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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent research a new series of specific drugs, one of which is guanabenz (GBZ, 2,6(dichlorobenzyliden)-aminoguanidine) has been introduced into the clinical treatment of centrally mediated hypertension. Guanabenz (GBZ) is considered to be among the most specific alpha 2-adrenergic agonists, acting similarly to clonidine by decreasing the sympathetic outflow from the brain to the peripheral circulatory system. In the present report we show that GBZ displays a significant affinity for beta-adrenoceptors. In displacement studies of the iodinated beta-antagonist [125I]cyanopindolol (CYP) from turkey erythrocyte membranes, the dissociation constant of GBZ was 3.8 microM. Inhibition of the (-) epinephrine induced adenylate cyclase activity by GBZ is competitive, with an apparent dissociation constant of 30 microM. A similar value was obtained by studies of GBZ's effect on the (-) epinephrine-induced [3H]cAMP accumulation in intact turkey erythrocytes. In view of its unexpected affinity for beta-adrenoceptors, we examined the three-dimensional structure of crystalline GBZ. In these studies substantial differences between clonidine and GBZ were observed, despite their strong structural resemblance. These dissimilarities (angle of rotation phi = 39.7 degrees as compared to 76 degrees in clonidine, and the rotational restriction of clonidine as compared to the greater mobility in rotation of GBZ) could explain the difference of specificity between these two compounds.
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PMID:Beta-adrenergic activity and conformation of the antihypertensive specific alpha 2-agonist drug, guanabenz. 285 65

We have found increased renal alpha 2-adrenoceptor density and a defect in prostaglandin and parathyroid stimulated adenylate cyclase in two genetic forms of rat hypertension. Changes in serum calcium and parathyroid hormone (PTH) levels suggest biologic significance to this defective adenylate cyclase response. Our hypothesis is that one or more of these defects contribute to excess renal retention of sodium and increase vascular resistance of genetically hypertensive rats and humans with essential hypertension who have similar abnormalities of calcium and PTH.
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PMID:The role of renal catecholamines in hypertension. 298 54

The search for natriuretic hormones or factors by studies of negative pressure breathing, atrial distension experiments, head-out water immersion, expansion of blood volume, Na+/K+-ATPase inhibitors and parabiosis experiments in Dahl rats has led to the finding that the atria are a peptide-secreting endocrine gland. This new natriuretic hormone has now been purified, sequenced and synthetized, and its cDNA and gene have been cloned. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex, and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure, and expansion of blood volume are beginning to emerge.
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PMID:The heart and the atrial natriuretic factor. 298 29

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

Experiments were performed in male Wistar rats with renovascular hypertension (167 +/- 4.2 mmHg) produced by clipping the renal artery for a 3-wk period (2-kidney, 1-clip Goldblatt). The results were compared with those obtained in age-matched normotensive controls. Hypertension of 3-wk duration elicited a significant increase in ventricular weight (1.01 +/- 0.02 g) with respect to the controls (0.82 +/- 0.01 g) but had no significant effect on body weight. The inotropic responsiveness to beta-adrenergic stimulation was diminished in papillary muscles from renal hypertensive rats: the maximum increase in the maximal rate of rise of tension produced by isoproterenol was 27.39 +/- 5.4 and 11.77 +/- 2.91 g X mm-2 X s-1 (P less than 0.05) in control and hypertensive animals, respectively. Similar results were obtained when the estimated maximal velocity of shortening of the contractile element (Vmax) was used to assess myocardial contractility. The inotropic response to CaCl2 was also significantly depressed in the 2-kidney, 1-clip rats. However, the relaxant and the chronotropic responses to isoproterenol were not significantly modified in the Goldblatt rats. Assays of beta-adrenergic receptors to l-[3H]dihydroalprenolol binding, showed no significant changes in the number (expressed per mg of membrane protein) or in the affinity of the beta-receptors. These results suggest that at an early stage of the renal hypertensive model the impaired inotropic response to isoproterenol is not mediated by an alteration of the beta-receptors and should be searched at a postreceptor adenyl cyclase level.
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PMID:Renal hypertension impairs inotropic isoproterenol effect without beta-receptor changes. 299 71

The increased frequency of hypertension in diabetes and of abnormalities of carbohydrate metabolism in hypertension are now well established. It is conceivable that the high coincidence of the two diseases is based on a common metabolic defect. Studies of platelets permit the evaluation of the stimulatory, phosphoinositol-linked and the inhibitory, cyclic adenosine 3',5'-monophosphate-dependent pathways of cell activation. Furthermore, platelets may be relevant for the development of angiopathy through their contents of growth factors. Abnormalities of platelet aggregation have been demonstrated in hypertension and diabetes. They are accompanied by exaggerated stimulation of adenylate cyclase in hypertension and abnormal activity of cyclic guanosine 3',5'-monophosphate phosphodiesterase in diabetes. Defective function of platelets is also observed in patients and animals when the two diseases are present at the same time. Both increased and decreased aggregation have been described in these two diseases in the literature. The apparent discrepancies may be due to different types of platelet preparation, evaluation of aggregation, evolution of defect with age, and form of the disease. Integrated studies of biochemical mechanisms responsible for cell activation are needed to characterize the exact defect present in diabetes and hypertension in platelets.
Hypertension
PMID:Abnormalities of platelet function in hypertension and diabetes. 300 Sep 39

