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

We designed experiments to reveal the antihypertensive properties of cicletanine, a novel antihypertensive drug, in Dahl salt-sensitive (Dahl-S) rats. Cicletanine (39 mg/kg body weight per day for 6 weeks) ameliorated the development of hypertension in Dahl-S rats fed a high-salt (4% NaCl) diet. This blood pressure reduction was associated with a decrease in heart weight and vascular wall thickness. Moreover, urinary prostacyclin (PGl2) excretion was increased with cicletanine treatment, being inversely related to systolic blood pressure. Proteinuria and urinary excretion of n-acetyl-beta-D-glucosaminidase were decreased and glomerular filtration rate was increased with this treatment. Morphological investigation revealed an improvement in glomerulosclerosis, renal tubular damage and intrarenal arterial injury in the salt-induced hypertensive rats. In contrast, trichloromethiazide, which decreased blood pressure to the same extent as cicletanine, lowered urinary PGl2 excretion and generally did not ameliorate the deteriorated renal functions and morphological abnormalities. Thus, these data indicate that cicletanine ameliorates the development of hypertension in Dahl-S rats and protects the cardiovascular and renal systems against the injuries seen in the hypertension. The enhanced vasodepressor PGl2 synthesis probably participates, to some extent, in these beneficial properties of long-term cicletanine treatment.
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PMID:Antihypertensive effects of cicletanine and renal protection in Dahl salt-sensitive rats. 165 82

Results from several studies suggest that beta-adrenoceptor blockade causes increased biosynthesis of the vasodilator prostanoid prostacyclin in the arterial wall. This effect may contribute to the clinical effects of beta-blockers in hypertension and coronary heart disease. Studies in hypertensive patients and in animals indicate that the arterial pressure reduction after beta-blockade is related to the associated increase of prostacyclin biosynthesis, regarding both magnitude and time of onset of effect. Some observations suggest that the effects of beta-blockers in myocardial ischemia may in part be due to an improvement of coronary blood flow caused by increased prostacyclin biosynthesis.
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PMID:Prostacyclin synthesis in relation to sympathoadrenal activation. Effects of beta-blockade. 168 9

The roles of fibrinolysis, fibrinogen, and plasminogen activator inhibitor-1 in the development of coronary heart disease are reviewed, and possible effects of long-term treatment with beta-blockade are discussed. Decreased fibrinolysis is associated with coronary artery disease, and coronary thrombus formation is the most frequent event precipitating myocardial infarction. Recently, it has also been shown that high levels of fibrinogen and plasminogen activator inhibitor-1 are predictors for myocardial infarction. Because beta-blockers are used to treat hypertension, angina, and myocardial infarction, it is important to determine the impact of beta-blockers on fibrinolysis. Several factors influence fibrinolysis. Some forms of stress and epinephrine infusions increase fibrinolysis, probably by stimulating beta 2-adrenoceptors. Nonselective beta-blockers may adversely affect this process, whereas beta 1-selective antagonists and those with intrinsic sympathomimetic activity may not. Since prostacyclin synthesis is correlated to increased fibrinolytic activity and since beta-blockers may moderate stress-induced reductions in prostacyclin formation, beta-blockers may have the potential to exert a beneficial effect on fibrinolysis in chronic stress situations. The net effect of beta-blockade is not easily predicted and probably depends on the nature of the stress (whether it is acute or chronic), the status of the patient, and the selectivity of the beta-blocker. Nevertheless, it remains a possibility that beta-blockers may exert a positive therapeutic effect in relation to coronary thrombosis by an action on fibrinolytic mechanisms.
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PMID:Fibrinogen and plasminogen activator inhibitor-1 levels in hypertension and coronary heart disease. Potential effects of beta-blockade. 168 12

For humans, ecological and epidemiological results are reported that show a relationship between the serum selenium concentration and cardiovascular disease in populations where low serum selenium concentrations are found, e.g., in Eastern Finland. From clinical studies done in Germany (FRG and GDR), Finland, and Sweden, subnormal serum selenium and partially whole blood selenium concentrations are reported in patients with acute myocardial infarction. For patients with coronary arteriosclerosis, subnormal serum selenium concentrations are reported from the USA and Germany and subnormal whole blood selenium concentrations from Germany. Subnormal serum and subnormal whole blood selenium concentrations of patients with cardiomyopathy are reported from non Keshan disease affected areas in Germany, France, and China. In selenium deficiency, an accumulation of lipid peroxides in the heart may occur, especially under ischemic conditions and if ischemic tissue is reperfused. Lipid peroxides in the heart may damage the cell membrane and may lead to an impaired calcium transport with an uncontrolled calcium accumulation in the cell. This may result in an activation of phospholipids, and, in consequence, to an enhanced formation of arachidonic acid. An increased concentration of lipid peroxides owing to selenium deficiency may shift the prostaglandin synthesis from prostacyclin to thromboxane, causing enhanced blood pressure and platelet aggregability. From animal experiments, it is known that selenium protects against cardiotoxic elements, cardiotoxic xenobiotics, and viral infections that affect the heart. Selenium deficiency may also be a secondary factor in the causation of hypertension and myocardial ischemia.
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PMID:Selenium and cardiovascular disease. 170 69

