocker) on blood pressure in 10 patients with renal impairment in moderate or advanced stages of renal insufficiency and not dependent on haemodialysis. Its effect on proteinuria, renal function (represented by serum urea, creatinine, glomerular filtration), evaluation of overall therapy compliance in comparison with a previously prescribed angiotensin converting enzyme inhibitors (ACEI) were secondary aims. Considering the presence of left ventricle hypertrophy in all patients as a marker of hypertensive cardiopathy, the effect of telmisartan therapy on non-invasive cardiovascular parameters (ECG, echocardiography, and assessment of heart rate variability-HRV) was also evaluated. The study group involved 10 hypertensive patients (6 women, 4 men) with diabetic and non-diabetic renal impairment, proteinuria above 1 g/24 hours, hypertensive cardiopathy and intolerance of ACEI (cough). Telmisartan was added to their long-term antihypertensive combination therapy in a dose of 40 mg for the first 14 days, after which the dose increased to the maximal of 80 mg. The average initial daytime systolic blood pressure (SBP) was 149 +/- 19.7 mm Hg, average night-time SBP 145 +/- 23.0 mm Hg, average initial daytime diastolic BP (DBP) 90.6 +/- 2.5 mm Hg, night-time DBP 88.9 +/- 13.5 mm Hg. Average initial serum creatinine was 207.2 +/- 48.5 micromol/l, urea 15.1 +/- 4.4 mmol/l, GF 0.5 +/- 0.1 ml/s. Echocardiography revealed left ventricular (LV) hypertrophy with well preserved systolic and moderately impaired diastolic LV function. Also the HRV assessment revealed impaired neurovegetative (e.g. sympathovagal) balance. After 1 year of combination therapy with telmisartan, there was a clearly significant reduction in both SBP and DBP in both day and night-time (SBP daytime 149.6 vs.116.6 mm Hg, night-time 145.8 vs. 129.5 mm Hg; DBP daytime 90.6 vs. 83.5 mm Hg, night-time 88.9 vs. 79.3 mm Hg) and proteinuria (2.37 vs. 1.27 g/24 hour, p < 0.05). There were no significant changes in serum creatinine, urea values, and LV functions. On the other hand, further progression of the sympathovagal balance impairment was noted (continuing reduction of HRV in 9 from 10 patients), which can be described as the priority finding. The total compliance of telmisartan therapy was very good and without adverse clinical side effects. In conclusion - telmisartan reduces blood pressure and proteinuria safely and effectively in patients with various types of nephropathy in moderate or advanced stages of renal insufficiency.     

A new inorganic vasodilator, trans-[Ru(NO)(NH(3))(4)(POEt)(3)](PF(6))(3): hypotensive effect of endothelium-dependent and -independent vasodilators in different hypertensive animals models.

The hypotensive effect of RuNO was investigated in acute and chronic hypertensive rats, as well as in normotensive rats. Acute hypertension rats were used with 30% increase on basal BP (phenylephrine, angiotensin II (Ang II), N(G)-nitro-L-arginine methyl ester (L-NAME), and adult spontaneously hypertensive rats (SHR) (basal BP 168 +/- 3 mm Hg) were used as models for chronic hypertension. Rats were implanted with catheters (iv/ia) for BP measurements and for in bolus administration of RuNO, sodium nitroprusside (SNP), and acetylcholine (Ach) (10, 20, 40 nmol/kg, iv). The principal findings of this study were: (i) The hypotensive response to RuNO was 150% higher in acutely (phenylephrine and Ang II) and chronically (SHR) hypertensive rats than in normotensive rats, except in the case of L-NAME-induced hypertension (deltaMAP = 10 +/- 1.4 mm Hg). Chronic SHR showed 60% increase (deltaMAP = 19 +/- 0.8 mm Hg) in the effect compared to normotensive rats. (ii) The hypotensive response to SNP was lower (60%) in hypertensive rats than in normotensive rats, when compared to RuNO. However, the responses were similar in L-NAME-induced hypertension (deltaMAP = 30 +/- 2 mm Hg). (iii) The vasodilator response to Ach was increased in rats with Ang II-induced hypertension (deltaMAP = 53 +/- 1 mm Hg) and in SHR (deltaMAP = 67 +/- 3 mm Hg). RuNO response was more potent than SNP in hypertensive models and the increment in relation to normotensive was observed in the phenylephrine- and L-NAME-treated rats. This response could be correlated to the different endothelial dysfunction present in each model.     

