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

High calcium diet induces an hypertension lasting one week in normal rats. In mineralocorticoid treated rats (DOCA + NaCl), the same diet prevents for 10 weeks the increase of arterial blood pressure. Parathyroid activity (estimated by urinary cAMP) is decreased after the high calcium diet. These results confirm the role of the parathyroid glands in mineralocorticoid hypertension in the rat.
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PMID:[Arterial blood pressure and high calcium diet in normal and mineralcorticoid (DOCA and sodium chloride hypertensive rats]. 22 48

The concentrations of plasma cAMP and plasma renin activity were determined in arterial and renal venous plasma in nineteen patients investigated for renin-mediated hypertension. The cAMP measurements were performed in two different situations (1) under basal conditions and (2) after i.v. dihydralazine administration, a potent renin stimulation procedure. Thirteen patients had a lateralization of the renin secretion in the basal state and the administration of dihydralazine caused a further marked renin-secretion. The cAMP concentration was higher in the renal veins draining renin-positive kidneys than in the contralateral renal veins. No significant change was observed between the arterial cAMP concentration and the cAMP concentration in either of the renal veins during dihydralazine-stimulated renin secretion. There was no correlation between the cAMP extraction and the renin secretion of the individual kidneys, but the cAMP extraction correlated with the extraction ratio of PAH. These results show that cAMP values are mainly influenced by the renal function and are not related to the state of renin secretion. Increased cAMP levels in renovascular patients and urameic patients are therefore mainly due to defective elimination of the nucleotide by the kidneys.
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PMID:Cyclic AMP, renal function and dihydralazine-stimulated renin secretion in hypertensive patients. 23 May 70

Changes in cyclic nucleotide metabolism similar to those characteristic of the chronic forms of hypertension were observed in an acute neurogenic form of hypertension in rats produced by electrolytic lesions of the nucleus tractus solitarii. These changes that were evident 2 hr after the lesions were made included decreased cyclic AMP levels in the heart, increased cGMP:cAMP ratio, cAMP phosphodiesterase (3':5'-cAMP 5'-nucleotidohydrolase, EC 3.1.4.17) and guanylyl cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) activities in the aorta and decreased snesitivity of adenylyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) in both the aorta and heart to stimulation by the beta-adrenergic stimulant isoproterenol. These changes appear to depend on catecholamine release and are not due to mechanical distortion secondary to the increased arterial pressure. These studies provide biochemical support to the concept that the sympathetic nervous system may play a critical role in the initiation of the hypertensive syndrome and that chronic hypertension could result from the fixation of the biochemical effects of increased sympathetic activity.
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PMID:Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension. 23 70

The 130 kDa atrial natriuretic factor receptor (ANF-R1) purified from bovine adrenal zona glomerulosa is phosphorylated in vitro by serine/threonine protein kinases such as cAMP-, cGMP-dependent and protein kinase C. This phosphorylation is independent of the presence of ANF (99-126) and there is no detectable intrinsic kinase activity associated with the ANF-R1 receptor or with its activated form. In bovine adrenal zona glomerulosa cells, TPA (phorbol ester) induces a marked inhibition of the ANF-stimulated cGMP accumulation as well as of the membrane ANF-sensitive guanylate cyclase catalytic activity without any change in the binding capacity or affinity for 125I-ANF. However, we have demonstrated a significant 32P incorporation in the ANF-R1 receptor of the TPA-treated cells. The effect of TPA on the zona glomerulosa ANF-R1 receptors was abolished by calphostin C, a specific protein kinase C inhibitor. Altered ANF actions due to blunted response of guanylate cyclase to ANF could be a consequence of the ANF receptor phosphorylation by excessive activity of protein kinase C and might be involved in the pathogenesis of hypertension.
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PMID:Phosphorylation of atrial natriuretic factor R1 receptor by serine/threonine protein kinases: evidences for receptor regulation. 128 Mar 21

Low doses of apomorphine (20-50 micrograms/kg) induced an increase in the activity of an endogenous inhibitor of cAMP dependent protein Kinases (type I inhibitor) in the striatum, anterior and posterior hypothalamus of normotensive rats by stimulating D2-dopamine receptors. In contrast, high doses of the compound (2-10 mg/kg) produced a dose dependent decrease in type I inhibitor activity. In the posterior hypothalamus of vasopressin hypertensive rats and SHR the maximal increase of type I inhibitor activity was markedly higher than in normotensive animals. Moreover, apomorphine induced the increase of type I inhibitor activity in a much wider range of doses. Only as high dose of the compound as 10 mg/kg was able to decrease type I inhibitor activity. This points to a marked supersensitivity of D2 receptors and suggests the subsensitivity of D1 receptors in this brain area of hypertensive rats. In contrast, in the striatum and anterior hypothalamus of hypertensive rats the apomorphine dose response curves were similar to those in normotensive rats. Thus, it seems tha hypertension is associated with the alteration in sensitivity of D2 and D1 receptors in the posterior hypothalamus, the brain area involved in regulation of blood pressure.
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PMID:The responsiveness of D1- and D2-dopamine receptors in the striatum and hypothalamus of spontaneous and vasopressin hypertensive rats. 128 99

