Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pattern of cardiac beta-adrenergic receptor changes in different hypertrophy models varies according to the pathophysiology. In salt-sensitive Dahl rats, high dietary salt intake leads to a moderate degree of cardiac hypertrophy associated with increased numbers of cardiac beta-adrenergic receptors but unchanged affinity for agonists. Isoproterenol-stimulated cardiac adenylate cyclase is also higher in salt-loaded hypertensive rats without any change in basal or NaF-stimulated activities. In contrast, neither beta-adrenergic receptors nor adenylate cyclase activities are affected by variations in dietary salt in salt-resistant Dahl rats. The extent of isoproterenol-induced down regulation of beta-adrenergic receptors on isolated cardiac myocytes as well as the recovery from this down regulation is not significantly different in either strain of Dahl rats and is not influenced by dietary salt. The enhancement of beta-adrenergic pathways in salt-dependent genetic hypertension may be involved both in the initiation of cardiac hypertrophy and the preservation of contractile function.
Hypertension
PMID:Cardiac beta-adrenergic receptors in salt-dependent genetic hypertension. 299 64

Blood vessel responses to relaxant drugs have been reported to change with aging and with the development of hypertension. In view of the requirement of endothelial cells for the activity of many relaxant drugs, we examined the role of the endothelium in the relaxation response of vascular tissue. Aortic and mesenteric ring segments from normotensive and hypertensive rats, ages 5 to 6, 15 to 18 and 30 to 31 weeks, were examined for relaxation to sodium nitroprusside, sodium nitrite, atrial natriuretic factor and 8-bromo-cyclic GMP. Relaxation responses to the nitrovasodilators were reduced progressively with aging in ring segments of Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) with intact endothelium; however, intact SHR ring preparations displayed less relaxation to nitrovasodilators at 15 to 18 and 30 to 31 weeks than those of WKYs. Rubbed (endothelium denuded) ring preparations displayed greatest relaxation to nitrovasodilators with no difference being observed between SHR and WKY preparations at any age tested. Relaxation to atrial natriuretic factor and 8-bromo-cyclic GMP was not different between rubbed and unrubbed ring segments or between SHRs and WKYs, indicating no detectable impairment of the overall relaxation response in the vascular smooth muscle of SHRs. These results suggest that the total functional capacity of vascular smooth muscle to relax to nitrovasodilators is not changed with aging or hypertension. However, the endothelial cells exert modulatory influences upon the vascular smooth muscle to reduce overall responsiveness to nitrovasodilators, an effect that is enhanced with aging and the development of genetic hypertension.
 ...
PMID:Endothelial modulation of vascular relaxation to nitrovasodilators in aging and hypertension. 302 22

The sodium-proton exchange activity was determined in lymphocytes of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and domestic Wistar rats. Uptake of sodium was determined by measuring the osmotic swelling of lymphocytes after activation of the exchanger by suspension of the cells in sodium propionate and consequent intracellular acidification by the permeant weak acid. Fractional swelling (mean +/- SEM) in 16 SHR and 16 WKY was 0.44 +/- 0.03 and 0.35 +/- 0.02, respectively (p less than 0.01). The swelling was partially inhibitable by amiloride and, at 10(-4) M concentration, the amiloride-sensitive swelling was 0.21 +/- 0.02 in SHR and 0.11 +/- 0.01 in WKY (p = 0.001). Progressive extracellular ion substitutions of chloride for propionate or of potassium for sodium showed that the exchange activity was related linearly to cellular acidification; however, the dependence on extracellular sodium displayed saturation characteristics, with the same apparent Km for cells from SHR and WKY and a Vmax of 0.54 +/- 0.03 for SHR and 0.39 +/- 0.02 for WKY (p less than 0.002). External lithium could replace sodium on the exchanger but abolished the differences between strains. Results in the domestic Wistar rats were similar to those of WKY. These results suggest that lymphocytes of the SHR have a greater capacity for sodium uptake through the sodium-proton exchanger, as compared with normotensive strains. If shared by other cells, such an increased capacity could have a pathophysiological role in genetic hypertension. In particular, its presence in proximal renal tubular cells would support the hypothesis of a primary role for the kidney in the pathogenesis of genetic hypertension.
Hypertension 1987 Mar
PMID:Lymphocyte membrane sodium-proton exchange in spontaneously hypertensive rats. 302 56