A better understanding of the hemodynamic abnormalities in gestational hypertension together with the use of effective antihypertensive agents have resulted in more rational therapeutic approaches and a substantial improvement in maternal and fetal welfare. In normal pregnancy, there is reduced vascular reactivity with peripheral pooling and decreased circulatory responses to pressor agents. These are prostacyclin-dependent processes. In gestational hypertension, the normal increase in plasma volume and cardiac output with pregnancy is attenuated and prostacyclin-dependent processes are impaired, resulting in persistent vasoconstriction, enhanced responses to pressor agonists, and failure to develop adequate uteroplacental interchange. Among the modern antihypertensive agents, alpha- and beta-adrenergic antagonists and calcium ion entry blockers have permitted safe and effective long-term blood pressure control with sustained fetal growth. The development of proteinuria that can occur in chronic hypertension or in previously normotensive women (toxemia of pregnancy) can be prevented by the use of beta-adrenergic blocking agents and possibly by low-dose aspirin (75 mg/day). Maternal prostacyclin-thromboxane imbalance, important in the pathogenesis of gestational hypertension, is corrected by low-dose aspirin treatment. With the prevention of pre-eclampsia, the adverse maternal and fetal prognosis in gestational hypertension has been improved.
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PMID:Treatment of hypertension in pregnancy. 170 7

1. Platelet activation in vivo occurs in healthy pregnant women and is more marked in women with preeclampsia. During pregnancy platelets have also been shown in vitro to be less susceptible to the inhibitory effects of prostacyclin. The cyclic nucleotide cyclic AMP has a key role as an inhibitory second messenger in platelets and mediates the inhibitory effects of prostacyclin. 2. We have studied cyclic AMP in relation to platelet behaviour in healthy pregnant women in the third trimester and in women with pregnancy-induced hypertension and pre-eclampsia. Non-pregnant young women were used as controls. 3. Pharmacological agents which increase levels of cyclic AMP were significantly less effective as inhibitors of platelet activation during pregnancy, but there was no difference between the healthy and hypertensive pregnant subjects. 4. Basal platelet cyclic AMP levels were the same in all three groups. However, the production of cyclic AMP in response to a range of adenylate cyclase stimulators was reduced during pregnancy, but again there was no difference between healthy and hypertensive pregnant subjects. 5. The reduction in platelet cyclic AMP levels in pregnancy occurred not only with those adenylate cyclase stimulators which operate via surface receptors, but also on direct stimulation of the enzyme with forskolin. 6. The most likely explanation of these observations is a reduction in the ability of the platelet adenylate cyclase enzyme to respond to stimulation of the third trimester of pregnancy. The consequent reduction in formation of the inhibitory second messenger cyclic AMP may in part be responsible for platelet activation in vivo during pregnancy. There does not appear to be a further difference in platelet cyclic AMP production in hypertensive pregnant women.
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PMID:A cross-sectional study of platelet cyclic AMP in healthy and hypertensive pregnant women. 171 45

An effect of the specific thromboxane A2 synthetase inhibitor and stable prostacyclin analogue on arterial blood hypertension was investigated in 12 patients with spontaneous hypertension of II degree and in 12 healthy subjects. The patients were given a 3-hour intravenous infusion of Iloprost (Schering) in the dose of 2 ng/kg b.w. per minute and OKY-046 (ONO, Japan) in a single oral dose of 400 mg. Iloprost shortened euglobin fibrinolysis time without an effect on tissue plasminogen activator levels or blood pressure. OKY-046 decreased TBX2 to undetectable values, increased 6-keto-PGF1 alpha by 8-fold, and significantly reduced both systolic and diastolic blood pressures in hypertensive patients. Such effects may dependent upon an increase in the endogenous prostacyclin or an inhibition in thromboxane production in the affected arterial walls. If the present observations would be confirmed by double blind trial, they would constitute the base for new pharmacotherapy of hypertension.
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PMID:[Effect of thromboxane A2 synthetase inhibitor and prostacyclin analogue on arterial blood pressure, fibrinolysis and platelet function in patients with hypertension]. 172 88

