Hemodynamic Response to Exercise After Beta-Adrenergic Blockade with Propranolol in Patients with Mitral Valve Obstruction

Propranolol (P) .13 mg./kg. was given to seven patients with mitral valve obstruction the changes in resting and exercise hemodynamics were followed by means of combined right and left heart catheterization. Changes were variable. At rest there was a decrease in heart rate of 10 beats/min. with no consistent change in stroke volume, cardiac output, left ventricular systolic (LVS) or left atrial (LA) pressure after P. Mean left ventricular end-diastolic (LVED) pressure was increased 3 mm., mean pulmonary artery (PA) pressure was increased 4 mm., and mean mitral valve gradient was reduced 3 mm. Hg by P. During exercise, mean LVS pressure was decreased 31 mm., mean LVED pressure increased 3 mm., mean LA pressure decreased 3 mm., and mean mitral valve gradient was reduced 5 mm. Hg after P. Mean exercise PA pressure was unchanged, cardiac output was reduced 0.9 1./min., and mean heart rate was reduced 37 beats/min., while stroke volume increased 3 ml./beat after P. Exercise pulmonary vascular resistance was increased from 6.1 to 8.2 units by P. Despite a slower heart rate, the diastolic filling period was not increased. P has no place in the treatment of the majority of patients with mitral stenosis because it further reduces cardiac performance below normal.     

Separate hemodynamic roles for chloride and sodium in deoxycorticosterone acetate-salt hypertension

It has been reported that both sodium and chloride ions must be ingested to induce the elevated blood pressure of deoxycorticosterone acetate (DOCA)-salt-sensitive hypertension. This study was designed to determine the separate roles of the sodium and chloride ions in the altered hemodynamics underlying the high blood pressure. DOCA pellets (75 mg) were implanted in uninephrectomized rats and the animals were then fed one of four diets: (i) high sodium chloride, (ii) high sodium-low chloride, (iii) high chloride-low sodium, or (iv) low sodium chloride. Blood pressures were measured weekly by tail-cuff plethysmography for 5 weeks and the animals were then subjected to a terminal experiment to measure cardiac output by thermodilution technique, renal blood flow by electromagnetic flow probe, and direct arterial pressure. Blood pressure in the DOCA-high NaCl group was significantly greater (P less than 0.05) compared with that of the DOCA-low NaCl group (160 +/- 3 mm Hg vs 124 +/- 2 mm Hg, respectively) at 5 weeks after treatment; all other groups were not significantly different from the DOCA-low NaCl group. Cardiac output was significantly greater in DOCA-treated rats consuming diets high in sodium (44 +/- 2 ml/min/100 g) or sodium chloride (40 +/- 2 ml/min/100 g) compared with animals consuming low sodium chloride (31 +/- 2 ml/min/100 g; P less than 0.01 for each comparison). Direct intraarterial blood pressure and renal blood flow were used to calculate renal vascular resistance. Renal vascular resistance was increased in those DOCA-treated rats consuming diets high in chloride (42 +/- 3 mm Hg/ml/min/100 g) and high sodium chloride (54 +/- 3 mm Hg/ml/min/100 g) compared with rats consuming low sodium chloride (30 +/- 3 mm Hg/ml/min/100 g; P less than 0.01 for each). It appears that elevations in cardiac output are associated with increased dietary sodium and act in synergy with the elevations in renal vascular resistance associated with increased dietary chloride. Increases in both cardiac output and renal vascular resistance are involved in the maintenance of elevated blood pressure in the DOCA-salt-sensitive model of hypertension.     

Lifestyle modifications to prevent and control hypertension. 5. Recommendations on dietary salt. Canadian Hypertension Society,Canadian Coalition for High Blood Pressure Prevention and Control,Laboratory Centre for Disease Control at Health Canada,Heart and Stroke Foundation of Canada