Angiotensin converting enzyme (ACE) inhibitors are not known to have a direct effect on the myocardium. However, there is some evidence to suggest that they can play an important role in protecting the heart during the evolution of hypertensive and coronary arterial disease, both acutely and on a long term basis. Reduction of afterload by balanced arterial and venular dilatation has led to a sustained improvement of cardiac performance both in hypertension and heart failure. Reversal of cardiac hypertrophy has been shown to restore inotropic responsiveness to stimulators of the adenylate cyclase system. Following myocardial infarction, captopril has prevented undue ventricular dilatation and normalized left ventricular chamber stiffness; this prevented deterioration of cardiac function and improved long term survival after infarction. Control of secondary aldosteronism and prevention of hypokalaemia can play an important role in the prevention of cardiac arrhythmias. The lack of reflex sympathetic stimulation during long term captopril therapy can also play a favourable role in that respect. Although highly speculative, evidence is accumulating that ACE inhibition could have a cardioprotective effect in acute myocardial ischaemia. It is based on the demonstration that renin can be produced by myocardial cells, that angiotensin is liberated by the ischemic myocardium and that angiotensin in high renin conditions plays an active constrictor role in regulating the coronary circulation.
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PMID:Prospectives for angiotensin converting enzyme inhibition in heart diseases. 300 6

Platelets provide an accessible and homogeneous cellular system for investigative studies on hypertension. Hypertension-associated abnormalities of cyclic adenosine 3',5'-monophosphate (AMP) metabolism were studied in human platelets. Platelets from hypertensive subjects had an enhanced cyclic AMP accumulation response to prostaglandin E1 (twofold increase in prostaglandin E1 sensitivity). The degree of adenylate cyclase activation in response to both prostaglandin E1 (receptor-mediated) and forskolin (non-receptor-mediated) was greater in hypertensive than normotensive subjects, and prostaglandin E1-stimulated and forskolin-stimulated adenylate cyclase activity correlated directly (r = 0.71, p less than 0.001, n = 26). This finding suggests that the catalytic subunit of the enzyme is the rate-limiting step of this hormonal information transduction. Platelets from hypertensive subjects were more sensitive to epinephrine-induced inhibition of the stimulatory effects of prostaglandin E1 on both cyclic AMP accumulation (fourfold) and activation of cyclic AMP-dependent protein kinase. These findings suggest that the enhanced cyclic AMP metabolic response to prostaglandin E1 in platelets from subjects with established essential hypertension may function as a negative feedback mechanism to protect the cells against calcium overload and to reduce their stimulated participation in hemostatic and thrombotic processes.
Hypertension 1986 Aug
PMID:Enhanced platelet cyclic AMP response to prostaglandin E1 in essential hypertension. 301 95

Two independent series of biomedical investigations have led to the discovery that the atria are a peptide-secreting endocrine gland. The first is mainly morphological and starts with the finding that mammalian atrial but not ventricular cardiocytes contain "dense bodies". These "dense bodies" later called "specific granules" were found to be different from lysosomes, to be made up of proteins and to incorporate both 3H-leucine and 3-H-fucose in a pattern typical of peptide-secreting endocrine cells. The finding that rat atrial granulation varied with the sodium and water balance led to the crucial observation that atrial extracts have natriuretic and diuretic effects. In less than 4 years, this new natriuretic hormone has been purified, sequenced and synthetized, and its cDNA and gene have been cloned. The ANF gene has been assigned to the distal short arm of chromosome 1 in band 1P36 while the mouse gene is localized in chromosome 4. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure and expansion of blood volume are already beginning to emerge. On the other hand, the search for natriuretic hormones or factors by studies of negative pressure breathing, atrial distention experiments, head-out water immersion, expansion of blood volume, Na+/K-ATPase inhibition and parabiosis experiments in Dahl rats has provided a general framework within which to interpret this new cardiac function.
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PMID:[The heart, an endocrine gland]. 301 75

To determine the role of dietary sodium intake in the reduction in beta-adrenergic sensitivity in hypertension, lymphocyte beta-receptors from 8 borderline hypertensive and 16 normotensive subjects were studied after 5 d on a high sodium diet (400 meq/d) and also following a low sodium diet (10 meq/d). During the high sodium diet, lymphocyte beta-receptor-stimulated adenylate cyclase activity, expressed as the relative increase over basal levels stimulated by the beta-agonist isoproterenol, was significantly (P less than 0.025) decreased in hypertensive (24 +/- 5%, mean +/- SE) compared with normotensive (42 +/- 4%) subjects. Neither beta-receptor density nor the proportion of nonsequestered beta-receptors differed between groups. A low sodium diet significantly increased beta-receptor-stimulated adenylate cyclase activity in hypertensives (low sodium, 51 +/- 7%; high sodium, 24 +/- 5%, P less than 0.025) to a level not different than that of normotensives (46 +/- 5%). Thus, reduced lymphocyte beta-receptor responsiveness in hypertensive subjects is not due to beta-receptor sequestration and is corrected on a low sodium diet. Dietary sodium may be an important factor in the beta-receptor defect in early hypertension.
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PMID:Low sodium diet corrects the defect in lymphocyte beta-adrenergic responsiveness in hypertensive subjects. 302 62


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