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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently reported that a low dose dopamine (DA) infusion in normal subjects increased renal blood flow (RBF) via prostacyclin (PGI2) formation without changes in PGE2 levels. The present study explores whether this mechanism is mediated by the DA1 receptor and evaluates the effect of DA on RBF and PGs in subjects with essential hypertension (EH). A low dose of DA (1 microgram/kg.min), which previously did not alter hemodynamics in normal subjects was infused into eight patient with EH to determine the role of DA stimulation in hypertensives. To assess the effect of DA1 stimulation, fenoldopam, a selective DA1 agonist, was infused (0.1 microgram/kg.min) into 10 normal and 10 hypertensive patients. Fenoldopam, unlike DA, significantly decreased diastolic blood pressure in hypertensives (96 +/- 3 to 85 +/- 2 mm Hg; P less than 0.01) along with a significant increase in pulse rate (68 +/- 2 vs. 73 +/- 2 beats/min; P less than 0.01). RBF measured by para-aminohippurate clearance increased only in normals during fenoldopam infusion from 1185 +/- 71 to 1533 +/- 84 L/min.m2 (PGI(2)01), and this was associated with an increase in PGI2 (6-keto-PGF1) excretion (149 +/- 19 vs. 214 +/- 32 ng/g creatinine; P less than 0.02). These effects of fenoldopam were similar to DA effects on RBF and PGI2 excretion in normals. In contrast, in hypertensive subjects, neither fenoldopam (867 +/- 113 vs. 1054 +/- 177 L/min.m2; P greater than 0.1) nor DA (1098 +/- 85 vs. 1061 +/- 101 L/min.m2; P greater than 0.1) increased RBF. Similarly, neither the DA nor the fenoldopam infusion stimulated PGI2 excretion in the hypertensives. The fenoldopam infusion in the hypertensives produced a significant natriuresis (22 +/- 3 to 49 +/- 9 mmol/3 h; P less than 0.05). Similar effects on Na+ excretion in this group were noted during DA infusion (17 +/- 3 to 36 +/- 3 mmol/3 h; P less than 0.05), suggesting that DA-induced natriuresis is not directly linked to DA-induced changes in RBF or PG excretion. The present study shows that in normal subjects, fenoldopam, a specific DA1 agonist, like DA, stimulates renal PGI2 release and RBF. In contrast, neither DA nor fenoldopam alters PGI2 or RBF in patients with EH, suggesting an alteration of dopaminergic tone in some hypertensives that is characterized by a defect in DA1 receptor sensitivity.
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PMID:Comparison of dopamine and fenoldopam effects on renal blood flow and prostacyclin excretion in normal and essential hypertensive subjects. 257 13

In young patients with borderline arterial hypertension the system of pressor and depressor prostaglandins (PG) is activated with maintenance of their physiological proportion. In patients with I stage essential hypertension a considerable rise in the level of PGF2 alpha and thromboxane determines the system imbalance in the direction of the predominance of pressor components. The platelet hemostatic link in I stage essential hypertension is characterized by an increase in platelet aggregation activity which is mediated by the imbalance of the prostacyclin-thromboxane system in the direction to thromboxane.
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PMID:[Thrombocytic hemostasis and the prostaglandin system at early stages of arterial hypertension]. 275 63

The effects of enalapril alone and in combination with the cyclooxygenase inhibitors sulindac and indomethacin on blood pressure (BP), plasma aldosterone, renin activity and converting enzyme activity were evaluated in 29 patients with mild to moderate essential hypertension, 26 of whom had low plasma renin activity. Patients were randomly assigned to one of three treatment groups. All patients underwent a 4-week placebo phase (phase I), then received enalapril (20 mg BID) for 4 weeks (phase II). In phase III, group I (n = 10) continued on enalapril alone; group II (n = 9) received sulindac 200 mg BID plus enalapril, and group III (n = 10) received indomethacin 50 mg BID plus enalapril, all for 4 weeks. Enalapril lowered BP significantly (mean supine BP 149/100 in phase I vs. 134/90 in phase II, p less than 0.05) without inhibiting aldosterone production. The BP effect was not blunted by concomitant administration of sulindac or indomethacin. Enalapril lowered converting enzyme activity to 25% to 30% of baseline and tended to increase renin activity. In the 10 patients who received indomethacin (group III), the effects of enalapril alone and enalapril plus indomethacin on urinary excretion of 6-keto prostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin (PGI2), were examined. Enalapril increased urinary 6-keto PGF1 alpha in group III from 118 +/- 23 to 194 +/- 38 ng/g creatinine (p less than 0.05), while addition of indomethacin reduced 6-keto PGF1 alpha to basal levels (138 +/- 26 ng/g creatinine).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antihypertensive effect of enalapril in essential hypertension: role of prostacyclin. 282 71

In patients with essential hypertension plasma adrenaline concentrations have been found to be higher than in normotensive subjects and this may represent increased adrenergic activity. Adrenaline released into the circulation can be taken up by the sympathetic nerve ending and as it is re-released as a co-transmitter it enhances exocytotic noradrenaline release by stimulating prejunctional beta-adrenoceptors and as a consequence it contributes to postjunctional alpha 1-adrenoceptor-induced vasoconstriction. Adrenaline may also induce vasoconstriction via post- and extra-junctional alpha 2-adrenoceptors, as shown by a decrease in the forearm blood flow during adrenaline infusions in the postjunctional alpha 1- and beta-blocked forearm vasculature, an effect that could be antagonized by alpha 2-adrenoceptor blockade with yohimbine. alpha 2-Adrenoceptor stimulation in platelets showed an increased sensitivity to adrenaline, as determined by sensitivity in counteracting the inhibitor effect of PGI2 on intracellular free calcium concentration in untreated patients with essential hypertension, when compared with treated patients or normotensive subjects. As these effects can be normalized by antihypertensive treatment this suggests that the increased hormone sensitivity may be related to the elevated intracellular free calcium concentration. Thus adrenaline, via pre- and post-junctional adrenoceptors, may contribute to enhanced vascular smooth muscle contraction, which most likely is sensitized by the elevated intracellular calcium concentration.
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PMID:The adrenaline-alpha 2-adrenoceptor-mediated vasoconstrictor axis. 298 37

