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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As the major regulator of arterial blood pressure and sodium balance, the renin axis supports normotension or hypertension via angiotensin-mediated vasoconstriction and angiotensin plus aldosterone-induced renal sodium retention. In this endocrine servo control, renal renin is released by hypotension or salt depletion; conversely, with hypertension or volume excess, plasma renin activity falls to zero. Accordingly, any renal renin secretion is abnormal in the face of arterial hypertension. Human hypertensive disorders comprise a spectrum of abnormal vasoconstriction-volume products (renin-sodium profiles). Excess plasma renin activity for the sodium balance is created by nephron heterogeneity in which a subpopulation of ischemic nephrons hypersecretes renin and retains sodium. This excess renin impairs adaptive natriuresis of neighboring normal nephrons. Research defining the pivotal role of vascular cytosolic calcium for transducing sodium or renin-mediated vasoconstriction explains the selective value of calcium antagonists for correcting the sodium-volume-mediated, and beta-blockers or angiotensin converting enzyme inhibitors for correcting renin-mediated, arteriolar vasoconstriction. The renin precursor prorenin appears to be physiologically active, causing selective vasodilation that offsets renin-mediated vasoconstriction. Overactivity of prorenin may be involved in the hyperperfusion vascular injuries of diabetes mellitus and toxemias. Prorenin underactivity may facilitate renin-mediated ischemic vascular injury. In essential hypertension, undue plasma renin activity is powerfully and independently associated with heart attack risk. Conversely, patients with low renin activity are protected from heart attack despite higher blood pressures and greater age. Also, renin or angiotensin administration consistently causes vascular injury in the heart, brain, and kidneys of animals. These data suggest new potentials for the prevention of cardiovascular sequelae (heart attack and stroke) by using explicit strategies to curtail plasma renin activity.
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PMID:Lewis K. Dahl Memorial Lecture. The renin system and four lines fo hypertension research. Nephron heterogeneity, the calcium connection, the prorenin vasodilator limb, and plasma renin and heart attack. 151 45

Blood levels of natriuretic hormones (atrial natriuretic peptide and digitalis-like natriuretic factor) were measured in 93 patients with Stages I and II essential hypertension and 31 healthy individuals. The baseline level of digitalis-like natriuretic factor was higher in the patients with Stage II essential hypertension than in the healthy individuals. This parameter was normal in the patients with Stage I hypertension. The concentration of atrial natriuretic peptide was not greatly different in the patients from that in the healthy persons. Water and salt loads were reported to affect the blood levels of natriuretic hormones. The levels of the hormones were shown to be correlated between them and with blood pressures and the activity of the renin-angiotension-aldosterone system. It was suggested that the natriuretic hormones might play a compensatory role in the pathogenesis of essential hypertension.
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PMID:[Natriuretic hormones (atrial and digitalis-like) in patients with arterial hypertension during exercise]. 153 94

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients.
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PMID:The pharmacokinetics of perindopril in patients with liver cirrhosis. 157 57

Blood pressure in patients with essential hypertension is raised by sodium chloride but not by nonchloride sodium salts. Although a high sodium chloride diet is known to augment the pressor response to norepinephrine and angiotensin II, the effect of nonchloride sodium salts on pressor responsiveness has not been studied so far. To examine whether sodium chloride and nonchloride sodium salts evoke different pressor responses to these agonists, we performed graded norepinephrine and angiotensin II infusions in salt-sensitive (n = 7) and salt-resistant (n = 8) normotensive subjects. The subjects were given a low salt diet (20 mmol/day) for 3 weeks, to which a supplement of 200 mmol sodium per day, provided as either sodium chloride or sodium citrate, or a placebo was added for 1 week each. We found that, although sodium chloride raised mean arterial blood pressure in the salt-sensitive subjects (p less than 0.005), sodium citrate did not. However, under both sodium salts pressor response to norepinephrine and angiotensin II was significantly greater than under placebo (p less than 0.02). Furthermore, with both sodium salts, pressor response in the salt-sensitive subjects was greater than in the salt-resistant subjects (p less than 0.01). This study thus demonstrates that, although blood pressure in salt-sensitive individuals is raised by sodium chloride only, both sodium chloride and sodium citrate evoke similar increases in pressor response to norepinephrine and angiotensin II. Since pressor response increased with both sodium salts but resting blood pressure increased only with sodium chloride, enhanced pressor responsiveness alone cannot account for the sodium chloride-induced rise in resting blood pressure.
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PMID:Effects of sodium salts on pressor reactivity in salt-sensitive men. 159 48