Blood pressure control by home monitoring: meta-analysis of randomised trials

Objective To determine the effect of home blood pressure monitoring on blood pressure levels and proportion of people with essential hypertension achieving targets.Design Meta-analysis of 18 randomised controlled trials.Participants 1359 people with essential hypertension allocated to home blood pressure monitoring and 1355 allocated to the “control” group seen in the healthcare system for 2-36 months.Main outcome measures Differences in systolic (13 studies), diastolic (16 studies), or mean (3 studies) blood pressures, and proportion of patients achieving targets (6 studies), between intervention and control groups.Results Systolic blood pressure was lower in people with hypertension who had home blood pressure monitoring than in those who had standard blood pressure monitoring in the healthcare system (standardised mean difference 4.2 (95% confidence interval 1.5 to 6.9) mm Hg), diastolic blood pressure was lower by 2.4 (1.2 to 3.5) mm Hg, and mean blood pressure was lower by 4.4 (2.0 to 6.8) mm Hg. The relative risk of blood pressure above predetermined targets was lower in people with home blood pressure monitoring (risk ratio 0.90, 0.80 to 1.00). When publication bias was allowed for, the differences were attenuated: 2.2 (-0.9 to 5.3) mm Hg for systolic blood pressure and 1.9 (0.6 to 3.2) mm Hg for diastolic blood pressure.Conclusions Blood pressure control in people with hypertension (assessed in the clinic) and the proportion achieving targets are increased when home blood pressure monitoring is used rather than standard blood pressure monitoring in the healthcare system. The reasons for this are not clear. The difference in blood pressure control between the two methods is small but likely to contribute to an important reduction in vascular complications in the hypertensive population.     

Obesity as a determinant for response to antihypertensive treatment.

OBJECTIVE--To test the hypothesis that beta blockers lower blood pressure more effectively than calcium entry blockers in obese hypertensive patients and that calcium entry blockers are more effective in lean patients. DESIGN--Double blind, randomised controlled trial of treatment over six weeks. SETTING--Tertiary referral centre. SUBJECTS--42 white men with uncomplicated mild to moderate essential hypertension (World Health Organisation stage I or II); 36 completed the study. INTERVENTION--Patients were randomised to metoprolol 50-100 mg twice daily or isradipine 2.5-5.0 mg twice daily for six weeks after a two week run in phase. MAIN OUTCOME MEASURE--Blood pressure after six weeks of treatment. RESULTS--When stratified according to treatment and presence of obesity (body mass index < or = 27 kg/m2), the mean (SD) fall in blood pressure in the beta blocker group was 24 (13)/18 (10) mm Hg in obese patients and 18 (19)/12 (13) mm Hg in lean patients. In the calcium entry blocker group, the fall in blood pressure was 21 (15)/17 (6) mm Hg in lean patients and 18 (11)/8 (10) mm Hg in obese patients. After taking age and blood pressure before treatment into account there was a significant interaction between obesity and drug therapy (p = 0.019) with a better diastolic blood pressure response to calcium entry blockers in lean patients and to beta blockers in obese hypertensive patients. CONCLUSION--Obesity affects the efficacy of metoprolol and isradipine in reducing blood pressure.     

Hypertension after renal transplantation.

The incidence of hypertension (mean diastolic pressure above 90 mm Hg) was evaluated in 85 patients with renal transplants whose follow-up ranged from 3 to 84 months. Bilateral nephrectomy had been performed in 80 recipients. The proportion of hypertensive subjects rose during the first three months, subsequently stabilised around 50-60% for up to five years, and then decreased slightly during the next two years. Over the years hypertension fluctuated so that one-third of the initially hypertensive patients became normotensive, and over one-third of the initially normotensive patients became hypertensive. The main single aetiological factor was renal failure. A significant relation between steroid dosage and blood pressure was found in only a quarter of the hypertensive patients, and in another quarter no cause could be found.     

Community care compared with hospital outpatient care for hypertensive patients.

