Angiotensin II Type 1 Receptor mRNA Levels in the Brains of Normotensive and Spontaneously Hypertensive Rats

Abstract: The type 1 angiotensin II (All) receptor (AT₁-R) has been implicated in the physiological actions mediated by All in the brain. In view of the reported hyperactivity of the brain All system in the spontaneously hypertensive rat (SHR), we compared the expression of AT,-R mRNAs in the brains of normotensive [Wistar Kyoto (WKY)] and SHR animals. Northern blot analysis showed about three- and ∼20-fold increases in the levels of AT₁-R mRNAs from the hypothalamus and brainstem areas, respectively, of the SHR compared with the WKY rat brain. This was attributable to greater levels of both AT,_1A- and AT,_1B-R mRNA subtypes in these areas from the SHR. These observations suggest that increased All receptor levels in SHR brain may, in part, be a result of increased expression of the AT₁-R gene.     

Risk Factors of Cardiovascular Diseases and the Capillary Endothelium in Subjects with Different Levels of Normal Blood Pressure

The capillary circulation in the forearm and crus was studied by occlusion plethysmography at rest and upon stimulation with nitric oxide during reactive hyperemia in 249 virtually healthy subjects with different levels of arterial blood pressure lower than 140/90 mm Hg. Specific features of the microcirculation were found in the forearm and crus depending on the blood pressure level. An increase in the blood pressure higher than 120/80 mm Hg was associated with an increased adverse effect of integral risk factors and heredity on parameters of the capillary circulation, especially in women.     

Valuation of Normal Range of Ankle Systolic Blood Pressure in Subjects with Normal Arm Systolic Blood Pressure

Subject

This study aimed to establish a normal range for ankle systolic blood pressure (SBP).

Methods

A total of 948 subjects who had normal brachial SBP (90-139 mmHg) at investigation were enrolled. Supine BP of four limbs was simultaneously measured using four automatic BP measurement devices. The ankle-arm difference (An-a) on SBP of both sides was calculated. Two methods were used for establishing normal range of ankle SBP: the 99% method was decided on the 99% reference range of actual ankle BP, and the An-a method was the sum of An-a and the low or up limits of normal arm SBP (90–139mmHg).

Results

Whether in the right or left side, the ankle SBP was significantly higher than the arm SBP (right: 137.1±16.9 vs 119.7±11.4 mmHg, P<0.05). Based on the 99% method, the normal range of ankle SBP was 94~181 mmHg for the total population, 84~166 mmHg for the young (18–44 y), 107~176 mmHg for the middle-aged(45–59 y) and 113~179 mmHg for the elderly (≥60y) group. As the An-a on SBP was 13mmHg in the young group and 20mmHg in both middle-aged and elderly groups, the normal range of ankle SBP on the An-a method was 103–153 mmHg for young and 110–160 mmHg for middle-elderly subjects.

Conclusion

A primary reference for normal ankle SBP was suggested as 100-165 mmHg in the young and 110-170 mmHg in the middle-elderly subjects.     

Administration-Time-Dependent Effects of Doxazosin GITS on Ambulatory Blood Pressure of Hypertensive Subjects

Previous studies have shown that a single nighttime dose of standard doxazosin, an α-adrenergic antagonist, reduces blood pressure (BP) throughout the 24 h. We investigated the administration-time-dependent effects of the new doxazosin gastrointestinal therapeutic system (GITS) formulation. We studied 91 subjects (49 men and 42 women), 56.7 ± 11.2 (mean ± SD) yrs of age with grade 1–2 essential hypertension; 39 patients had been previously untreated, and the remaining 52 had been treated with two antihypertensive medications with inadequate control of their hypertension. The subjects of the two groups, the monotherapy and polytherapy groups, respectively, were randomly assigned to receive the single daily dose of doxazosin GITS (4 mg/day) either upon awakening or at bedtime. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours just before and after 3 months of treatment. After 3 months of doxazosin GITS therapy upon awakening, there was a small and nonstatistically significant reduction in BP (1.8 and 3.2 mm Hg in the 24 h mean of systolic and diastolic BP in monotherapy; 2.2 and 1.9 mm Hg in polytherapy), mainly because of absence of any effect on nocturnal BP. The 24 h mean BP reduction was larger and statistically significant (6.9 and 5.9 mm for systolic and diastolic BP, respectively, in monotherapy; 5.3 and 4.5 mm Hg in polytherapy) when doxazosin GITS was scheduled at bedtime. This BP-lowering effect was similar during both the day and nighttime hours. Doxazosin GITS ingested daily on awakening failed to provide full 24 h therapeutic coverage. Bedtime dosing with doxazosin GITS, however, significantly reduced BP throughout the 24 h both when used as a monotherapy and when used in combination with other antihypertensive pharmacotherapy. Knowledge of the chronopharmacology of doxazosin GITS is key to optimizing the efficiency of its BP-lowering effect, and this must be taken into consideration when prescribing this medication to patients.     

