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

Atrial natriuretic peptide (alpha-hANP-99-126), 1 x 10(-8) to 5 x 10(-10) M was able to further relax the non-contracted aortic smooth muscle of rabbit after complete recovery from a previous challenge with human angiotensin II (AII), 1 x 10(-6) M. The relaxation was directly proportional to the response of the ring or strip to the previous challenge with AII. ANP does not have effect on basal tension in isolated strips or rings of the rabbit aorta not previously exposed to AII. Norepinephrine (NE), 10(-7) M was less potent in inducing reactivity of the vessel to ANP, ie, only a small relaxant effect on basal tension could be observed. A similar vasorelaxant effect of ANP on basal tension could be obtained in the absence of extracellular calcium: Ca(2+)-free Ringers' solution containing 2 mM ethylene-glycol-bis (beta-aminoethyl ether)N',N' tetraacetic acid (EGTA-Ringer). In contrast, sodium nitroprusside 10(-8) M does not affect basal tension. Present results demonstrate the role of the physiological state of the vessel in the reactivity to ANP.

The acute sensitivity to sodium loading has been investigated in 26 borderline hypertensive patients (BHT) undergoing acute i.v. NaCl infusion. Measurements included blood pressure (BP), forearm vascular resistance (FVR) and venous distensibility (VV30), plasma renin activity (PRA), plasma aldosterone, plasma atrial natriuretic factor (ANF), and plasma levels of endogenous Na+/K+ATPase inhibitor. Sodium loading was associated with a greater than 8% increase in mean BP in 12 patients defined as salt-sensitive (NaCl-SENS) in comparison to salt-insensitive (NaCl-INSENS) subset. NaCl-SENS patients in comparison to NaCl-INSENS exhibited 1) a greater baseline VV30 (2.1 vs 1.4 ml/100 ml; p less than .005), and a response to saline characterized by 2) increased FVR (21.4 vs -6.5%; p less than .005), 3) blunted PRA suppression (-42 vs -67%; p less than .05), 4) delayed ANF response and 5) release of a Na+/K+ATPase inhibitor. Post-loading cumulative urinary sodium excretion was reduced in NaCl-SENS borderline hypertensives compared to NaCl-INSENS (2.6 vs 3.8 mumol/min/Kg; p less than .05). We conclude that acute salt-sensitivity in BHT is characterized by a blunted hormonal response to sodium loading which could be responsible of the activation of hemodynamic as well as humoral mechanisms leading to progressive blood pressure increase.

The effects immobilization stress on renal sympathetic neurotransmission as well as on heart, spleen and adrenal catecholamine content were examined in the rat. A single 2.5 hr stress period produced significant increases in blood pressure, heart rate, plasma norepinephrine and plasma epinephrine concentrations. However, no changes in renal catecholamine content or in stimulus-induced (1 Hz, 120 pulses, supramax. V) overflow of catecholamines were observed when the isolated perfused rat kidney was studied immediately after the 2.5 hr stress period. In contrast, the single stress period produced a 3-4 fold increase in cardiac epinephrine content while no effects on spleen or adrenal catecholamine content were observed. When stress was applied for 7 daily 2.5 hr periods, the repetition of the stress failed to produce any changes in renal neurotransmitter content or stimulus-induced overflow from the isolated perfused rat kidney. The data suggest that the accumulation of epinephrine into peripheral sympathetic nerves as a result of stress-induced adrenal catecholamine release is not a phenomenon which can be generalized to all regions of the cardiovascular system.

The influence that centrally administered angiotensin-II (ANG-II) and saralasin (SAR) has on renal norepinephrine secretion rate (NESR) and renal renin secretion rate (RSR) were studied. Rats were given thermal lesions of the medial basal forebrain (MBF) or sham surgery. Twenty-four hours later the right kidney was vascularly isolated (but neurally intact) and perfused with an artificial plasma at either a constant pressure (100 mm Hg) or constant flow (600 microliters/min). Renal perfusate was collected before (pre-injection) and at 10 min intervals after central administration of peptides for determination of NESR and RSR. In both perfusion models, intracerebroventricular (ICV) ANG-II increased renal NESR. In MBF lesioned rats pre-injection renal NESR is reduced and the response to ICV ANG-II is blocked. In both perfusion models ICV ANG-II decreases renal RSR. Concomitant administration of SAR blocks the effect of ANG-II on both NESR and RSR. MBF lesioned rats had significantly elevated pre-injection levels of RSR and there is no change in RSR following ICV ANG-II. These experiments indicate that centrally administered ANG-II increases renal NESR concomitant with a decrease in renal RSR and that MBF lesions block those changes.

An enzyme linked immunosorbent assay for rat angiotensinogen was developed based on one monoclonal antibody with high affinity for angiotensinogen and des-angiotensin 1-angiotensinogen and rabbit polyclonal antibodies for angiotensinogen was developed. Serum levels of angiotensinogen were lower in female than in male rats but increased significantly after hypophysectomy. Estrogen substitution after hypophysectomy had no further stimulatory or inhibitory influence. In hypophysectomized animals continuous and intermittent growth hormone administration had clearly different effects. The results indicate that the sexually dimorphic secretion of growth hormone is involved in the regulation of circulating angiotensinogen concentrations in the rat.