Three hundred and seventy-six patients with treated diastolic blood pressures of less than 105 mm Hg and no history of accelerated hypertension or renal failure were selected from among those attending the Hammersmith Hospital hypertension clinic. Their average lying treated blood pressure was 146 mm Hg systolic and 90 mm Hg diastolic and average age 56 years; 18% were black, 6% Asian, and 76% white. The patients were mostly having multiple treatment, 90% receiving a diuretic, 35% methyldopa, 33% propranolol, 18% atenolol, 9% hydrallazine, and 7% bethanidine. They were randomly allocated to either two years of further hospital outpatient care or referred back to their general practitioners. During the two years 19 (10%) of the 187 patients followed up in hospital defaulted and three had their treatment discontinued. Twelve (6%) of the 189 followed up by their general practitioners defaulted from follow-up and nine had their treatment discontinued. At the end of the trial the average lying blood pressure was 148 mm Hg systolic and 88 mm Hg diastolic in the hospital group and 149 mm Hg systolic and 90 mm Hg diastolic in the general practice group. The change in blood pressure was calculated for each individual and showed an average fall of 1.6 mm Hg in standing diastolic pressure in the hospital group and a rise of 1.4 mm Hg in the general practice group (p less than 0.05). The 90% confidence limits for a difference in standing diastolic pressure between the groups were 1 and 5 mm Hg with the pressure lower in the hospital group. General practice care was not quite as effective in controlling blood pressure as continued specialist supervision over two years in this selected group of treated outpatients with mild or moderate hypertension, but these results show that the discharge back to general practitioners of patients who are well controlled after hospital treatment is a sensible policy.     

Prolonged blood pressure reduction by orally active renin inhibitor RO 42-5892 in essential hypertension.

OBJECTIVE--To investigate the effects of a novel specific renin inhibitor, RO 42-5892, with high affinity for human renin (Ki = 0.5 x 10(-9) mol/l), on plasma renin activity and angiotensin II concentration and on 24 hour ambulatory blood pressure in essential hypertension. DESIGN--Exploratory study in which active treatment was preceded by placebo. SETTING--Inpatient unit of teaching hospital. PATIENTS--Nine men with uncomplicated essential hypertension who had a normal sodium intake. INTERVENTIONS--Two single intravenous doses of RO 42-5892 (100 and 1,000 micrograms/kg in 10 minutes) given to six patients and one single oral dose (600 mg) given to the three others as well as to three of the patients who also received the two intravenous doses. RESULTS--With both intravenous and oral doses renin activity fell in 10 minutes to undetectably low values, while angiotensin II concentration fell overall by 80-90% with intravenous dosing and by 30-40% after the oral dose. Angiotensin II concentration was back to baseline four hours after the low and six hours after the high intravenous dose and remained low for at least eight hours after the oral dose. Blood pressure fell rapidly both after low and high intravenous doses and after the oral dose and remained low for hours. With the high intravenous dose the daytime (0900-2230), night time (2300-0600), and next morning (0630-0830) systolic blood pressures were significantly (p less than 0.05) lowered by 12.5 (95% confidence interval 5.6 to 19.7), 12.2 (5.4 to 19.3), and 10.7 (3.2 to 18.5) mm Hg respectively, and daytime diastolic pressure was lowered by 9.3 (2.2 to 16.8) mmHg. With the oral dose daytime, night time, and next morning systolic blood pressures were lowered by 10.3 (5.5 to 15.4), 10.5 (4.2 to 17.2), and 9.7 (4.0 to 15.6) mm Hg, and daytime and night time diastolic pressures were lowered by 5.8 (0.9 to 11.0) and 6.0 (0.3-12) mm Hg respectively. CONCLUSIONS--The effect of the inhibitor on blood pressure was maintained over a longer period than its effect on angiotensin II. RO 42-5892 is orally active and has a prolonged antihypertensive effect in patients who did not have sodium depletion. This prolonged effect seems to be independent, at least in part, of the suppression of circulating angiotensin II.     