OBJECTIVE: To provide updated, evidence-based recommendations concerning the effects of dietary salt intake on the prevention and control of hypertension in adults (except pregnant women). The guidelines are intended for use in clinical practice and public education campaigns. OPTIONS: Restriction of dietary salt intake may be an alternative to antihypertensive medications or may supplement such medications. Other options include other nonpharmacologic treatments for hypertension and no treatment. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A MEDLINE search was conducted for the period 1966-1996 using the terms hypertension, blood pressure, vascular resistance, sodium chloride, sodium, diet, sodium or sodium chloride dietary, sodium restricted/reducing diet, clinical trials, controlled clinical trial, randomized controlled trial and random allocation. Both trials and review articles were obtained, and other relevant evidence was obtained from the reference lists of the articles identified, from the personal files of the authors and through contacts with experts. The articles were reviewed, classified according to study design and graded according to level of evidence. In addition, a systematic review of all published randomized controlled trials relating to dietary salt intake and hypertension was conducted. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: For normotensive people, a marked change in sodium intake is required to achieve a modest reduction in blood pressure (there is a decrease of 1 mm Hg in systolic blood pressure for every 100 mmol decrease in daily sodium intake). For hypertensive patients, the effects of dietary salt restriction are most pronounced if age is greater than 44 years. A decrease of 6.3 mm Hg in systolic blood pressure and 2.2 mm Hg in diastolic blood pressure per 100 mmol decrease in daily sodium intake was observed in people of this age group. For hypertensive patients 44 years of age and younger, the decreases were 2.4 mm Hg for systolic blood pressure and negligible for diastolic blood pressure. A diet in which salt is moderately restricted appears not to be associated with health risks. RECOMMENDATIONS: (1) Restriction of salt intake for the normotensive population is not recommended at present, because of insufficient evidence demonstrating that this would lead to a reduced incidence of hypertension. (2) To avoid excessive intake of salt, people should be counselled to choose foods low in salt (e.g., fresh fruits and vegetables), to avoid foods high in salt (e.g., pre-prepared foods), to refrain from adding salt at the table and minimize the amount of salt used in cooking, and to increase awareness of the salt content of food choices in restaurants. (3) For hypertensive patients, particularly those over the age of 44 years, it is recommended that the intake of dietary sodium be moderately restricted, to a target range of 90-130 mmol per day (which corresponds to 3-7 g of salt per day). (4) The salt consumption of hypertensive patients should be determined by interview. VALIDATION: These recommendations were reviewed by all of the sponsoring organizations and by participants in a satellite symposium of the fourth International Conference on Preventive Cardiology. They have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at Health Canada, and the Heart and Stroke Foundation of Canada.     

Intravenous diazoxide in treatment of hypertension associated with recent myocardial infarction

Twenty patients with blood pressure over 180/110 mm Hg one hour after admission to a coronary care unit with recent acute myocardial infarction were given intravenous diazoxide in a bolus of 300 mg. The average blood pressure before diazoxide was 194/122 mm Hg. Blood pressure fell considerably in all patients, though six patients required two injections. The average fall was 58 mm Hg systolic and 40 mm Hg diastolic. No patient became severely hypotensive. The heart rate increased by an average of 10 beats/min. In nine patients the electrocardiographic changes immediately after the administration of diazoxide suggested an increase in myocardial injury. Though none of the patients seemed to deteriorate clinically from the diazoxide the electrocardiographic changes suggested that the use of intravenous diazoxide to lower blood pressure in patients with acute myocardial infarction might possibly be deleterious.     

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.     

Intravenous urocortin II decreases blood pressure through CRF(2) receptor in rats

Urocortin II (Ucn II) is a new member of the corticotropin-releasing factor (CRF) family that binds selectively to the CRF subtype 2 receptor (CRF(2)). CRF or urocortin injected intravenously (i.v.) induced hypotension. We investigated the influence of iv human Ucn II (hUcn II) on basal mean blood pressure (MAP) and on the sympathetic mediated hypertensive response to TRH analog, RX-77368 injected intracisternally (i.c.) 20 min after hUcn II in urethane-anesthetized rats. Ucn II (3, 10, and 30 microg/kg, i.v.) significantly decreased basal MAP from baseline by -20.9+/-6.5, -21.3+/-5.4 and -46.8+/-6.5 mm Hg, respectively, after 10 min. RX-77368 (30 ng, i.c.) elevated MAP for over 90 min with a maximal hypertensive response at 20 min. Ucn II (3, 10, and 30 microg/kg, i.v.) did not alter the 20 min net rise in MAP induced by RX-77368 (35.7+/-7.1, 32.6+/-3.3 and 24.6+/-6.9 mm Hg, respectively) compared with vehicle (33.6+/-4.3 mm Hg). The selective CRF(2) antagonist, astressin(2)-B (60 microg/kg, i.v.) abolished hUcn II hypotensive action while having no effect on basal MAP. These data show that iv hUcn II induces hypotension through peripheral CRF(2) receptor while not altering the responsiveness to sympathetic nervous system-mediated rise in MAP.     

