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

Alterations in intracellular cation metabolism have been implicated in the pathophysiology of essential hypertension. Total magnesium, calcium, sodium and potassium levels were studied in serum erythrocytes and platelets, from 154 subjects (76 hypertensive and 78 normotensives; 104 blacks and 50 whites). In the combined black and white hypertensive group, platelet sodium and calcium and erythrocyte calcium were elevated and serum potassium, serum magnesium and platelet magnesium decreased. In the black hypertensive patients, platelet sodium and calcium and erythrocyte calcium were increased, whereas serum magnesium, serum potassium, platelet magnesium and erythrocyte magnesium were decreased. In the white hypertensive group, platelet sodium and erythrocyte calcium were raised and platelet magnesium was decreased. In the black hypertensive patients, serum and platelet magnesium and serum calcium were negatively and erythrocyte and platelet calcium positively correlated with mean arterial pressure. In the white hypertensive patients platelet sodium was directly related to mean arterial pressure. These results suggest that intracellular sodium and calcium overload and magnesium depletion may be important in the pathophysiology of hypertension. Magnesium disturbances are more consistent and widespread in black hypertensive patients than in white hypertensive patients.

The immune system has been linked to the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR). Recently interleukin-2 has been reported to inhibit the development of hypertension in the SHR, but no measures of different lymphocyte populations were made. To test the effect of interleukin-2 we repeated the protocol in the report by injecting forty two day old, male SHR and WKY rats, and in addition, analyzed lymphocyte subpopulations. Untreated, age matched rats of the same strain were used as a control. At three and four months of age blood was drawn from all animals. Monoclonal antibodies were used to fluorescently label different lymphocyte subpopulations. The populations examined were the total T-cells, T-nonhelper cells, T-helper cells and B-cells. Total numbers of lymphocytes and white blood cells were also examined. Blood pressures were measured in conscious, restrained animals at two and four months of age. The results showed no attenuation of blood pressure in the interleukin-2 treated SHR at either age. The interleukin-2 treated SHR had a decrease in the percentage of B-cells and an increase in the percentage of T-nonhelper cells relative to the control SHR. Both treated and untreated SHR had increased numbers of white blood cells and lymphocytes compared to both groups of WKY. We conclude that the interleukin-2 used was active but failed to have any effect on blood pressure or absolute numbers of white blood cells and lymphocytes in the treated animals.

We have previously reported that acute volume expansion (VE) with isotonic saline stimulates the production of renal dopamine (DA) which in turn contributes to the accompanying diuresis and natriuresis via activation of renal tubular DA-1 receptors. The purpose of the present study was to determine whether the presence of vagi and/or renal nerves is essential in order to activate the renal dopaminergic system during acute VE. Acute VE (6% body weight) with isotonic saline was performed in two groups of anesthetized rats, one of which served as sham control whereas the other was subjected to bilateral cervical vagotomy. The diuretic and natriuretic responses to acute VE did not differ between the sham control and vagotomized groups. However, urinary DA excretion (UDAV) was significantly increased in the sham control but not vagotomized group. Pretreatment with SCH 23390, a selective DA-1 receptor antagonist led to significant attenuation of the diuretic and natriuretic response to acute VE in the sham control but not vagotomized group. In another group of animals, the diuretic and natriuretic response to acute VE was studied in rats subjected to acute unilateral renal denervation. Basal UDAV was not significantly different between the denervated (DNX) kidney and the contralateral innervated (INX) kidney. Acute VE evoked diuresis and natriuresis in both kidneys, the response in the DNX kidney being significantly greater when compared to that in the INX kidney. UDAV increased significantly and to similar levels in both kidneys. Pretreatment with SCH 23390 led to attenuation of the diuretic and natriuretic response to acute VE in the DNX but not INX kidney. After DA-1 receptor blockade, the residual renal response to volume expansion in the DNX kidney did not differ significantly from that in the INX kidney. The results of this study suggest that 1) afferent vagal pathways appear to mediate the VE induced stimulation of renal DA production; 2) the increase in UDAV during acute VE occurs primarily through a mechanism which is independent of renal noradrenergic and putative dopaminergic nerves.