Fractional excretion of lithium (FeLi) is a marker of proximal tubular sodium reabsorption. During different sodium intakes (normal = 120 mEq/day, low = 40 mEq/day and high = 240 mEq/day) fractional lithium excretion was evaluated in essential hypertensive patients (n. 19) and control subjects (n. 5). Our data showed that FeLi was higher in hypertensives than in controls. Dividing hypertensives on the basis of blood-pressure sensitivity, salt resistant patients showed lower FeLi levels as compared to salt sensitive ones. Our findings indicate that proximal tubular sodium reabsorption is decreased in essential hypertension; this behavior is particularly evident in salt sensitive patients, suggesting that factors affecting proximal tubular function are activated in these patients in order to reduce the impairment of renal excretory capability.
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PMID:[Behavior of the lithium excretion fraction in hypertensive patients during variations of sodium intake]. 163 54

Insulin resistance associated with a hyperinsulinemic response to oral glucose intake has been found in patients with essential hypertension and is believed to play a role in inducing hypertension by causing renal sodium and water retention. We therefore examined whether salt-sensitive, young normotensives, assumed to be predisposed to essential hypertension, exhibit impaired glucose tolerance in a similar way. The plasma insulin and glucose response to oral glucose intake (75 g) was assessed in 23 healthy, lean, male volunteers ingesting either 20 mmol or 260 mmol NaCl/day for 6 days each in a single-blind randomized crossover study. Salt sensitivity was defined as a significant drop in mean arterial blood pressure greater than 3 mmHg (means of 30 readings in the supine subject; P less than 0.05) under the low-salt diet. Following the glucose load, plasma levels of both glucose and insulin were significantly higher (P less than 0.01) in the salt-sensitive (n = 10) compared with the salt-resistant subjects (n = 13) during the high-salt diet but not during the low-salt diet. Whereas in the salt-sensitive group glucose tolerance improved with dietary salt restriction (P less than 0.01), it deteriorated in the salt-resistant group (P less than 0.05). Following the glucose load under the high-salt diet, there was a significant drop in blood pressure in the salt-sensitive (P less than 0.005) but not the salt-resistant subjects. The hyperglycemic and hyperinsulinemic response in salt-sensitive subjects suggests that insulin resistance is present in these subjects prior to the development of hypertension and that it can be ameliorated by salt restriction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Salt sensitivity in young normotensive subjects is associated with a hyperinsulinemic response to oral glucose. 164 59

The pathophysiological role of the central dopaminergic mechanism in human essential hypertension (EHT) is still unknown, so we investigated a possible relationship between the central dopaminergic activity and salt sensitivity to blood pressure in patients with EHT. We divided 22 inpatients with EHT into salt-sensitive (SS, n = 11) and non-salt-sensitive (NSS, n = 11) groups according to an 8% increase of mean blood pressure (MBP) when dietary salt intake was increased from 2 g/day to 20 g/day for two periods of 7 days each. The change of central dopaminergic activity by salt load was evaluated as the percentage change of plasma prolactin (PRL) response to a small dose (25 micrograms) of thyrotropin-releasing hormone (TRH) administered intravenously. The mean percentage change of PRL response by salt load in the SS group was -9.4 +/- 8.5% (mean +/- SEM), which was remarkably lower than the 26.8 +/- 5.5% in the NSS group (P less than .01). There was a significant negative correlation between the percentage change of PRL response and that of MBP by salt load (r = -0.456, P less than .05). These results suggest that a lack of activation of the central dopaminergic system by salt load may contribute in part to a rise in blood pressure in SS patients with EHT.
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PMID:Salt sensitivity and central dopaminergic activity in patients with essential hypertension. 168 22