Effect of Vegetarianism and Smoking on Vitamin B12, Thiocyanate,and Folate Levels in the Blood of Normal Subjects

Vitamin B₁₂, thiocyanate, and folate levels in the blood were estimated in 69 apparently normal subjects, of whom 26 were non-vegetarian non-smokers, 19 non-vegetarian smokers, 15 vegetarian non-smokers, and nine vegetarian smokers. The serum total (cyanide-extracted) B₁₂ level (value A) ranged from 105 to 728 pg/ml, with a mean of 292 pg/ml. The highest values were found in non-vegetarian non-smokers and the lowest in vegetarian smokers. There was no significant difference in value A between smokers as a group and non-smokers as a group. On the other hand, in vegetarians value A was very significantly lower than in non-vegetarians regardless of their smoking habits.It is suggested that A may represent both the protein-bound and free forms of vitamin B₁₂ in the blood, and B mainly the free B₁₂, which may be the physiologically active form. The plasma thiocyanate level varied from 1·0 to 15 μmol/100 ml, being, as expected, much higher in smokers (mean 8·20 μmol/100 ml) than in non-smokers (mean 2·02 μmol/100 ml). There was a rough correlation between falling B₁₂ levels and rising thiocyanate levels. The serum folate level ranged from 2·75 to 15·75 ng/ml, and was slightly but significantly higher in vegetarians (mean 6·60 ng/ml) than in non-vegetarians (mean 4·79 ng/ml), reflecting the greater content of folate in a vegetarian diet.     

The Relationship Between Serum Calcium Level, Blood Lipids, and Blood Pressure in Hypertensive and Normotensive Subjects who Come from a Normal University in East of China

Previous studies revealed that low calcium intake is related to high prevalence of cardiovascular diseases such as hypertension. However, the relationship between serum calcium and blood pressure was unclear. The prevalence of hypertension is high in China. Thus, the aim of this study was to evaluate the serum calcium level between hypertensive and normotensive groups and to investigate the correlation between serum calcium, blood pressure, and blood lipid parameters. A total of 1,135 adult subjects participated in this study and were divide into two study groups: a hypertensive group (n?=?316) who had 140 mmHg or higher in systolic blood pressure (SBP) or 90 mmHg or higher in diastolic blood pressure (DBP) and an age- and sex-matched normotensive group (n?=?819, 120 mmHg or less SBP and 80 mmHg or less DBP). Our results indicate a significant trend for men (60 years old or older) in the direction of decreasing blood pressure with increasing serum calcium level, but no trend for women was indicated. In the normotensive group, a significant positive correlation was found between DBP and total cholesterol (P?<?0.01) and triglyceride (P?<?0.01), Likewise, triglyceride was positively correlated with SBP (P?<?0.01). Overall, these data suggest that serum calcium may have an influence in the blood pressure of older male subjects with hypertension and in blood lipid profiles of normotensive subjects.     

Tooth Element Levels Indicating Exposure Profiles in Diabetic and Hypertensive Subjects from Mysore,India

Element contents of teeth elucidate exposure nature, but less is known about association of tooth element concentrations of diabetics and hypertensives with exposure profile. Present study aims to estimate copper, chromium, iron, zinc, nickel, and lead concentrations in the permanent teeth of control, diabetic, and hypertensive subjects from Mysore. The results show that lead levels of teeth (Pb-T) are higher in the hypertensives and diabetics, whereas copper levels of teeth (Cu-T) are lower in the hypertensives and users of stainless steel utensils than that of controls and users of mixed utensils. The elevated Cu-T levels found in the users of mixed utensils that being made of several metals are ascribed to leaching effect of sour and spicy food of Indian cuisine. The element levels were influenced by diet (Zn-T), place of living, sex and income (Pb-T) of the subjects, but not by age, drinking water from different sources, and certain habits viz., smoking, alcohol consumption, chewing betel, and nut. Thus, it is evident that high Pb-T and low Cu-T levels may be related with diabetes and hypertension and high Pb-T and Cu-T levels, respectively, in the urbanites, and the users of mixed utensils may show different exposure profiles from environment and utensils.     

Angiotensin and Cerebral Blood Flow

1.General properties of the cerebral circulation.2.Cerebral blood flow autoregulation in hypertension, in stroke, and during the aging process.3.The Angiotensin system.4.Angiotensin receptor subtypes.5.Angiotensin receptors and actions of Angiotensin II in the brain: interactions between the brain and circulating Angiotensin II.6.The cerebrovascular Angiotensin system.7.Effects of Angiotensin II on cerebrovascular reactivity.8.Angiotensin and cerebrovascular flow.9.Effects of therapeutic modulation of the Angiotensin II system on cerebrovascular regulation in health and disease.10.Conclusions.     