Angiotensin II (Ang II) inhibits renin secretion and production from the kidney, but the effect of Ang II on adrenal renin is not clear. Nephrectomy, via elevated plasma adrenocorticotropic hormone (ACTH) and potassium, is a strong stimulator of adrenal renin production in the rat. This stimulation is inhibited by the infusion of Ang II, suggesting a negative feedback between Ang II and adrenal renin. In the present study, we examined the effect of Ang II on adrenal renin using a primary culture of rat glomerulosa cells. Cells were exposed to ACTH (10(-11) M), high potassium (8 and 12 mM), db-cyclic AMP (db-cAMP), (10(-3) M), or Ang II (10(-11) to 10(-5) M) for 24 hours, and active renin and inactive renin were measured. Active renin was predominant in the cells, whereas inactive renin predominated in the medium. Ang II stimulated renin production in a dose-dependent fashion (cell-active renin, 1.21 +/- 0.20 to 2.39 +/- 0.16; medium-inactive renin, 2.59 +/- 0.40 to 6.14 +/- 0.49 ng Ang I/10(6) cells). Both ACTH and db-cAMP significantly stimulated active renin in the cells (ACTH, 1.73 +/- 0.14 to 9.44 +/- 0.98; db-cAMP, 1.45 +/- 0.16 to 3.96 +/- 0.71 ng Ang I/10(6) cells) and inactive renin in the medium (ACTH, 4.98 +/- 0.38 to 43.7 +/- 5.63; db-cAMP, 3.80 +/- 0.32 to 33.55 +/- 5.62 ng Ang I/10(6) cells). The addition of Ang II (10(-7) M) blunted the stimulation of renin production by both ACTH and db-cAMP by 60%. High potassium-stimulated renin production was not inhibited by Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Mar
PMID:Effect of angiotensin II on renin production by rat adrenal glomerulosa cells in culture. 131 12

In deoxycorticosterone acetate (DOCA)-NaCl hypertension, the effects of vasopressin (VP) in the cortical collecting tubule (CCT) are exaggerated. These include both the biochemical effect of VP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in the CCT and physiological effects of VP-mediated sodium and water retention. In this study, we examined the mechanism of enhanced VP-stimulated cAMP formation in the CCT. We compared cAMP formation in response to activators (following in parentheses) of the VP receptor (VP), of the stimulatory guanine nucleotide binding (Gs) protein [guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S); F-], and of the catalytic subunit of adenylyl cyclase (forskolin, Mn2+) between control and DOCA-NaCl-treated rats. The effects of VP and forskolin were enhanced in CCT of DOCA-NaCl-treated animals by 201 and 139%, respectively, compared with control animals. Other activators, Mn2+ (150%), F- (142%), and GTP gamma S (156%), also caused augmented cAMP formation in the CCT of DOCA-NaCl-treated rats. The DOCA-NaCl-induced increment in cAMP response to VP remained after pretreatment of the rats with pertussis toxin (171 and 169% increase in response in DOCA-NaCl and control rats, respectively), suggesting that altered inhibitory guanine nucleotide binding (Gi) protein function is not the mechanism for the altered response to VP in the CCT. Further evidence that Gi function is intact in DOCA-NaCl animals is that epinephrine (via alpha 2-adrenoceptor stimulation) inhibited VP-stimulated cAMP accumulation to a similar degree in DOCA-NaCl and control rats (86 and 76%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:DOCA-enhanced sites of vasopressin-stimulated cAMP formation in rat cortical collecting tubule. 133 10

Nitric oxide (NO) and atrial natriuretic factor (ANF) cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP) via activation of the soluble and particulate guanylate cyclases, respectively. The chronic effects of NG-nitro-L-arginine methyl ester (L-NAME), an L-arginine antagonist and NO synthase inhibitor, on the blood pressure and plasma and aortic cGMP levels of rats were tested. Wistar rats (n = 10 per group) were given doses of L-NAME (0, 1, 5, 10, 20, 50, and 100 mg/kg.d) by gavage twice a day for 4 wk. Chronic L-NAME induced a time- and dose-dependent increase in blood pressure. The total heart weight/body weight ratio did not change in any group, despite the hypertension. The plasma levels of cGMP did not change significantly in any group, and were correlated with the plasma ANF levels (r = 0.51, P less than 0.0001). Aortic cGMP decreased in negative correlation with increasing L-NAME from 0 to 10 mg/kg.d, culminating in a 10-fold drop arterial wall cGMP. The aortic cGMP content of rats in the four highest dose groups (from 10 to 100 mg/d) tended to increase slightly and was positively correlated with endogenous ANF (r = 0.48, P less than 0.002, n = 40). Intravenous L-arginine decreased arterial blood pressure and reversed the decline in aortic cGMP. Exogenous ANF and sodium nitroprusside both significantly increased aortic cGMP. Neither the arterial wall concentrations of cGMP-dependent kinase nor cAMP was changed by L-NAME. Thus, chronic blockade of NO synthase with L-NAME induces a dose-dependent increase in blood pressure and decrease in aortic cGMP. The in vivo basal aortic cGMP seems to be mainly dependent on NO synthase: soluble guanylate cyclase activity and to a minor extent on particulate guanylate cyclase activity.
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PMID:Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase. 137 15

