Clinical and experimental hypertension. Part A, Theory and practice最新文献

In conscious and anaesthetized rats the baroreceptor heart reflex (BHR) was checked before and after i.c.v. application of isotonic or hypertonic (0.6 M; 1.0 M) NaCl solution, artificial cerebrospinal fluid (aCSF) and 1.0 M mannitol solution. The BHR was tested by evaluating the alteration of the inter-beat interval (IBI) in response to an artificial BP rise or drop which had been evoked by i.v. bolus injection of either phenylephrine or sodium nitroprusside. The slope of the correlation function was taken to index the reflex sensitivity. In anaesthetized rats the mean sensitivity of the BHR was 0.6 ms/mm Hg (phenylephrine). l.c.v. administration of isotonic NaCl solution did not change BP, IBI or the BHR sensitivity, whilst i.c.v. infusion of hypertonic NaCl solution increased BP and shortened IBI. The BHR sensitivity was impaired only when 1.0 M NaCl solution was i.c.v. infused by 0.23 ms/mm Hg. In conscious rats the mean sensitivity of the BHR was 1.14 ms/mm Hg (phenylephrine) and 1.35 ms/mm Hg (sodium nitroprusside). In the conscious rats i.c.v. bolus injection of hypertonic NaCl solution increased BP as in anaesthetized rats, however, the IBI was prolonged, whilst 1.0 M mannitol solution and aCSF were without any influence on BP, IBI and BHR. l.c.v. administration of hypertonic NaCl solution reduced the BHR sensitivity by approximately 0.6 ms/mm Hg.

We performed renal function studies in dogs with chronic renovascular hypertension produced by complete occlusion of a renal artery. In addition, we evaluated in anesthetized dogs the acute effects of a novel angiotensin converting enzyme inhibitor, CGS 16,617, on renal function and plasma neurohormones (epinephrine, norepinephrine and vasopressin) 4 weeks after initiation of 2 kidney, 1 clip hypertension. CGS 16,617 effectively decreased blood pressure in renal hypertensive animals. This response was associated with suppression of angiotensin II indicating effective converting enzyme inhibition. In the non-clipped kidney, acute administration of CGS 16,617 increased effective renal plasma flow but not glomerular filtration rate and urinary sodium excretion. In the clipped kidney, CGS 16,617 caused no change in any parameter of renal function. Plasma norepinephrine, epinephrine and vasopressin were unaffected by administration of CGS 16,617. These studies showed that chronic occlusion of a renal artery does not result in renal infarction because of a compensatory increase in the amount of blood provided through capsular collateral vessels. The collateral circulation which has developed in the clipped kidney explains the lack of a converting enzyme inhibitor effect.

Despite the great therapeutic advances, the control of hypertension in populations is far below the achievable level, even in populations with highly developed health care. By the end of the 1980's, in selected European centres, 18-34% of cases of hypertension were undetected, and among those previously known, 22-38% were untreated. The cooperative WHO/WHL Hypertension Management Audit Project aimed at assessing some of the impediments to better control of hypertension. The concepts and attitudes of 2,215 physicians were surveyed. In various centres and at various patient ages, 25-45% of physicians would not start drug treatment below 100 mm Hg. When inquiring into the perceived reasons why hypertension had not been detected earlier, among other reasons, physicians tended to incriminate their workload, while patients often felt that there was a lack of interest on the doctor's part to take a blood pressure reading. In general, patient satisfaction seemed suboptimal. Physician's sources of information were varied; neither WHO, nor ISH or WHL seemed to play an important role in informing the physicians.

The concept of community intervention in the field of cardiovascular disease prevention was introduced in the late sixties and early seventies. The WHO European Collaborative Trial in the multifactorial prevention of coronary heart disease used communities (factories) in a traditional controlled trial. The intervention used in this trial was an extension of a medical care model with preventive elements. The first two major community intervention projects in CVD prevention--the North Karelia Project and the Stanford Heart Disease Prevention Programme--were the basis of further WHO and NHLBI coordinated projects. They have used community-based population-wide strategies including existing community leadership, social networks, mass campaigns and extensive direct education for the general population. In the evaluation of those projects quasi-experimental models are used because "perfect experiments" are not possible. Some projects have proven the feasibility of community intervention and its positive impact on lifestyles and cardiovascular risk factors in a whole population and that such a development is associated with reduced cardiovascular mortality rates.

In our study we tested firstly, whether BP changes induced by laboratory stress testing could be better related than resting blood pressure (BP) to hypertensive target-organ damage (TOD) and secondly, whether an exaggerated reactivity to stress testing might be associated with an increased prevalence of TOD. In 49 untreated essential hypertensives, BP measured at sitting rest and during a variety of stressful situations was related to the presence of TOD, assessed by electrocardiography (ECG) and fundoscopy examination. The degree of TOD was significantly correlated to resting SBP; neither SBP at peak of isometric or dynamic exercise, nor SBP during mental test showed a greater correlation with TOD than resting SBP (NS). A large variability of individual's level of BP reactivity across the different laboratory tests was observed. Patients were arbitrarily dichotomised into groups according to a hyperreactive or normoreactive response to each stress testing; patients classified as hyperreactive (SBP increase greater than upper 95% confidence limit) did not disclose a greater rate of cardiac and ocular damage than normoreactors (NS). In conclusion, stress BP does not increase the strength of relationship with TOD compared to resting BP. Cardiovascular reactivity differs according to the laboratory stimulus employed and an exaggerated BP rise during stress testing is not associated with an increased rate of TOD.