Recent data suggest that echocardiographic left ventricular (LV) hypertrophy is associated with increased cardiovascular morbidity and mortality. Based upon application of sex-specific echocardiographic criteria for LV hypertrophy, the clinical characteristics of 863 subjects with and 4097 subjects without LV hypertrophy are examined. Subjects with LV hypertrophy are older, more obese, have higher blood pressure, and are more likely to have pre-existing coronary artery disease. In addition subjects with LV hypertrophy have a higher prevalence of reduced echocardiographic fractional shortening. We conclude that subjects with echocardiographic LV hypertrophy are at high risk for cardiovascular disease complications by virtue of their clinical profile. Additional investigation of the benefits of therapeutic interventions directed toward the prevention or regression of LV hypertrophy is warranted.

Under certain circumstances the effect of insulin to promote glucose uptake in peripheral tissues is reduced because of a resistance to insulin action. This insulin resistance and the resulting hyperinsulinaemia are now recognised as common background factors that may be responsible for hypertension, hyperlipidaemia, decreased thrombolysis and also impaired glucose tolerance and diabetes. Hyperinsulinaemia has also been identified as an independent risk factor for coronary heart disease and promotes smooth muscle cell growth and plaque formation. A series of studies have now demonstrated that treatment with selective beta-blockers as well as thiazide diuretics impair insulin sensitivity by 15-30% and causes a compensatory increase in insulin concentrations. Furthermore, lipoprotein concentrations are affected in an unfavourable way. This is in contrast to the drugs belonging to ACE-inhibitors, calcium-channel blockers and alpha 1-blocker classes that are either neutral or may have the opposite effects in these respects.

The relation between the maximal velocity of red blood cell sodium-lithium countertransport and blood pressure/hypertension has been studied in 2,748 men and women aged 25-74 years who participated in the 1983-85 baseline examination of the Gubbio Population Study, an epidemiologic investigation performed in a hill town of north central Italy. Men had a higher sodium-lithium countertransport velocity than women at all ages, and, in both sexes, a higher velocity was observed at successive ages. Hypertensives of both sexes had a higher sodium-lithium countertransport velocity than normotensive individuals, the difference remaining significant after control for age, body mass index and plasma uric acid concentration. Individuals with high sodium-lithium countertransport velocity had significantly greater prevalence of hypertension in both sexes. The data show the existence of a cross-sectional association between sodium-lithium countertransport velocity and hypertension in general population. Prospective study of the Gubbio population is now in progress to investigate the relation between baseline sodium-lithium countertransport velocity, its change over the years and the incidence of hypertension.

The relationship of body fat distribution with blood pressure, fat cell weight and extracellular fluid volume was studied and compared in 20 obese hypertensive men and 20 obese hypertensive women of similar age, degree of overweight and blood pressure level. Body fat distribution, as reflected by the ratio between waist and hip circumference (W/H ratio), was significantly higher in male than in female obese patients. The W/H ratio was positively and independently correlated with systolic arterial pressure both in males and females. However, for the same W/H ratio, systolic arterial pressure was higher in females. The W/H ratio was positively correlated with gluteal fat cell weight only in males and not in females. Both in males and females, the W/H ratio was positively correlated with extracellular fluid volume, independently of the level of blood pressure level and/or the degree of obesity. The study provided evidence that the relationship between body weight and blood pressure in obese hypertensives is affected by the sex-dependence of body fat distribution with possible interferences on fat cell weight and extracellular fluid volume. Several epidemiological studies have emphasized the positive correlation observed between body weight and blood pressure in many. Many investigations have documented the association of blood pressure with body weight, weight to height, overweight or other indices of fatness such as skinfold thickness. However, the correlation coefficients of these different relationships were found constantly small, indicating that the relationship between overweight and blood pressure is somewhat complex. In patients with hypertension, body weight was shown to be strongly related with the levels of both blood pressure and extracellular fluid volume. On the other hand, patients with overweight and hypertension were found to be principally affected by hypertrophic obesity, as shown by the evaluation of fat cell weight. However these findings were exclusively observed in males. No solid data were reported in females. The relationships between body weight and extracellular fluid on one hand, and between body weight and fat cell weight on the other hand, are certainly different in males and in females. First, in females, extracellular fluid volume is submitted to cyclic changes in sodium balance involving the effect of sex steroid hormones. Second, body fat distribution, a parameter which is weakly correlated to blood pressure, is different in males and females. In males, body fat predominates in the upper part of the body while, in females, adiposity is mainly observed in the lower part of the body.(ABSTRACT TRUNCATED AT 400 WORDS)