Effects of Losartan/Hydrochlorothiazide on Serum Uric Acid Levels and Blood Pressure in Hypertensive Patients

The effect of a mixed formulation of 50 mg losartan (LOS) and 12.5 mg hydrochlorothiazide (HCTZ) on blood pressure and the uric acid metabolism was analyzed in 73 patients who switched to this formulation from other antihypertensive drugs. Eight patients who switched to the formulation from the regular dose of renin-angiotensin (RA) inhibitor (angiotensin receptor blocker [ARB] or angiotensin-converting enzyme [ACE] inhibitor) only showed a significant decrease in blood pressure, from 156.9 ± 14.1/88.6 ± 9.7 mmHg to 128.3 ± 16.0/76.1 ±10.7 mmHg (p = 0.007), and a significant increase in serum uric acid levels, from 5.2 ± 1.1 mg/dL to 6.8 ± 0.7 mg/dL (p = 0.02). In the other 50 patients who switched from a combination of the regular dose of RA inhibitor and calcium channel blocker (CCB), their blood pressure significantly increased, from 126.0 ± 13.8/72.0 ± 10.0 mmHg to 132.5 ± 16.4/76.5 ± 11.3 mmHg (p = 0.02), and their serum uric acid levels also significantly increased, from 5.6 ± 1.1 mg/dL to 6.1 ± 1.3 mg/dL (p = 0.0002). Considering that guidelines recommend using antihypertensive therapies that do not lead to an increase in serum uric acid levels, we conclude that using the ARB/HCTZ combination is less suitable than the regular dose of the ARB/CCB combination due to its effect on hypertension and serum uric acid levels.     

Phenformin-induced Hypoglycaemia in Normal Subjects

Study of the effect of phenformin on the blood glucose level in normal subjects before and during 70 hours of starvation showed a statistically significant hypoglycaemic effect after 40 hours of starvation. This effect was not due to increased glucose utilization.Another finding in this study was a statistically significant decrease in total urinary nitrogen excretion during starvation in subjects given phenformin. These findings show that the hypoglycaemic effect of phenformin in starved normal subjects is due to inhibition of gluconeogenesis.     

Excessive Zinc Intake Increases Systemic Blood Pressure and Reduces Renal Blood Flow via Kidney Angiotensin II in Rats

This study investigated the effects of excess zinc intake on the mean arterial pressure (MAP), renal blood flow (RBF), inulin clearance (IC), serum zinc level, serum angiotensin-converting enzyme (ACE) activity, and kidney angiotensin II (AT II) levels in rats. Experiments were performed on male Sprague?CDawley rats maintained for 4?weeks on a diet containing either 5?mg/100?g (control group), 50?mg/100?g (Zn50 group), or 200?mg/100?g (Zn200 group) zinc carbonate. Serum zinc levels significantly increased to 126.5?% in the Zn50 group and 198.1?% in the Zn200 group compared with controls. MAP significantly increased to 107.8?% in the Zn50 group and 114.5?% in the Zn200 group again compared with controls. Although the difference in serum ACE activity was independent of the serum zinc levels, the kidney AT II levels increased significantly to 137.2?% in the Zn50 group and 174.4?% in the Zn200 group compared with the controls. RBF was decreased significantly to 74.4?% in the Zn50 group and 69.7?% in the Zn200 group compared with the controls. IC values were significantly decreased to 69.6?% in the Zn50 group and 52.7?% in the Zn200 group as compared with control levels. Combined together, these results show that excessive Zn intake reduced IC and RBF and increased MAP and kidney AT II levels, suggesting that excessive Zn intake reduces renal function.     

Decrease in Blood Pressure and Regression of Cardiovascular Complications by Angiotensin II Vaccine in Mice

Vaccines have been recently developed to treat various diseases such as cancer, rheumatoid arthritis and Alzheimer’s disease in addition to infectious diseases. However, before use in the clinical setting, vaccines targeting self-antigens must be demonstrated to be effective and safe, evoking an adequate humoral immune response from B cells while avoiding T cell activation in response to self. Although the vaccine targeting angiotensin II (Ang II) is efficient in rodents and humans, little is known regarding the immunological activation and safety of the vaccine. In this study, we evaluated the efficiency and safety of an Ang II peptide vaccine in mice. Immunization with Ang II conjugated to keyhole limpet hemocyanin (KLH) successfully induced the production of anti-Ang II antibody, which blocked Ang II signaling in human aortic smooth muscle cells. However, Ang II itself did not activate T cells, as assessed by the proliferation and lymphokine production of T cells in immunized mice, whereas KLH activated T cells. In an Ang II-infused model, the non-immunized mice showed high blood pressure (BP), whereas the immunized mice (Ang II-KLH) showed a significant decrease in systolic BP, accompanied by significant reductions in cardiac hypertrophy and fibrosis. Importantly, anti-Ang II antibody titer was not elevated even after the administration of large amounts of Ang II, indicating that Ang II itself boosted antibody production, most likely due to less activation of T cells. In addition, no accumulation of inflammatory cells was observed in immunized mice, because endogenous Ang II would not activate T cells after immunization with Ang II-KLH. Taken together, these data indicate that vaccines targeting Ang II might be effective to decrease high BP and prevent cardiovascular complications without severe side effects.