Effect of phosphatidylinositol 3-kinase-γ inhibitor CAY10505 in hypertension, and its associated vascular endothelium dysfunction in rats

This study has been designed to investigate the role of phosphatidyl-inositol 3-kinase-γ (PI3Kγ) in deoxycorticosterone acetate salt (DOCA) hypertension induced vascular endothelium dysfunction. Wistar rats were uninephrectomised and DOCA (40 mg·(kg body mass)(-1), subcutaneous injection) was administered twice weekly for 6 weeks to produce hypertension. Rats with mean arterial blood pressure ≥ 140 mm Hg (1 mm Hg = 133.322 Pa) were selected as hypertensive. Vascular endothelium dysfunction was assessed in terms of attenuation of acetylcholine-induced endothelium-dependent relaxation (isolated aortic ring preparation), decrease in serum nitrate and (or) nitrite level, as well as reduced level of glutathione and disruption of integrity of vascular endothelium (histopathology). Five weeks of DOCA administration were followed by 7 days of daily administration of PI3Kγ inhibitor (5-[[5-(4-fluorophenyl)-2-furanyl]methylene]-2,4-thiazolidinedione (CAY10505), 0.6 mg·kg(-1), per os (p.o.)), atorvastatin (30 mg·kg(-1), p.o.), and losartan (25 mg·kg(-1), p.o.) (positive control of hypertension), which significantly improved acetylcholine-induced endothelium dependent relaxation, serum nitrate and (or) nitrite level, glutathione level, and the vascular endothelial lining in hypertensive rats.Therefore, it may be concluded that CAY10505, a specific inhibitor of PI3Kγ, improves hypertension-associated vascular endothelial dysfunction. Thus, inhibition of PI3Kγ might be a useful approach in the therapeutics of vascular endothelium dysfunction.     

Initial blood pressure fall on stand up and exercise explained by changes in total peripheral resistance

To elucidate the underlying mechanisms of the initial fall in blood pressure on standing upright from the supine position, we measured the beat-to-beat changes in intra-arterial pressure in eight healthy male subjects in response to standing. Changes in stroke volume, cardiac output, and total peripheral resistance were computed from the pressure waveform using a pulse contour method. To determine possible mechanisms for the changes observed on standing, similar measures were made on passive tilting and a brief (3-s) bout of cycle exercise. Standing elicited a transient 25% (23-mmHg) fall in mean blood pressure as a result of a 36% fall in total peripheral resistance. Head-up tilt elicited a gradual change in haemodynamic parameters, which reached plateau levels in 20-30 s. Cycling elicited a transient 17% (18-mmHg) fall in blood pressure and a 41% fall in total peripheral resistance. In addition, we measured right atrial and esophageal pressures in two subjects on standing and cycling and found a 10- to 15-mmHg rise in right atrial pressure without a corresponding change in esophageal pressure. This points to the cardiopulmonary reflex as the primary effector of peripheral vasodilation, but we cannot exclude the possibility that 1) local metabolic vasodilation and 2) central command-mediated cholinergic vasodilation contributed to the fall in vascular resistance.     

Noninvasive determination of small vessel distensibility in man

The present study describes and illustrates a noninvasive method for computing extensibility of the 'resistance vessels', from an experimentally obtained resistance vs transmural pressure plot, in a maximally dilated vascular bed of man. Limb blood flow was measured plethysmographically following 10 min of arterial occlusion, and blood pressure was measured by the arm cuff method. A ratio of two resistance values taken 30 mm Hg apart was used to compute percent change in radius and the extensibility, E. The computed values of E were 0.71 mm Hg-1 for normal hand and 0.13, 0.22 and 0.69 for the hypertensive forearm, hand and finger respectively. These results indicate that the method may prove useful in the understanding and management of diseases such as hypertension or other small vessel diseases.     