Considerable controversy exists concerning the possible role of lead in the etiology of human hypertension. In animal studies, there is convincing evidence that lead alters cardiovascular responsiveness; rats drinking water containing 100 ppm lead develop a chronic, significant 15 to 20 mm Hg elevation in systolic blood pressure. Pressor responsiveness to catecholamines is enhanced in animals chronically exposed to lead, and the responsiveness of isolated vascular smooth muscle to adrenergic agonists is increased in rats with lead-induced hypertension. Experimental evidence suggests that alterations in the cellular mechanisms that regulate intracellular calcium concentration may contribute to the abnormal vascular function in lead-induced hypertension. Recent work in our laboratory indicates that increased vascular reactivity in genetic hypertension is associated with altered activity of the protein kinase C branch of the calcium messenger system. Contractile responses to lead in rabbit mesenteric artery are potentiated by activators (phorbol esters) of this enzyme complex, and a selective inhibitor of protein kinase C inhibited contractions induced by lead. Based on these results, it is proposed that a cellular component of the action of lead to increase vascular reactivity may relate to the role of protein kinase C in smooth muscle contraction.
 ...
PMID:Effects of lead on vascular reactivity. 306 Mar 55

Despite renal involvement in the genesis of hypertension, the precise renal hemodynamic events prior to and during development of hypertension have not been obtainable by direct study in the available rat models of genetic hypertension. We have developed a model of genetic salt-sensitive hypertension in rats with superficial glomeruli, using the protocol described by Dahl to develop the Brookhaven model. Adult Munich Wistar rats were purchased from Charles River and bred in our laboratory. Offspring were allowed to mature without intervention. Systolic blood pressure and body weight were measured weekly to determine the normal longitudinal changes with increasing age for this strain. Balance studies were also carried out longitudinally, and during these studies plasma renin activity (PRA) was determined. When the rats were 16 weeks old, the availability of superficial glomeruli was assessed under microscopic examination and only those rats with numerous superficial glomeruli/field were mated. The offspring of these breeders were used as the zero generation (F0) of salt-sensitive rats, and were treated as described by Dahl. Systolic blood pressure, body weights and balance studies were carried out in this and in all subsequent generations. Sibling breeding was maintained and rats were bred for salt-sensitivity (systolic blood pressure greater than 155 mmHg at the age of 2 months) and availability of superficial glomeruli. Those rats with systolic blood pressure of less than 120 mmHg were bred in an attempt to develop a salt-resistant strain, and untreated Munich Wistar rats were bred to provide another control.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A new model of genetic hypertension in rats with superficial glomeruli. 307 78

In order to assess the pathophysiological role of the renal Thromboxane (Tx)A2 in genetic hypertension, the urinary excretion of its stable metabolite: the TxB2 was followed in groups of 12 hypertensive (LH), normotensive (LN) and low blood pressure (LL) female rats of the Lyon strains at the ages of 5, 9, 21 and 32 weeks. In the 3 strains studied, the urinary TxB2 excretion markedly decreased between 5 and 9 weeks of age and did change thereafter. In addition, 5 and 9 weeks old rats exhibited an increased urinary TxB2 output compared to LN and LL controls. Since TxA2 is a potent vasoconstrictor, it seems likely to hypothesize that the early increase observed in the renal TxA2 biosynthesis could be one of the primary events occurring during the development of hypertension in this rat model.
 ...
PMID:[Urinary excretion of thromboxane B2 in the genetically hypertensive rat of the Lyons strain]. 309 2

Recent studies in essential hypertensive patients and rats with genetic hypertension strongly suggested that the development of primary hypertension results from a transient and chronic "cascade" of events; I) excess Na+ intake, II) secretion of natriuretic factors, III) abnormal cell Na+ homeostasis in the vascular wall, due to the presence of inherited and induced abnormalities in different Na+ transport system and IV) increase in cytosolic free Ca2+ content and sympathetic drive. In vitro studies have previously shown that canrenone, an antihypertensive antialdosterone drug, behaves like a partial agonist at the digitalis-receptor site of the Na+, K+-pump. In particular, it has been shown that canrenone counterbalances the increases in internal Na+ and cytosolic free Ca2+ contents induced by ouabain in cultured smooth muscle cells. We thus investigated the effect of canrenone administration in a model of experimental hypertension with increased endogenous "ouabain-like" factors (rats with reduced renal mass under excess Na+ intake: RRM-salt rats). Results presented here confirm that RRM-salt rats exhibit: volume expansion, strongly decreased plasma renin activity, increased endogenous "ouabain-like" factors and (IV) decreased Na+, K+-pump activity and increased Na+ content in erythrocytes. In addition, we found that canrenone is antihypertensive in this model and this is associated with a tendency to normalize volume expansion, plasma levels of endogenous "ouabain-like" factors, Na+, K+-pump activity and Na+ content in erythrocytes. In conclusion, our results suggest that administration of canrenone to RRM-salt rats may induce a lowering of blood pressure by antagonism with endogenous "ouabain-like" factors at the vascular wall.
 ...
PMID:[Canrenone: an effective antihypertensive in an experimental model of hypertension in which the active transport of sodium is diminished]. 309 4

