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

It has been demonstrated that somatostatin (SRIF) can suppress hypophyseal and extrahypophyseal hormones; moreover, many studies have shown that SRIF inhibits frusemide-induced hyperreninemia in normal man, and renin and aldosterone in renovascular hypertension, possibly through a beta-adrenergic block. To further investigate the possible aldosterone-inhibiting effect of somatostatin, we have carried out in vitro studies using isolated perfused rat zona glomerulosa cells suspended in Bio-gel. Paired columns were set up and the cells stimulated using either angiotensin II, ACTH, serotonin or potassium. One column was perfused with somatostatin (3-4 ng/ml) and the other was used as a control. Aldosterone was measured by highly specific direct radioimmunoassay. Somatostatin significantly blocked the aldosterone response to angiotensin II but not to ACTH, serotonin or potassium. The inhibitory effect of somatostatin persisted as long as it was added to the medium; the aldosterone response to angiotensin II was progressively restored after discontinuation of the SRIF infusion. From these data it might be suggested that the inhibitory effect of somatostatin on aldosterone production is not cAMP-dependent, since ACTH maintains its stimulatory capacity. The recent demonstration of the presence of specific somatostatin receptors on the rat adrenal cells suggests that its inhibitory effect could be mediated by the second messenger system rather that the interaction with angiotensin II receptors.
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PMID:Inhibitory effect of somatostatin on the aldosterone response to angiotensin II: in vitro studies. 612 38

Adenosine 3',5'-cyclic monophosphate (cAMP) metabolism was studied in the microcirculation (100- to 150-micrometers arterioles) of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) at different stages of hypertension. Mesenteric arterioles from animals 4, 6, 12, and 18 wk old were incubated in Krebs-Ringer bicarbonate buffer for 30 min at 37 degrees C, pH 7.4, with and without the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (MIX). cAMP was assayed by radioimmunoassay. Arteriolar production of cAMP was age related in both WKY and SHR rats although the temporal patterns were different. At 6 wk (developmental stage of hypertension in SHR) cAMP accumulation in the presence or absence of MIX by SHR arterioles was higher than in the WKY before falling to normotensive levels at 12 wk. Salbutamol (a beta 2-agonist) stimulated dose-dependent increases in cAMP in both WKY and SHR at 6 wk. Stimulation of cAMP by salbutamol or by isoproterenol was blocked by propranolol. Neither agonist increased guanosine 3',5'-cyclic monophosphate. These data indicate that differences in cAMP metabolism are evident at the arteriolar level during the developmental stage of SHR hypertension. These differences may contribute to the morphological and physiological changes occurring at this time.
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PMID:Elevated arteriolar adenosine 3',5'-cyclic monophosphate production by SHR. 618 Jun 47

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were compared for phosphorylation-dephosphorylation mechanism(s) in aorta, caudal artery, inferior vena cava, and right and left ventricles. Reduction of cAMP-induced phosphorylation of microsomes and cAMP-dependent protein kinase activity was significant in the aorta and caudal artery of SHR compared with WKY. These changes were not observed in the vena cava of SHR. Phosphoprotein phosphatase activity was significantly increased (p less than 0.05) in the soluble fraction of arterial smooth muscle. No changes were observed, however, in the myocardium or vein. Furthermore, the extent of phosphorylation, and Ca2+ uptake ability and the protein kinase activity in the soluble and the microsomal fractions were not reduced in the myocardium of SHR compared with WKY. These data suggest that phosphorylation-dephosphorylation mechanisms are altered in the microsomal fraction of the aorta and caudal artery of SHR, which may result in reduced Ca2+ uptake by the intracellular organelle. The changes observed could have a significant effect on vasodilatation of arteries in the hypertensive state. The lesion appears specific to the arterial smooth muscle in the cardiovascular tissues.
Hypertension
PMID:Possible role of phosphorylation-dephosphorylation in the regulation of calcium metabolism in cardiovascular tissues of SHR. 624 68