Augmented chemoreceptor reflex tonic drive in early human hypertension and in normotensive subjects with family background of hypertension

The study was carried out in 30 subjects with mild primary hypertension and in 82 normotensive age-matched volunteers, 18-20 years of age. Hyperoxia test was used to withdraw the tonic chemoreceptor reflex drive. The following circulatory and respiratory effects of short lasting hyperoxia were observed in the hypertensive group and in most of the normotensive subjects yet with a family background of hypertension: a decrease in the mean arterial pressure, in total peripheral vascular resistance, and in forearm vascular resistance, and a significantly greater reduction of the resting ventilation as compared to the normotensive group. Our results suggest that the augmented arterial chemoreceptor drive is one of the mechanisms responsible for the elevated arterial blood pressure and total peripheral resistance in early human hypertension. The positive response to hyperoxia test in healthy subjects with a family background of hypertension suggests a familial occurrence of the hyperactivity of the arterial chemoreceptors.     

Kinetics of serotonin in platelets in essential hypertension.

In a study of the kinetics of 5-hydroxytryptamine (5-HT) in platelets in 26 hypertensive subjects with a mean systolic and diastolic blood pressure of 153.9 +/- 26.9 and 106.9 +/- 9.1 mm Hg respectively, it has been observed that in hypertensive platelets there was a marked decrease in 5-HT uptake and content, an increase in 5-HT efflux and an accompanying increase in Plasma 5-HT and 5-HIAA levels. Regression analysis of the data indicated a significant correlation between rise in diastolic blood pressure and these changes in 5-HT kinetics.     

Effects of naloxone on regional blood flow distribution in canine hemorrhagic shock

The opiate antagonist naloxone increases arterial pressure, maximal left ventricular dp/dt and cardiac output when administered to dogs subjected to hemorrhagic shock. The purpose of this study was to investigate regional blood flow changes associated with naloxone treatment in anesthetized hypovolemic and normovolemic dogs. Hypovolemic dogs (n = 10) were bled over 30 min (t = -30 to t = 0) to a pressure of 45 mm Hg which was maintained for 1 hr. At t = 60, five dogs received naloxone (2 mg/kg + 2 mg/kg X hr), and five received an equal volume of saline. Regional blood flows were determined at t = -30, 45, and 90 min using 15-micron microspheres. Normovolemic dogs (n = 10) were subjected to the same protocol except they were not bled. During hypovolemia, naloxone produced significant increases in myocardial, intestinal, hepatic, and adrenal blood flows whereas saline treatment did not. No significant changes in skin, muscle, fat, pancreatic, renal, or brain flows were detected. The increases in blood flow were not associated with significant changes in vascular resistance. Naloxone had no significant effects on any hemodynamic parameter during normovolemia. The beneficial effects of naloxone in hemorrhagic shock include increased blood flow to vital organs due to increased perfusion pressure which is secondary to improved cardiac performance.     

Seasonal variation of cardiovascular function in the marmot, Marmota flaviventris

Monthly measurements of heart rate, mean arterial pressure, and cardiac output were made on active and hibernating marmots from the time of emergence from hibernation through the next hibernation period. From these measurements cardiac index, stroke index, and total peripheral resistance were calculated on the basis of estimated lean body mass. Heart rate was low after emergence (132 +/- 9.5 beats (B)/min), peaked in August (160 +/- 9.3 B/min), and then fell slightly in September and October. During hibernation heart rate fell to 9 +/- 1.1 B/min. Mean arterial pressure, which was low in early spring (101 +/- 6.9 mm Hg), rose to a peak value in June (131 +/- 7.7 mm Hg) and remained essentially unchanged until hibernation when it fell to 52 +/- 4.0 mm Hg. Cardiac index (61 +/- 4.9 ml/kg min) in March rose to a peak in May (83 +/- 8.5 ml/kg min) and fell linearly until October. There was an additional drop in cardiac index during hibernation (7.6 +/- 0.9 ml/kg min). Total peripheral resistance increased linearly from the time of emergence until October. Most of this change was due to the decrease in cardiac index. Stroke index showed no significant changes in the prehibernation period, but increased by 55% during hibernation. Maintenance of arterial pressure in the months preceding hibernation in the face of diminishing cardiac index indicate that alterations in vasomotor tone or shifts in patterns of blood flow occurred prior to the hibernation period.     

Case-control study of stroke and the quality of hypertension control in north west England.