Lack of additional action of oxygen on pulmonary artery pressure at the peak of verapamil or captopril action in pulmonary hypertension secondary to mitral stenosis]

The aim of the study was to investigate whether oxygen causes a further decrease in pulmonary artery pressure after administration of calcium channel blocker-verapamil-or angiotensin converting enzyme inhibitor-captopril-in the secondary pulmonary hypertension. We studied 37 patients with the secondary pulmonary hypertension (mean pulmonary artery systolic pressure = 56.1 mm Hg) due to mitral stenosis. After having completed hemodynamic diagnostic procedures, basal oxygen test was performed and pulmonary artery pressure was recorded at 10 min of oxygen breathing. Then, 10 mg of verapamil was injected into the pulmonary artery of 16 patients and 21 patients received 75 mg of oral captopril. At the peak of vasodilation, 30 min after verapamil and 90 min after captopril administration, pulmonary artery pressure was recorded and oxygen test was repeated. Baseline oxygen test produced a statistically significant decrease in pulmonary artery pressure. Verapamil and captopril also lowered pulmonary artery systolic and diastolic pressures. The second oxygen test did not cause a further decrease in the pulmonary artery pressure; mean pulmonary artery systolic pressure was 52.3 +/- 23.7 mm Hg, pulmonary artery diastolic pressure 22.7 +/- 10.6 mm Hg before and 49.1 +/- 23.8 mm Hg and 23.0 +/- 13.5 mm Hg, respectively after the test in verapamil group, and 47.0 +/- 15.5 mm Hg and 21.7 +/- 8.4 mm Hg before and 46.6 +/- 15.4 mm Hg, respectively in captopril subset. The results may support the thesis that vasodilating effect depends rather on the degree of pulmonary vascular changes than on the vasodilatory mechanism of particular drugs.     

Individual variation between general practitioners in labelling of hypertension.

Variation in labelling of hypertension by individual general practitioners was studied during a continuous opportunistic screening programme for hypertension in a single general practice with 12 principals. All the general practitioners agreed to label as hypertensive patients with systolic pressures of greater than or equal to 200 mm Hg or diastolic pressures of greater than or equal to 110 mm Hg on three consecutive readings. The overall number of patients labelled hypertensive at the beginning of the screening programme was 505 and this rose to 801 after five years. There was a large variation in the numbers of patients recorded as hypertensive at the start of the screening period, with numbers ranging from eight to 112 for individual practitioners. The variation persisted during the screening period, with the numbers of patients detected by individual general practitioners ranging from four to 46. The average systolic and diastolic pressures recorded among these patients also varied between doctors, and only 24 out of 187 patients had their high pressures recorded on three occasions and so fully met the criteria for diagnosing hypertension. Clearly, general practitioners are following their own individual criteria in defining hypertension and taking into account factors other than just the measured blood pressure.     

Toward gene therapy of hypertension: Experimental study on hypertensive ISIAH rats

TiO₂-based nanocomposites were prepared to deliver oligonucleotides into cells. The nanocomposites were designed by the immobilization of polylysine-containing oligonucleotides on TiO₂-nanoparticles (TiO₂·PL-DNA). We showed for the first time the possibility of using the proposed nanocomposites for treatment of hypertensive disease by introducing them into hypertensive ISIAH rats developed as a model of stress-sensitive arterial hypertension. The mRNA of the gene encoding angiotensin I-converting enzyme (ACE1) involved in the synthesis of angiotensin II was chosen as a target. Administration (intraperitoneal injection and inhalation) of the nanocomposite showed a significant (by 20-30 mm Hg) decrease in systolic blood pressure when the nanocomposite contained the ACE1 gene-targeted oligonucleotide. When using the oligonucleotide with a random sequence, no effect was observed. Further development and improvement of the inhalation nanocomposite drug delivery to systemic hypertensive disease treatment promises new possibilities for clinical practice.     

Role of angiotensin II in oral contraceptive hypertension in anesthetized rats

Rats fed a diet containing an oral contraceptive estrogen-progestogen mixture (Enovid) for 26 weeks developed a significant (P<0.01) elevation in mean arterial pressure (145 ± 6 mm Hg) when compared to a control group of rats fed the same diet without oral contraceptive steroids (mean arterial pressure averaged 117 ± 6 mm Hg). Infusion of [Sar¹, Ala⁸] angiotensin II, a competitive antagonist of angiotensin II, reduced the mean arterial pressure (P<0.01) in the oral contraceptive-treated rats to 117 ± 9 mm Hg, while infusion of this angiotensin II analogue into the control rats did not lower the arterial pressure. These studies provided evidence that angiotensin II may be involved in the hypertension produced by Enovid treatment in rats.     