Renal nerve activity increases (Na+, K+)-ATPase activity and contributes to the development of hypertension in young SHR. The present study was designed to examine the effect of sodium intake on blood pressure and proximal tubule solute reabsorption in sham-operated or renal denervated, 5-week old SHR and WKY. Three-week old SHR and WKY rats underwent sham surgery or renal denervation with 10% phenol and were maintained for 10 days on either a 0.6% or 2.2% NaCl diet. Blood pressure was obtained by indirect tail cuff measurements during this interval. Of the eight groups, only sham-operated SHR on a high sodium diet had hypertension, 122.0 +/- 4.2 mm Hg vs. 98.7 +/- 3.3 mm Hg (mean for remaining groups). Renal plasma flow (RPF), glomerular filtration rate (GFR), and the fractional excretion of lithium (FELi) were determined in rats maintained on a 2.2% sodium diet at 5 weeks of age. FELi was less in sham-operated SHR, 5.3 +/- 0.7%, compared to WKY, 9.4 +/- 2.8% (P less than 0.02). Furthermore, denervation ameliorated the reduced FELi in SHR, 10.2 +/- 1.2%, without affecting FELi in WKY. RPF and GFR were similar between sham-operated and renal denervated SHR and WKY. No significant difference could be detected in net sodium balance between WKY and SHR during this period. These findings demonstrate 1) from the basis of FELi, young SHR, of this strain, exhibit enhanced proximal tubule solute reabsorption and hypertension while on a high sodium diet and, 2) renal denervation ameliorates both the enhanced proximal tubule solute reabsorption and the early development of hypertension. These data support the concept that renal nerve activity of young SHR is augmented and contributes to the development of hypertension by enhancing salt retention.

Rat renin cDNA was transfected into COS-7 and Chinese hamster ovary (CHO) cells and expressed under the control of the Simian Virus 40 early promoter. Conditioned media of the transfected cells showed renin activity only after trypsin treatment, suggesting prorenin was secreted into the medium. From the trypsinized serum-free culture of the transfected CHO cells active renin was purified to homogeneity by a simple three-step procedure. The active renin had similar specific activity, molecular weight, Km, pH optimum, and isoelectric point compared to native renin. The amino-terminal sequence was the same as that deduced from the renin cDNA. This suggests that the recombinant rat renin is similar to kidney renin in many respects, and is easily obtained by the present procedures.

The extent and duration of the blood pressure (BP) lowering effect of 20 mg nitrendipine (NIT) once daily and 40 mg nicardipine slow release (NIC) twice daily were compared in 12 men (aged 39-55 years) with mild essential hypertension according to a randomized, cross over study. Twenty-four-hour non invasive ambulatory BP monitoring (Spacelabs 5200) was performed at the end of a 2-week placebo run-in and after 4 weeks of each active treatment; automatic BP measurements were programmed at 15-min intervals. Both treatments significantly (p less than .01) reduced mean 24-hour and daytime systolic (SBP) and diastolic (DBP) BP, but had different effects on daytime BP profiles. NIT decreased SBP and DBP (p less than .05) in 5 out of 8 two-hour subperiods (from 8 a.m. to 6 p.m.), followed by a loss of effect; NIC reduced SBP and DBP (p less than .05) in 7 out of 8 two-hour subperiods (from 8 a.m. to 10 p.m.). During the night-time, NIT reduced mean SBP (p less than .05) and NIC both mean SBP and DBP values (p less than .05; p less than .05 vs NIT for SBP). Heart rate was not affected by either treatment. Thus, after short-term treatment in mild essential hypertensives nitrendipine once daily was not as effective as nicardipine slow release twice daily in reducing blood pressure throughout the 24 hours.

Synthetic sex steroid administration is a major cause of iatrogenic hypertension but little is known of the haemodynamic or metabolic consequences of these steroids. This study examined the short term blood pressure, volume and metabolic consequences of 5 day administration of synthetic androgen to normal men and synthetic oestrogen or progestogen to normal women. Healthy subjects (8 women, 6 men) on a constant diet took part in each of 3 studies. Males received testosterone undecanoate 120 mg/day (n = 6) and females either ethinyloestradiol 0.3 mg/day (n = 5) or norethisterone 15 mg/day (n = 6) for 5 days in the last week of the cycle. Norethisterone increased lying (+7 mmHg) and standing (+8 mmHg) systolic pressure but the other steroids did not alter blood pressure. All 3 treatments increased body weight. There were no consistent changes in plasma electrolytes or glucose with any steroid, and no urinary sodium retention or changes in urine Na:K ratio. Haematocrit fell on ethinyloestradiol but no steroid significantly increased plasma volume (measured as volume of distribution of 125I human serum albumin). Renin substrate and cortisol rose and renin concentration fell on ethinyloestradiol. These studies suggest that the progestogen component may contribute to the blood pressure raising effects of oral contraceptives.