OBJECTIVE: To examine the risk of stroke in relation to quality of hypertension control in routine general practice across an entire health district. DESIGN: Population based matched case-control study. SETTING: East Lancashire Health District with a participating population of 388,821 aged < or = 80. SUBJECTS: Cases were patients under 80 with their first stroke identified from a population based stroke register between 1 July 1994 and 30 June 1995. For each case two controls matched with the case for age and sex were selected from the same practice register. Hypertension was defined as systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 95 mm Hg, or both, on at least two occasions within any three month period or any history of treatment with antihypertensive drugs. MAIN OUTCOME MEASURES: Prevalence of hypertension and quality of control of hypertension assessed by using the mean blood pressure recorded before stroke) and odds ratios of stroke (derived from conditional logistic regression). RESULTS: Records of 267 cases and 534 controls were examined; 61% and 42% of these subjects respectively were hypertensive. Compared with non-hypertensive subjects hypertensive patients receiving treatment whose average pre-event systolic blood pressure was controlled to < 140 mm Hg had an adjusted odds ratio for stroke of 1.3 (95% confidence interval 0.6 to 2.7). Those fairly well controlled (140-149 mm Hg), moderately controlled (150-159 mm Hg), or poorly controlled (> or = 160 mm Hg) or untreated had progressively raised odds ratios of 1.6, 2.2, 3.2, and 3.5 respectively. Results for diastolic pressure were similar; both were independent of initial pressures before treatment. Around 21% of strokes were thus attributable to inadequate control with treatment, or 46 first events yearly per 100,000 population aged 40-79. CONCLUSIONS: Risk of stroke was clearly related to quality of control of blood pressure with treatment. In routine practice consistent control of blood pressure to below 150/90 mm Hg seems to be required for optimal stroke prevention.     

Reference cardiopulmonary values in normal dogs

The purpose of this project was to collate canine cardiopulmonary measurements from published and unpublished studies in our laboratory in 97 instrumented, unsedated, normovolemic dogs. Body weight; arterial and mixed-venous pH and blood gases; mean arterial, pulmonary arterial, pulmonary artery occlusion, and central venous blood pressures; cardiac output; heart rate; hemoglobin; and core temperature were measured. Body surface area; bicarbonate concentration; base deficit; cardiac index; stroke volume index, systemic and pulmonary vascular resistance indices; left and right cardiac work indices; alveolar partial pressure of oxygen (pO2) ; alveolar-arterial pO2 gradient (A-apO2); arterial, mixed-venous, and pulmonary capillary oxygen content; oxygen delivery; oxygen consumption; oxygen extraction; venous admixture; arterial and mixed-venous blood CO2 contents; and CO2 production were calculated. In the 97 normal, resting dogs, mean arterial and mixed-venous pH were 7.38 and 7.36, respectively; partial pressure of carbon dioxide (pCO2), 40.2 and 44.1 mm Hg, respectively; base-deficit, -2.1 and -1.9 mEq/liter, respectively; pO2, 99.5 and 49.3 mm Hg, respectively; oxygen content, 17.8 and 14.2 ml/dl, respectively; A-a pO2 was 6.3 mm Hg; and venous admixture was 3.6%. The mean arterial blood pressure (ABPm), mean pulmonary arterial blood pressure (PAPm), pulmonary artery occlusion pressure (PAOP) were 103, 14, and 5.5 mm Hg, respectively; heart rate was 87 beats/min; cardiac index (CI) was 4.42 liters/min/m2; systemic and pulmonary vascular resistances were 1931 and 194 dynes.sec.cm-5, respectively; oxygen delivery, consumption and extraction were 790 and 164 ml/min/m2 and 20.5%, respectively. This study represents a collation of cardiopulmonary values obtained from a large number of dogs (97) from a single laboratory using the same measurement techniques.     

Glucocorticoids in blood pressure regulation

Glucocorticoid excess is associated with hypertension in man and in animals. This type of hypertension is of rapid onset and independent of salt intake; it can be inhibited by glucocorticoid antagonists, such as RU486. In normal rats, RU486 blunts vascular reactivity to norepinephrine and angiotensin II. In normal rats on low-salt diet, it induces a fall in blood pressure of approximately 20 mm Hg, due to decreased vascular resistance. This suggests that in some conditions, endogenous glucocorticoids contribute to the maintenance of blood pressure by enhancing vascular reactivity.     