The objective of this study was to test the hypothesis that the vasodilator prostaglandins E2 (PGE2) and PGI2) participate in the mechanisms involved in the increased renal vascular reactivity (RVR) observed in genetic hypertension. Studies were performed on anesthetized young and adult spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Renal blood flow (RBF) was measured during bolus injections into the renal artery of different doses of viprostol and iloprost (stable receptor agonists of PGE2 and PGI2, respectively) before and during inhibition of prostaglandin synthesis by indomethacin. Under control conditions, PGE2 increased RBF equally in young SHR and WKY. However, after cyclooxygenase inhibition the PGE2-induced increase in RBF was larger in young SHR than in WKY. Adult SHR displayed reduced reactivity to PGE2 relative to age-matched WKY under control conditions. This strain difference was abolished after indomethacin administration. PGI2 increased RBF slightly in young rats before and after indomethacin administration. In contrast, both strains of older animals displayed significant increases in RBF in response to PGI2 injections. Indomethacin administration enhanced this PGI2-induced relaxation in adult SHR but not WKY. We propose that the action of vasodilator PGs in the renal vasculature of rats developing hypertension may be limited by low density of their renal receptors and/or the opposing action of vasoconstrictor PGs. As age advances, PGI2 seems to be activated, possibly as part of a regulatory response to counterbalance the increased renal vascular resistance following the establishment of the disease.
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PMID:Renal vascular reactivity to vasodilator prostaglandins in genetically hypertensive rats. 173 88

Angiotensin II stimulates prostaglandin release in blood vessels via activation of angiotensin receptors present in endothelium, vascular smooth muscle cells, or both. We evaluated the response of angiotensin II, angiotensin I, and [des-Phe8] angiotensin II [angiotensin-(1-7)] on prostaglandin release in porcine aortic endothelial cells. Incubation of cell monolayers with angiotensin I and angiotensin-(1-7), but not angiotensin II, stimulated the release of prostaglandin E2 and prostaglandin I2 in a dose-dependent manner (10(-10) to 10(-6) M) with an EC50 of approximately 1 nM. In addition, we characterized the angiotensin receptor subtypes mediating prostaglandin synthesis by using subtype-selective antagonists. Angiotensin I-stimulated prostaglandin synthesis was not altered by either of the nonselective classical angiotensin receptor antagonists [Sar1,Thr8]angiotensin II or [Sar1,Ile8]angiotensin II. In contrast, either the angiotensin subtype 1 (AT1) antagonist DuP 753 or the subtype 2 (AT2) antagonist CGP42112A significantly attenuated the prostaglandin release in response to angiotensin I. However, PD123177, another AT2 antagonist, did not inhibit angiotensin I-stimulated prostaglandin release. Angiotensin-(1-7)-induced prostaglandin release was significantly attenuated by [Sar1,Thr8]angiotensin II (10(-6) M) and PD123177 (10(-6) M) but not by [Sar1,Ile8]angiotensin II, DuP 753, or CGP42112A. Higher doses (10(-5) M) of DuP 753 and CGP42112A attenuated the angiotensin-(1-7) response. These data suggest that in porcine aortic endothelial cells, angiotensin I and angiotensin-(1-7) but not angiotensin II are potent stimuli for prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors. 173 95

Although endothelium-derived prostaglandin I2 stimulates renin release, exogenous endothelium-derived relaxing factor (EDRF) can inhibit it. To characterize the role of EDRF as an endogenous regulator of renin release, we inhibited or stimulated its production in rat renal cortical slices in vitro. Renin concentration in the incubation medium was determined by radioimmunoassay for angiotensin I (Ang I) generation. NG-Monomethyl-L-arginine (LNMMA) (10(-4) M), which blocks EDRF formation, significantly enhanced basal renin release from kidney slices by more than 50% in control medium (40.0 +/- 14.3 ng Ang I/hr/mg/30 min; p less than 0.01) or in medium treated with 1.6 x 10(-5) M meclofenamate (50.8 +/- 8.4 ng Ang I; p less than 0.025). Isoproterenol (10(-5) M)-stimulated renin release (40.0 +/- 14.3 ng Ang I; p less than 0.02) was not modified by LNMMA; addition of L-arginine (10(-5) M), the precursor of EDRF, did not change basal but blocked isoproterenol stimulation of renin. Nitroprusside (10(-5) M) completely reversed melittin-stimulated renin release. Endothelin-1, an endothelium-derived vasoconstrictor, inhibits renin release and stimulates EDRF and prostaglandin synthesis. To determine whether any of the renin-inhibiting effect of endothelin-1 was due to its stimulation of EDRF, we compared the effect of endothelin-1 on cortical slices with and without EDRF inhibition. Endothelin-1 (10(-7) M) decreased renin by 36.7 +/- 10.9 ng Ang I (p less than 0.01) compared with controls, and the response was the same after either LNMMA or hemoglobin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Nonprostanoid endothelium-derived factors inhibit renin release. 173 97


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