Plasma cAMP was determined using the method of Tovey et al. in normal pregnant women with a mean concentration of 18.9 +/- 0.8 pmol/ml (x- +/- SEM). Between weeks 9-12 and 33-36 of gestation, there were two peaks, with a mean cAMP of 22.5 +/- 2.4 which were significantly increased in comparison to the other weeks of pregnancy. Significantly decreased values were found in patients with threatened abortion (weeks 12-28) which terminated in abortion (11.6 +/- 2.4; p < 0.01). In premature labor no differences were found. During therapy with fenoterol there were highly significantly increased plasma cAMP levels (48.2 +/- 2.8; p < 0.0005). During thyroid hormone therapy in euthyroid goiter, cAMP was significantly decreased (14.0 +/- 1.4; p < 0.05). 1 week after cessation of therapy a highly significant increase of cAMP was observed (38.2 +/- 6.9; p < 0.0005). There was a negative linear regression between T3 and cAMP (2p < 0.01). In pregnancy with hypertension cAMP was significantly elevated (30.5 +/- 3.8 p < 0.0005), but nearly normal under antihypertensive therapy. In pregnancy with edema only, no difference was found. Induction of labor with PGE2 alpha was followed by a decrease of plasma cAMP.
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PMID:Plasma cAMP in normal and abnormal human pregnancy. 625 65

Accumulation of cAMP induced by noradrenaline (NA) was higher in the medulla oblongata (MO) of hypertension-prone (H) than in resistant (N) rats, 113 +/- 3 vs. 72 +/- 4 (p less than 0.01). In the hypothalamus (HYP) it was higher in N than in H rats, 148 +/- 8 vs. 92 +/- 6 (p less than 0.01). In both anterior and posterior HYP, the accumulation of cAMP was significantly higher in N than in H rats. cAMP accumulation, in the presence of increasing concentrations of phosphodiesterase inhibitor, showed significant strain differences in both MO and HYP. The observed strain differences in cAMP may be pertinent to the disparate susceptibility to hypertension of H and N rats.
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PMID:Cyclic AMP generation in medulla oblongata and hypothalamus of hypertension-prone and -resistant rats. 625 86

Tonin is an enzyme of the serine protease family present in different rat tissues which releases angiotensin II (AII) directly from angiotensinogen and the tetradecapeptide renin substrate and from angiotensin I (AI). Tonin potentiates the effect of norepinephrine (NE) in the rat mesenteric artery preparation and in the aortic strips from normal and hypertensive rats. In rabbit aortic and mesenteric artery strips tonin potentiates the effect of NE, almost doubling its response. A similar effect was observed on the KCl and AII-induced contraction. This tonin-induced potentiation is reversible and long-lasting, persisting for 1 to 2 hours after being added into the tissue bath. In 75% of the vascular strips assayed, tonin elicited a contraction with a short latency period and with a maximum tension ranging from a few milligrams to over 1 g. To clarify the mechanisms of tonin effect on vascular smooth muscle, a variety of agents have been used. Neither indomethacin, saralasin, nor alpha- or beta-adrenergic blockers changed the direct contraction or the potentiation induced to NE. Db-cAMP and theophylline blocked the potentiation to the response to NE. A Ca2+-free medium, La3+, and verapamil produced a 75% inhibition of the direct tonin-induced contraction. Papaverine, isoproterenol, and theophylline relaxed the same contraction. Enzymatic inactivation of tonin blocked completely the direct contraction but not the potentiation to NE. These experiments suggest that the vasoactive effect of tonin may be mediated by the release of intracellular-bound calcium, an effect dependent on a proteolytic effect of tonin, and by increasing the cellular permeability to calcium, which is not of a proteolytic effect. It is suggested that tonin remains attached to the vascular strips by mechanisms as yet not clarified.
Hypertension
PMID:Effects of tonin, an angiotensin II-forming enzyme, on vascular smooth muscle in the normal rabbit. 626 53