Screening for hypertension in a high school population.

Of 15 594 high school students (ages, 15 to 20) whose blood pressure was measured in a screening program, 350 (2.2%) has hypertensive readings (150 mm Hg or more systolic, or 95 mm Hg or more diastolic, or both). The mean blood pressure for the boys was 125.0 plus or minus 12.1/71.8 plus or minus 10.9 mm Hg, and for the girls, 119.8 plus or minus 10.2/72.3 plus or minus 9.2 mm Hg. The parents of the students with hypertensive readings were advised to send their children to a physician. By 6 months, of the 232 who were followed up, 156 (67.2%) has visited a physician and in 19 cases (12.2%) the physician had confirmed the hypertensive readings. Only one student, an asymptomatic 17-year-old boy whose hypertension had not previously been detected, was found to have secondary hypertension, which was relieved surgically. Of the 18 hypertensive students 4 are currently receiving antihypertensive medication and 8 continue to have their blood pressure monitored. The mean blood pressures recorded in the physicians'' offices averaged 23.7/11.1 mm Hg less than those recorded in the schools. One reason for this was that none of the physicians used pediatric cuffs, but these were required by 62.4% of the students at the screening. Hence, the intravascular blood pressure was probably underestimated in a number of cases in the physicians'' offices.     

Hypothalamic angiotensinergic-noradrenergic systems interaction in fructose induced hypertension

OBJECTIVE: Several studies suggest the importance of the interaction between the renin angiotensin and sympathetic nervous systems in blood pressure control, especially in clinical situations such as the metabolic syndrome. Previously, we have demonstrated changes in noradrenergic hypothalamic control of blood pressure in an animal model of insulin resistance and hypertension. The aim of the present study was to evaluate the effects of the interaction between the noradrenergic and angiotensinergic systems on hypothalamic blood pressure regulation in fructose hypertensive rats. METHODS: In control (C) and fructose-fed hypertensive (F) rats, we studied: 1) the effects of hypothalamic perfusion of irbesartan (AT(1) angiotensin receptor antagonist, 50 and 500 microg ml(-1)) and metoprolol (beta(1) adrenergic receptor antagonist, 10 and 100 microg ml(-1)) on blood pressure, heart rate and noradrenaline intrahypothalamic levels, by means of the microdialysis technique; and 2) the effects of intrahypothalamic microinjection of angiotensin II alone or after metoprolol pre-administration, on blood pressure and heart rate. RESULTS: Meanwhile irbesartan perfusion did not modify neither mean arterial pressure (MAP) nor heart rate or noradrenaline hypothalamic levels in the C group, its highest dose diminished MAP (DeltaMAP: F: - 16.3+/-1 mm Hg, p<0.05) and noradrenaline levels (% of basal levels: 58+/-7%, p<0.05) in the F group, without affecting heart rate. Intrahypothalamic perfusion of metoprolol diminished MAP only in the F group (DeltaMAP: F: -12.1+/-1.1 mm Hg, p<0.05), but did not modify heart rate in both groups. On the other hand, it diminished noradrenaline hypothalamic levels in C (% of basal levels: 53+/-6%, p<0.05) but not in the F group. The pressor response to angiotensin II microinjection was increased in F rats (DeltaMAP: F: 13.3+/-1.5 mm Hg vs. C: 6.9+/-1.8 mm Hg; p<0.05). Previous administration of metoprolol markedly abolished this increment. CONCLUSIONS: Our results suggest the existence of an increase in AT(1) and beta(1) adrenergic receptors tone in the hypothalamus of F rats, which could be related to the increase in blood pressure present in this experimental model. On the other hand, considering that the enhanced pressor response to angiotensin II intrahypothalamic injection in F rats was abolished by previous administration of a beta(1) adrenergic receptor antagonist, these results would indicate that beta(1) adrenergic receptors activation participates in the pressor response to angiotensin II in this experimental model of insulin resistance and hypertension.