Dopamine, an ancestral catecholamine, is physiologically natriuretic and vasodilating, thus essentially protecting against hypertension. Its actions are overshadowed by the opposite effects of its main biological partner, norepinephrine, and this is accentuated with aging. Clinical observations combined with molecular biology approaches to catecholamine-synthesizing and catecholamine-metabolizing enzymes and receptors permit the identification of some inborn defects. Subtle changes in the dopamine-norepinephrine balance may account for the enhanced peripheral noradrenergic activity seen in the setting of decreased dopaminergic activity in advanced age. These changes may contribute to the diminished ability of the aged kidney to excrete a salt load, as well as to the finding that systolic blood pressure increases with age in populations with a high, but not in those with a low, intake of salt. The attainment of advanced age in Western societies with adverse lifestyle changes (mental rather than physical stress, excess salt intake, overeating, sedentarism) appears to facilitate the development of hypertension. The adaptation to all the preceding lifestyle changes necessitates an increased dopamine generation, which may initially compensate to maintain appropriate natriuresis and vasodilation since many patients with initial borderline essential hypertension express their sympathetic hyperfunction, in addition to increased norepinephrine release, by excessive dopamine release. However, the progression of hypertension is accompanied by a peripheral dopaminergic deficiency and diminished ability to excrete salt. This may represent an eventual inadequacy of a phylogenetically redundant system resulting in decreased natriuresis and vasodilation and may account for the responsiveness of established chronic hypertension to salt restriction, diuretics, and dopaminomimetic medication.
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PMID:Peripheral dopamine in pathophysiology of hypertension. Interaction with aging and lifestyle. 168 57

Acute response in blood pressure (BP) and natriuresis to saline infusion was evaluated in 16 patients with primary aldosteronism caused by aldosteronoma (PA) and 12 patients with salt-sensitive essential hypertension (SSEH). Salt-sensitivity was defined by a decrease in mean BP exceeding 5% at the second hour after a 20 mg furosemide injection. Plasma renin activity (PRA), plasma aldosterone concentration (PAC) and urine electrolytes in response to saline infusion were determined. During a 2-liter isotonic saline infusion, a similar degree of natriuresis and change in BP were observed in PA and SSEH patients. A significantly inverse correlation between the increase in mean BP and the degree of natriuresis at the end of the infusion was found in patients with SSEH (r = -0.80, p less than 0.01). No correlation was observed between these parameters in patients with PA (r = 0.28, p greater than 0.05). These results suggest that hypernatriuresis in SSEH may play a protective mechanism against abrupt increases in BP and volume during acute saline loading. This protective mechanism was not evident in patients with PA.
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PMID:Exaggerated natriuresis in primary aldosteronism. 168 71

This study examines the effect of various plasma proteins from man on the spontaneous contractile activity of the rat portal vein. Albumin, gamma-globulin, alpha-globulin, beta-globulin (the major plasma proteins), and immunoglobulin IgG (the major immunoglobulin present in the gamma-globulin fraction) were obtained commercially. Mesenteric portal vein strips were prepared from rats and placed in a physiological salt solution in muscle baths for the measurement of longitudinal mechanical response. Portal veins exposed to albumin or gamma-globulin showed a dose-dependent increase in the spontaneous activity, whereas those exposed to alpha-globulin or alpha- and beta-globulin together showed a dose-dependent inhibition of spontaneous activity. Immunoglobulin IgG produced a dose-dependent increase in the spontaneous activity similar to that of gamma-globulin. The increased spontaneous activity produced by albumin was not prevented by ouabain but was inhibited by phentolamine. Spontaneous contractile activity was stimulated by albumin in the chemically (6-hydroxydopamine) denervated portal vein. These findings indicate that albumin acts in a manner similar to noradrenaline. The increased spontaneous activity caused by gamma-globulin (IgG) was inhibited by ouabain or verapamil. The effect of IgG was not dependent on alpha-adrenergic, cholinergic, histaminergic, serotoninergic, or renin angiotensin systems nor was it affected by removal of the endothelium. These observations may have implications in the pathophysiology of essential hypertension.
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PMID:Effect of human plasma proteins on spontaneous contractile activity of rat mesenteric portal vein. 169 38


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