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.     

Cardiovascular and biological effects of K+ channel openers, a class of drugs with vasorelaxant and cardioprotective properties

Several new chemical entities (RP 52891, cromakalim and its derivatives) are potent and specific openers of vascular K+ channels. This mechanism is also shared, at least partially, by drugs such as minoxidil, diazoxide, pinacidil and nicorandil. The opening of plasmalemma K+ channels produces loss of cytosolic K+. This effect results in cellular hyperpolarization and functional vasorelaxation. In normotensive or hypertensive rats, K+ channel activators decrease aortic blood pressure (by producing a directly mediated fall in systemic vascular resistance) and reflexly increase heart rate. The former effect is not modified by specific blockers of classical vascular receptors but it is completely antagonized by the hypoglycemic sulphonylurea, glibenclamide, an established blocker of ATP-regulated K+ channels. K+ channel openers produce selective coronary vasodilatation and afford functional and biochemical protection to the ischemic myocardium. This salutary effect is mediated via cardiac K+ channel modulation and may result from an improved myocardial oxygen balance in the ischemic region. K+ channel openers increase plasma renin activity in animals as well as in man. However, only diazoxide, but not cromakalim or RP 52891, lowers plasma insulin concentration. The dose of glibenclamide entirely blocking the latter effect is over 50-fold smaller than that antagonizing the hypotensive and hyper-reninemic responses to diazoxide. In conclusion, K+ channel activators are potent vasorelaxant and cardioprotective agents possessing an original mechanism of action which is the opening of plasmalemma ATP-regulated K+ channels. Their clinical use as antihypertensive agents may be accompanied by undesirable effects (characteristic of peripheral vasodilators) which are likely to be attenuated or avoided by controlled release formulations. However, inasmuch as low doses of K+ channel openers may be sufficient to produce selective coronary artery dilatation and cardioprotection, these compounds could be of particular value in treating patients with coronary artery disease efficaciously and possibly without adverse cardiovascular effects.     

Hormonal mechanisms in the regulation of arterial pressure and its hemodynamic structure in old age

Age-related increase of vascular resistance determines blood pressure (BP) level in normotensive and hypertensive people. Maintenance of normotension in old age is connected with a decrease of the cardiac output. Increased cardiac output is considered to be an important factor of arterial hypertension in old age. Disturbances in renin-angiotensin-aldosterone and hypophyseal-adrenal systems are observed with advanced age and their degree increases in arterial hypertension. Variability of BP within normal range is closely connected with plasma aldosterone and cortisol concentrations. BP level and increased cardiac output are related to increased plasma ACTH and vasopressin concentrations in hypertensive subjects.     

Reductions in blood pressure after acute exercise by hypertensive rats

Postexercise reductions in blood pressure at rest have been reported for hypertensive subjects. To determine whether post-exercise hypotension would occur in spontaneously hypertensive rats and to test the hypothesis that any reductions would result because of decreases in regional vascular resistances, hypertensive rats (n = 19) were instrumented with indwelling arterial catheters and Doppler probes to measure regional blood flows from the iliac, superior mesenteric, and renal arteries. Data were collected from animals who performed a 20- and a 40-min treadmill test at between 60 and 70% of their maximum O2 uptake. When the animals ran for 20 min, there was a pre- to postexercise drop in mean arterial pressure (MAP) from 158 +/- 3.6 to 150 +/- 3.6 mmHg (P less than 0.05), which was recorded 30 min after the exercise had ceased. The pre- to postexercise reduction in MAP after 40 min of treadmill running was from 154 +/- 3.1 to 138 +/- 3.0 mmHg (P less than 0.05) as recorded 30 min postexercise. Postexercise heart rate was significantly lower after the 40-min exercise bout, from a preexercise mean of 351 +/- 3 beats/min to 324 +/- 5 beats/min 30 min after the treadmill had stopped. Surprisingly, marked pre- to postexercise reductions in regional vascular resistance were not observed in either the iliac, superior mesenteric, or renal vascular beds. These data demonstrated the existence of postexercise hypotension in genetic hypertensive rats and suggested that reductions in cardiac output were the primary hemodynamic mechanism for this finding.