Prostacyclin (PGI2) is known to cause vasorelaxation and inhibit platelet aggregation by receptor-mediated mechanisms. While cyclic (c) AMP is known to act as a second messenger for inhibition of platelet aggregation, vasorelaxation by hyperpolarization has been described only recently and may provide an explanation, in addition to stimulation of cAMP for the PGI2 mechanism of action on blood vessels. When PGI2 is infused into healthy volunteers it reduces blood pressure only at infusion rates that also cause significant side-effects, primarily, nausea, emesis, flushing, diaphoresis, and restlessness. In hypertensive patients blood-pressure responses are complex and are influenced to some extent by renin secretion. PGI2 stimulates renin secretion by a direct effect on the juxtaglomerular apparatus, and it also has an indirect effect by activating the sympathetic nervous system. Thus, it is useless as an antihypertensive agent even apart from its debilitating side-effects. Vascular PGI2 is synthesized endogenously by both the endothelial cells and the muscularis of arteries. While the endothelial cells undoubtedly synthesize large amounts of PGI2, the muscularis comprises a much larger tissue mass so that the overall synthesis is about equally distributed between the endothelial and muscle cells. In patients with pregnancy-induced hypertension and some patients with essential hypertension endogenous synthesis of PGI2 has been evaluated by measuring 2,3-dinor-6-keto-PGF1 alpha and has proved to be greatly reduced. Some drugs (thiazides, propranolol) have been shown to stimulate PGI2 synthesis, and inhibition of cyclooxygenase has been shown to reduce their antihypertensive effects. The effects of low- and high-dose aspirin on prostacyclin and thromboxane synthesis are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Prostacyclin in hypertension]. 149 51

Dopamine is an endogenous catecholamine that modulates many functions including behavior, movement, nerve conduction, hormone synthesis and release, blood pressure, and ion fluxes. Dopamine receptors in the brain have been classically divided into D1 and D2 subtypes, based on pharmacological data. However, molecular biology techniques have identified many more dopamine receptor subtypes. Several of the receptors cloned from the brain correspond to the classically described D1 and D2 receptors. Several D1 receptor subtypes have been cloned (D1A, D1B, and D5) and are each coupled to the stimulation of adenylyl cyclase. The D2 receptor has two isoforms, a shorter form, composed of 415 amino acids, is termed the D2short receptor. The long form, called the D2long receptor, is composed of 444 amino acids; both are coupled to the inhibition of adenylyl cyclase. The D3 and D4 receptors are closely related to, but clearly distinct from, the D2 receptor. They have not yet been linked to adenylyl cyclase activity. Outside of the central nervous system, the peripheral dopamine receptors have been classified into the DA1 and DA2 subtypes, on the basis of synaptic localization. The pharmacological properties of DA1 receptors roughly approximate those of D1 and D5 receptors, whereas those of DA2 receptors approximate those of D2 receptors. A renal dopamine receptor with some pharmacological features of the D2 receptor but not linked to adenylyl cyclase has been described in the renal cortex and inner medulla. In the inner medulla, this D2-like receptor, termed DA2k, is linked to stimulation of prostaglandin E2 production, apparently due to stimulation of phospholipase A2. Of the cloned dopamine receptors, only the mRNA of the D3 receptor has been reported in the kidney. The DA1 receptor in the kidney is associated with renal vasodilation and an increase in electrolyte excretion. The DA1-related vasodilation and inhibition of electrolyte transport is mediated by cAMP. The role of renal DA2 receptors remains to be clarified. Although DA1 and DA2 receptors may act in concert to decrease transport in the renal proximal convoluted tubule, the overall function of DA2 receptors may be actually the opposite of those noted for DA1 receptors. Dopamine has been postulated to act as an intrarenal natriuretic hormone. Moreover, an aberrant renal dopaminergic system may play a role in the pathogenesis of some forms of hypertension. A decreased renal production of dopamine and/or a defective transduction of the dopamine signal is/are present in some animal models of experimental hypertension as well as in some forms of human essential hypertension.
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PMID:The renal dopamine receptors. 162 51


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