The present studies examine the effect of gonadal hormones on the development of hypertension in Dahl salt-sensitive rats fed a high salt diet. In the first study, administration of estradiol benzoate did not prevent hypertension in either adult ovariectomized females or intact males. In a second study, neonatal castration of males slowed the onset of salt-induced hypertension, and females that were treated neonatally with testosterone developed somewhat higher pressures that did untreated females. These data extend to Dahl S rats the findings observed originally in spontaneously hypertensive rats that blood pressure is modulated by gonadal hormones. These results are consistent with the conclusion that gonadal hormones may exert organizational effects on cardiovascular control regions of the brain during early postnatal development in rats.

Left ventricular hypertrophy (LVH) is an independent risk indicator of cardiovascular disease. Obtaining reversal of hypertension-induced cardiac hypertrophy seems to be a desirable objective of antihypertensive treatment. A total of 2,357 patients were included in a meta-analysis on the effect of antihypertensive pharmacological therapy on LVH. Overall left ventricular mass (LVM) was reduced by 11.9% (95% confidence interval (CI) 10.1-13.7) in parallel with a reduction of mean arterial pressure of 14.9% (CI 14.0 to 15.8). When evaluating the effect of first-line therapies on calculated LVM using the same formula for all studies, the absolute reductions in g were 44.7 (ACE-inhibitors), 22.8 (beta-blockers), 26.9 (calcium antagonists) and 21.4 (diuretics) when adjusted for differences between studies (ANCOVA). It can be concluded that effective antihypertensive therapy reduces LVM. ACE-inhibitors, beta-blockers and calcium antagonists reduce LVM by reducing wall hypertrophy, the effect of ACE-inhibitors being the most pronounced. Diuretics reduce LVM mainly through an effect on left ventricular inner diameter. How these effects affect prognosis is still an open question.

Aim of the study was to evaluate the effect of cardiopulmonary receptors activation and deactivation on antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) incretion in hypertensive and normotensive subjects. Twenty-one male subjects, 7 normotensives and 14 mild hypertensives, 7 without and 7 with left ventricular hypertrophy (LVH) were admitted to the study. Each subject underwent selective loading and unloading of cardiopulmonary receptors, by application of a positive (LBPP) or negative (LBNP) pressure to the lower body. Blood samples were taken for measurement of ANP, ADH, PRA, immunoreactive renin, aldosterone, noradrenaline and adrenaline. ADH plasma concentration increased during cardiopulmonary receptors inhibition, but this increase became statistically significant (p less than 0.05) at a step of LBNP (-40 mm Hg), in which an involvement of the sinoaortic receptors cannot be excluded. ANP plasma levels increased progressively during LBPP (p less than 0.05 at least). These changes were significantly reduced in hypertensive patients with LVH.

Circadian blood pressure (BP) variation were studied in patients with renovascular hypertension (RVH) and primary aldosteronism (PA). Ambulatory BP (ABP) was monitored every 5 min for 24 hrs in a ward setting in 23 patients with PA and 17 patients with RVH (13 patients with unilateral renal arterial stenosis and 4 with bilateral stenosis). In patients with RVH, ABP was monitored before and after treatment with a converting enzyme inhibitor or percutaneous transluminal angioplasty. Plasma renin activity (PRA) was high before percutaneous transluminal angioplasty in almost all patients with RVH and low in those with PA. Ordinary circadian BP variation, i.e. nocturnal fall and diurnal rise in BP, was confirmed in the patients with unilateral or bilateral renal artery stenosis. Percutaneous transluminal angioplasty successfully normalized both BP and PRA in those with RVH. Normal circadian BP variation was observed in those with RVH before the treatment with a converting enzyme inhibitor or percutaneous transluminal angioplasty as well as during treatment with the former and after treatment with the latter. Circadian BP variation in the patients with RVH was affected by the pathogenesis of renal artery stenosis alone, i.e, fibromuscular hyperplasia and atherosclerosis; with fibromuscular hyperplasia normal circadian BP variation was observed, while with atherosclerosis, nocturnal BP fall was restricted or eliminated. Circadian BP variation in those with PA before and after excision of adrenal adenoma was essentially similar to that in normal subjects and essential hypertensive patients. From these it seems that in patients with RVH or PA, circadian BP variation is not affected by hypertension per se or by pathogenesis of hypertension.

The present study investigated the role of ouabain-dependent inhibition of the Na(+)-K+ pump and stimulation of the brain renin-angiotensin system by looking at 1) the short-term and long-term effects of ouabain on arterial blood pressure, and 2) the acute and chronic effects of angiotensin II (ANG II) intraventricularly (i.c.v.) on the release of an endogenous inhibitor of the Na(+)-K+ pump. Ouabain infused subcutaneously in a dose of 1.5 mg.kg-1. 24 h-1 for 7 days did not affect arterial blood pressure in rats, whereas increases in both blood pressure and weight were observed in rats infused with ouabain at the same dose for a 4-week period. Plasma supernate obtained from pentobarbital-anesthetized dogs acutely treated with ANG II (1 microgram i.c.v. every 30 min for 2 h) induced a 44% decrease in the ouabain-sensitive 86Rb uptake by the rat tail artery which was prevented by pretreatment with saralasin i.c.v. Plasma supernate obtained from dogs that were infused for 4 days with ANG II (20 ng/min i.c.v.) and received saline as the drinking fluid also reduced by 34% the ouabain-sensitive 86Rb uptake by the rat tail artery. The present study provides evidence that chronic inhibition of the Na(+)-K+ pump for 4 weeks leads to the development of hypertension and that the release of an endogenous inhibitor of the Na(+)-K+ pump is implicated in the hypertension resulting from chronic stimulation of the brain angiotensin-system and an increase in sodium chloride intake.