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

The vasoconstrictor effects of endothelin-1 were studied in perfused mesenteric vascular beds (MVB) and aortic rings of 4-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Mean blood pressure (124 +/- 4 vs. 97 +/- 3 mmHg) and initial perfusion pressure in the MVBs (25 +/- 2 vs. 19.7 +/- 1.2) were significantly higher in SHR. Reactivity to endothelin-1 was increased in MVBs of SHR, as indicated by the maximum perfusion pressure obtained (223 +/- 8 vs 155 +/- 7 mmHg, p less than 0.001), whereas there was no significant difference in sensitivity between the two strains (EC50 values: 50 +/- 12 and 80 +/- 15 pmol, respectively). By contrast, in aortic rings reactivity and sensitivity to endothelin-1 were similar in both strains, (EC50s: 1.8 +/- 0.12 and 1.4 +/- 0.1 nM). Reactivity to norepinephrine was increased in MVBs, but reduced in aortic rings of SHR. The unchanged sensitivity to endothelin-1 and the unspecifically increased reactivity in the MVBs of SHR to endothelin-1 and norepinephrine indicate rather a change in vascular structure and not a functional abnormality. These results suggest that hyperreactivity to endothelin-1 may not be a primary hypertensive mechanism in genetic hypertension.

Retrospective analysis of hemodynamic factors was performed on hypertensive participants of our Multiple Risk Factor Intervention Trial (MRFIT) center to determine whether these may have a role in the higher mortality in a subgroup of special intervention (SI) participants with minor baseline electrocardiographic abnormalities. Stroke volume was estimated by a formula [SV = K(LVETxPP)x(1 + LVET/DP) where the K factor was determined using a separate group of individuals undergoing cardiac catheterization. The Pearson correlation between the two methods (dye dilution and above formula) was 0.7744 with a 95% confidence interval of 0.57-0.89 for the true correlation. In 222 SI and 186 usual care (UC) participants with no differences in stroke volume index (SVI) and cardiac output index (CI) at baseline, SVI and CI were systematically lower during the entire period of treatment in SI receiving higher average doses of thiazide diuretics. There was a moderate increase of SVI and CI in SI participants toward baseline after hydrochlorothiazide was replaced by other antihypertensive medication in the fourth year of the trial. We conclude that the lower SVI and CI could have been a contributing factor in the higher mortality in the SI group with ECG abnormalities resulting in decreased coronary flow reserve under stress conditions in these participants with probably pre-existing asymptomatic coronary artery disease.

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 association of liver cirrhosis with arterial essential hypertension has been previously described. The present study extends the previous reports by investigating the hormonal relationships that may occur in patients with established essential hypertension associated to liver cirrhosis. We studied the renin-angiotensin, the adrenergic systems and other vasoactive hormones such as arginine-vasopressin, atrial natriuretic peptide, endothelin and parathyroid hormone in cirrhotic patients with and without essential hypertension. The data suggested that the coincidence of arterial hypertension in cirrhotic patients was characterized by the following findings: a decreased renin-angiotensin activity; a reduced systemic vasodilatation; an increased peripheral pressor effect of vasoactive hormones and an increased effective blood volume.

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 association between hypertension and hyperinsulinemia/insulin resistance is well established but presently unexplained. Among several possible explanations, a connection between the two abnormalities can be envisioned at the level of the microvasculature in skeletal muscle. In fact, the insulin resistance of essential hypertension has been localized in skeletal muscle; in this tissue, on the other hand, rarefaction of the smaller arterioles can generate a rise in blood pressure. Thus, it is theoretically possible that structural changes in small vessels (caused by hypertension) may limit the diffusion of insulin and substrates from the intravascular space to the target cell surface. Alternatively, chronic hyperinsulinemia (caused by primary insulin resistance) could induce changes in small vessel walls (or their reactivity to pressor stimuli) capable of raising blood pressure. The details of these potential mechanisms are laid out within the framework of the hemodynamic phase of in vivo insulin action, and the available evidence bearing on them is discussed.