Sodium nitroprusside (NP) is a potent vasodilator that also inhibits platelet aggregation. To test the hypothesis that NP causes both of these effects by altering the balance between prostacyclin (PGI2) produced by endothelial cells and thromboxane A2 (TXA2) produced by platelets, we incubated each of these cell types with NP for 5 minutes and assayed the PGI2 and TXA2 produced. NP at pharmacologically achieved doses (0.01--30 micrograms/ml) inhibited platelet aggregation and resultant TXA2 synthesis in a dose- and time-dependent manner (p less than 0.001). The inhibition was not dependent on cAMP production, external calcium concentration, or suppression of TXA2 synthesis. NP did not alter the production of PGI2 by cultured human endothelial cells as measured by radioimmunoassay for 6-Keto-PGF1 alpha, the stable hydrolysis product of PGI2. However, supernates of NP-treated endothelial cells containing low, noninhibitory concentrations of NP unexpectedly inhibited platelet aggregation. This inhibition of platelet aggregation was due to synergy between PGI2 (0.1--3 nM) and NP (p interaction less than 0.03). The synergistic inhibition by NP and PGI2 of platelet aggregation and TXA2 synthesis in vivo may explain some of the beneficial actions of NP in the treatment of hypertension and congestive heart failure.
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PMID:The interaction of sodium nitroprusside with human endothelial cells and platelets: nitroprusside and prostacyclin synergistically inhibit platelet function. 629 3

The effect of varying the amount of dietary magnesium on the development of hypertension in spontaneously hypertensive (SH) rats was investigated with three diets containing 1.05% (H1Mg diet), 0.52% (H2Mg diet), and 0.008% (LMg diet). The control group was given a diet containing a normal amount of magnesium (0.2%). When the diet was sufficiently supplemented with magnesium (H1Mg diet), the development of hypertension was significantly slowed and the heart rate slightly lowered. With dietary magnesium depletion (LMg diet), the heart rate was accelerated and hypertension developed more rapidly. Excretion of urinary electrolytes (calcium, magnesium, and sodium) was increased by rats fed the H1Mg diet and decreased by rats on the LMg diet. Urinary cAMP was decreased both on the HMg diets and on the LMg diet. With the H1Mg diet, total and ionized calcium and sodium levels in plasma fell, and magnesium plasma levels rose. Rats fed the LMg diet had increased total and ionized calcium and decreased magnesium plasma levels. These results show that dietary magnesium modifies the metabolism of calcium, sodium, magnesium, which can modulate the development of genetic hypertension.
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PMID:Effects of dietary magnesium on the development of hypertension in the spontaneously hypertensive rat. 631 30

PTH causes dose dependent transient vasodilatation in various vascular beds, specifically renal, coeliac, coronary, but not osseous. It has an acute dose-dependent hypotensive effect in the intact animal which is not mediated by alpha- or beta-adrenergic, cholinergic or histaminergic mechanisms. Aortic medial smooth muscle cells respond to PTH with an increase of cAMP, cGMP and, presumably via protein kinase, with activation of phosphorylase B kinase. The acute vasodilatory effect of PTH is antagonised by indomethacin and diclofenac as well as by ouabain, suggesting that the membrane Na-K pump and prostaglandins are involved in PTH-induced vasodilatation. Parathyroidectomy and a high calcium diet attenuate the rise of arterial pressure in experimental hypertension, pointing to some permissive effect of PTH for development hypertension. This is most likely due to long term effects of PTH on vessel wall calcium content and exchange. This chronic effect of PTH may explain the high prevalence of hypertension in patients with primary hyperparathyroidism.
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PMID:Vascular effects of parathyroid hormone (PTH). 675 27

In the present investigation 238 randomly selected male individuals of the general population (age 19--41 years) and 42 age-matched male patients with recurrent renal stone formation (calcium oxalate and/or calcium phosphate) were studied under outpatient conditions without dietary restrictions. Urinary Na excretion was 207 +/- 82 mmol/24 h (range 55--570) in controls and 208 +/- 100 (range 76--575) in recurrent renal stone formers. Both in controls (r = 0.36; p less than 0.01) and in stone formers (r = 0.4; p less than 0.01) a significant correlation was observed between urinary excretion of sodium and calcium. Urinary sodium excretion was unrelated to systolic or diastolic blood pressure in normotensive or hypertensive individuals. This finding indicates that factors other than sodium are involved in the maintenance of hypertension. Urinary sodium, presumably an index of intake of nutrients, was significantly correlated to several coronary risk factors, e.g. fasting glucose, cholesterol and overweight. There existed a significant inverse relationship between fasting plasma phosphate and urinary sodium, but not between fasting plasma phosphate and serum iPTH or urinary cAMP. This finding points to some function of sodium excretion as one determinant of plasma phosphate.
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PMID:Urinary sodium excretion in renal stone formers. An epidemiological study. 739 37


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