The systemic and renal hemodynamic effects of diltiazem were determined in patients with mild to moderately severe essential hypertension and in rats with spontaneous hypertension (SHR). Seven patients were treated for one full year (300 mg/day, average dose) and 10 SHR and 10 normotensive Wistar-Kyoto (WKY) rats received 1 and 2 mg/kg, intravenously. In both man and rat with genetic hypertension, arterial pressure was reduced through a fall in total peripheral resistance without associated reflexive increases in heart rate and cardiac index; and the patients demonstrated no change in plasma volume. In both man and the SHR: renal blood flow increased (in SHR not statistically significant) as arterial pressure and renal vascular resistance fell; glomerular filtration rate (GFR) remained unchanged and the filtration fraction (FF) significantly fell; and calculated intrarenal hemodynamic indices (using the Gomez formulae) demonstrated falls in afferent and efferent glomerular arteriolar pressures and resistances and in intraglomerular pressures, thereby explaining the unchanged GFRs and the decline in FF. These findings in both hypertensive man and rat are in contrast with those of the normotensive WKY that only demonstrated a fall in afferent glomerular arteriolar resistance. Thus, these data demonstrate that diltiazem controlled arterial pressure in both forms of genetic hypertension associated with falls in systemic and renal arteriolar resistances and with improved intrarenal hemodynamics without glomerular hyperfiltration.
 ...
PMID:Diltiazem maintains renal vasodilation without hyperfiltration in hypertension: studies in essential hypertension man and the spontaneously hypertensive rat. 315 72

Dysfunction of ion handling, including binding and fluxes (passive and active transport) of physiologically important ions such as potassium, sodium, calcium, and magnesium, by vascular smooth muscle cell membranes has repeatedly been reported to be associated with the pathophysiology of hypertension. The specific purpose of this review is to summarize and evaluate the evidence for alterations of calcium ion (Ca2+) handling by vascular smooth muscle in various forms of hypertension in the animal model on the basis that regulation of cytoplasmic Ca2+ concentration is a complex and yet vitally important process for a normal function of vascular smooth muscle and that derangement of such a regulation may result in excessive retention of cytoplasmic Ca2+, contribute toward increase of total peripheral resistance, and ultimately lead to elevation of blood pressure. Emphasis is placed upon the consideration of the usefulness of the subcellular membrane fractionation technique in studies of binding and transport of Ca2+ by vascular and nonvascular smooth muscle membranes from genetic as well as experimental hypertensive rats. The limitations of the interpretation of data using such an approach are also considered. Decreased active transport of Ca2+ across isolated plasma membrane vesicles from large and small arteries occurs in several but not all forms of hypertension. This membrane abnormality also occurs in nonvascular smooth muscles and other tissues or cells not confined to the cardiovascular system in genetic hypertension, but not in experimental hypertension. A hypothesis of general membrane defects in spontaneous hypertension is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Dysfunction of calcium handling by smooth muscle in hypertension. 315 69

Moxonidine (4-chloro-N-(4, 5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-methyl-5-pyrimidinamine, BDF 5895) reduces blood pressure and heart rate in rats with genetic hypertension (SHR/Okamoto) and in rats with renovascular hypertension (Goldblatt 1 k/1 c). The hypotensive action was also confirmed in renal-hypertensive dogs. The hypotensive action is preceded by a reduction in plasma noradrenaline concentration, thus reflecting a reduction in sympathetic activity. In anesthetized cats, administration of moxonidine into the vertebral artery induces a greater hypotensive effect than i.v. injection of same doses, indicating the central nervous system as the site of hypotensive action. Similar to clonidine, the hypotensive action of moxonidine is abolished by pretreatment of the animals with a selective alpha 2-antagonist. Direct application of moxonidine into the cisterna magna of anesthetized rabbits revealed a 10-fold greater hypotensive potency than clonidine, in contrast to i.v. application where moxonidine was 10-fold less potent than clonidine. At least 10-fold higher doses of moxonidine were needed to cause side effects (sedation, inhibition of gastric secretion), when compared with clonidine. Interruption of presynaptic noradrenergic pathways completely abolished the hypotensive action of moxonidine. Thus moxonidine is endowed with a specific central site of action, presumably by stimulating central presynaptic alpha 2-adrenoceptors. This specific central hypotensive action enables a greater dissociation between the antihypertensive effect on the one hand, and the side effects on the other.
 ...
PMID:General pharmacology of the novel centrally acting antihypertensive agent moxonidine. 319 83


<< Previous 1 2 3 4 5 6 7 8 9 10