Our previous studies indicate that dopamine (DA) plays an important role in regulating renal sodium (Na+) metabolism during high Na+ intake, and that DA1 receptors are involved in natriuretic response to acute volume expansion. It has also been shown that in addition to the changes in renal hemodynamics, the natriuretic response produced by exogenously administered DA and DA1 receptor agonists appears to be due to alterations in renal tubular sodium transport mechanisms. This study was designed to investigate the DA1 receptor-mediated changes in Na(+)-H+ antiport activity in tubular brush border membranes of rat kidney. The Na(+)-H+ antiport activity, measured as the amiloride-sensitive Na+ influx in BBMV, was inhibited by 37%, 46%, 33%, and 42% by 1 microM DA, SKF 82958, SKF 38393, and fenoldopam respectively. The DA1 antagonist SCH 23390 increased the antiport activity when given alone, while when administered with an agonist it attenuated the effects of the agonist on the antiporter. DA2 agonists and antagonists failed to affect the antiport activity. These results indicate that the inhibitory effects of DA and DA receptor agonists on Na(+)-H+ antiport activity in renal cortical BBMV were mediated by the DA1 receptors.

To clarify the cardiovascular effects of central vasopressin (AVP), a chronic intracerebroventricular (ICV) infusion of AVP was performed in conscious Wistar normotensive rats. Animals were divided into 3 groups: 1) AVP 1 ng/hr (Low), 2) AVP 100 ng/hr (High), and 3) saline (control) ICV infusion. After a 6 day control period, AVP or saline was continuously infused into the lateral cerebroventricle at a rate of 1 microliter/hr using osmotic minipump for 7 days. As a result, a dose-related elevation of AVP concentration in CSF was achieved. Systolic blood pressure in both Low and High AVP infusion was slightly (7-12 mmHg) but significantly higher than that in control. ICV infusion of AVP did not alter urine volume, electrolytes excretion or osmolality, and AVP vascular antagonist injected intravenously failed to affect mean arterial pressure. Furthermore, plasma catecholamines and renin activity did not differ significantly among the groups. Thus, chronic ICV infusion of AVP induced the elevation of blood pressure, which is due to centrally mediated effect of AVP.

The postulate of a natriuretic factor inhibiting the sodium pump in the kidney led to the detection of increased concentrations of endogenous digitalis-like factors in blood after salt loading, in essential hypertension, in pregnancy-induced hypertension and in chronic hypervolaemia. The recent isolation of ouabain or a close isomer thereof from human plasma and the demonstration of a compound similar if not identical to digoxin in adrenals and human urine shows that mammals like non-vertebrates and toads may synthesize cardiac glycosides in their adrenals and possibly in hypothalamus. The hypothalamus also forms other compounds of unknown structure which bind to the cardiac glycoside receptor site. The differential functions of endogenously formed ouabain and of a digoxin-like substance are unclear. The detailed knowledge of the physiological role of both endogenously formed cardiac glycosides in the regulation of blood pressure has still to be worked out.