Previous autoradiographic studies have identified angiotensin II (AII) binding sites over the nodose ganglion and along the vagal afferent neurons. In the present study, we examined whether these binding sites are functional receptors by measuring d.c. potential changes by extracellular recording techniques in the rat isolated nodose ganglion preparation in response to superfusion of angiotensin peptides. It was found that AII, as well as AI and AIII elicited concentration-dependent depolarisation of the nodose ganglion. However, the amino terminal angiotensin heptapeptide, A(1-7), failed to evoke any significant response. The AII receptor antagonist, saralasin had no intrinsic activity, but caused a concentration-dependent blockade of AII-induced depolarisation. This study provides evidence for direct neuronal effects of angiotensin peptides on rat vagal afferent neurons. Moreover, this preparation is a relatively convenient one in which to study functional neuronal AII receptor mechanisms on central or peripheral terminals of vagal sensory neurons.

Cultured aortic fibroblasts from spontaneously hypertensive rats (SHR) exhibit increased proliferation rate compared with cells from normotensive Wistar Kyoto (WKY) rats. The present study was designed to investigate whether this growth abnormality could be accounted for by alteration in protein kinase C (PKC). The enzyme activation by 12-O-tetradecanoyl phorbol 13-acetate (TPA) promoted 3H-thymidine incorporation which was higher in SHR-derived fibroblasts compared with WKY-derived cells. Likewise, 3H-phorbol 12,13-dibutyrate (PDBu) binding to intact cells was markedly increased in SHR-derived fibroblasts. These findings suggest a difference in PKC activity between the two cell types. In both cell types, serum-induced 3H-thymidine incorporation was enhanced by PKC down-regulation, which was obtained by prolonged treatment of cells with high dose of TPA, whereas it was inhibited in a dose-dependent manner by activation of the enzyme. The changes in serum-induced 3H-thymidine incorporation elicited either by activation or desensitization of PKC, did not differ between SHR and WKY fibroblasts. Our results indicate therefore i) that in the presence of serum PKC exerts an antiproliferative effect in rat aortic fibroblasts and ii) that the increase in PKC activity and in sensitivity to TPA exhibited by SHR-derived fibroblasts, is not involved in the increased proliferation rate displayed by SHR-derived fibroblasts in serum-containing medium.

For the first 98.5% of mankind's existence, prehistoric people all ate low-sodium, high-potassium, low-fat diets. With evolutionary forces working all this while, humans became very well adapted to the low-sodium, high-potassium, low-fat diet. In modern times, man has deserted his ancient cuisine and now favours a high-sodium, low-potassium, high-fat diet, which has produced several 'diseases of civilization', including hypertension. Many studies indicate that a 'normal'-potassium diet can prevent many of these arterial and renal lesions, even though the blood pressure remains equally hypertensive. The high-potassium diet also tends to retard the development of hypertension. The use of the high K diet is a prime example of protecting arteries in a hypertensive setting. This is the new dimension in hypertension therapy, protecting the arteries in addition to normalizing the blood pressure.

Randomized controlled trials along with 'within group' studies of patients with symptomatic coronary artery disease suggest that dietary and other lifestyle changes can halt progression of coronary atherosclerosis, induce regression of pre-existing severe lesions, and reduce the severity or frequency of angina. Varying combinations have been tested, including restriction of dietary total, saturated and polyunsaturated fat using lean meat or vegetarian diets, fish oil supplements, smoking cessation, stress management, and exercise training. The relative importance of each of these remains unclear. In patients with recent myocardial infarction high fish diets appeared effective in reducing both ischaemic heart deaths and total death rates over two years, whereas modest changes in dietary saturated fats or fibre had no influence on outcome. These results suggest that a far more active dietary approach is needed for patients with symptomatic coronary disease. Further research is required into the possible complementary role of dietary measures and drug treatment for reversing the disease process and improving outcome, using new techniques for achieving behavioural change.