We tested the hypothesis that vascular prostacyclin synthesis is increased by propranolol and could account for some of the drug's antihypertensive effect. We studied 10 white patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin with or without the addition of propranolol on blood pressure and vascular prostacyclin biosynthesis, as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha), F1 alpha (PGF1 alpha), measured by gas chromatography-mass spectrometry. Seven patients responded to propranolol with a lowering of mean arterial blood pressure in both supine and upright postures. The fall in mean arterial blood pressure (-14.1 +/- 2.1 mm Hg sitting; -17.4 +/- 1.7 mm Hg supine) with propranolol alone was significantly greater than that produced when propranolol was given to patients receiving indomethacin (-7.8 +/- 1.9 mm Hg sitting; -7.7 +/- 3.0 mm Hg supine). Our drug-responsive patients demonstrated a significantly lower excretion rate of 2,3-dinor-6-keto-PGF1 alpha than was found in an age and sex-matched group of normal volunteers. With propranolol treatment, drug-responsive patients showed a significant increase in the excretion of 2,3-dinor-6-keto-PGF1 alpha, such that the mean excretion was not significantly different from that in normal volunteers. Indomethacin caused a significant rise in mean arterial blood pressure and a significant fall in 2,3-dinor-6-keto-PGF1 alpha excretion, and it blocked the rise in urinary 2,3-dinor-6-keto-PGF1 alpha associated with propranolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Propranolol increases prostacyclin synthesis in patients with essential hypertension. 306 Apr 30

The purpose of the study was to characterize the renal TxA2, PGI2 and PGF2 alpha release in response to arterial blood pressure (BP) fall induced by systemic and intrarenal vasorelaxation in subjects with essential hypertension. Significantly enhanced TxB2- and PGF2 alpha excretion and no change in ratio TxB2/6-keto-PGF1 alpha were found in urine in hypertensive patients after administration of the Ca++ entry blocker gallopamil, used to induce BP fall. This response was associated with significant PRA elevation in peripheral venous samples. In in vitro experiments, direct and indirect effects of gallopamil on renal tissue could be distinguished. Gallopamil resulted in significant diminution of TxA2 production and a decrease in TxB2/6-keto PGF1 alpha ratio in incubated rat kidney slices. This model was also used to test biochemically the effect of reflex sympathetic activation on prostanoid generation in kidney. It was concluded that this mechanism was only one among the indirect mechanisms by which gallopamil could induce that renal prostanoid response in hypertensive subjects. The response in urinary TxB2- and PGF2 alpha excretion was found to be significantly related to the changes in sodium reabsorption. These results suggested, that the increase in renal TxA2 and PGF2 alpha production in response to systemic and intrarenal "vasodilation" induced by gallopamil in hypertensive subjects can be interpreted as part of counteraction of the kidneys to BP fall.
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PMID:Prostanoid response in the kidney of hypertensive subjects as part of renal counteraction to gallopamil-induced blood pressure decrease. 307 78

Prostaglandins PGE2, PGD2, PGI2, and PGF2 alpha, as well as thromboxanes and leukotrienes, are synthesized by the fetal and neonatal kidney. The major prostaglandin, PGE2, PGD2, and PGI2, increase RBF, free water clearance, urine flow, and natriuresis. Alterations in the synthetic and catabolic activity of renal prostaglandins with advancing gestational and postnatal age occur along with concomitant alterations in RBF, GFR, and water and electrolyte excretion, suggesting that the prostaglandins play an important role in renal functional development. Indomethacin treatment may affect both fetal and neonatal renal function. Long-term maternal indomethacin treatment may decrease fetal urine output enough to alter amniotic fluid volume. Neonatal indomethacin therapy may cause transient dose-related renal dysfunction characterized by a decrease in urine output, but this renal dysfunction also depends in part on dosage, timing of therapy, and the cardiovascular and renal status of the infant prior to treatment. New areas of research interest include urinary prostaglandins as a marker for development of essential hypertension, and the possible interaction between antenatal steroids and renal function in the newborn.
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PMID:Prostaglandins and the developing kidney. 310 70

In normotensive and hypertensive humans, prostaglandins, particularly PGE2 and PGI2, affect blood pressure through control of vascular resistance, salt excretion, cardiac output, and renin secretion. The majority of studies of human essential hypertension have documented diminished renal synthesis and, hence, urinary excretion of PGE2. The acute administration of indomethacin inhibits prostaglandin synthesis and increases total peripheral resistance as well as mean blood pressure, with a countervailing decrease of cardiac index. The important vasodilatory and natriuretic roles of PGE2 and PGI2 are most apparent in hypertensive patients receiving antihypertensive therapy. The concomitant use of NSAID attenuates blood-pressure control in all reported studies using indomethacin. Consequently, potent NSAID should be avoided during treatment of hypertensive patients, and aspirin may be the safest NSAID in these circumstances. Interesting data are accumulating on the beneficial effects of polyunsaturated fatty acids, particularly linoleic acid and eicosapentaenoic acid, as dietary means to reduce blood pressure. All reported studies have documented small 5 to 10 mm Hg decrements of blood pressure with dietary supplementation with these fatty acids and conversion of the ratio of polyunsaturated to saturated fatty acids toward unity.
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PMID:The relevance of prostaglandins in human hypertension. 315

Plasma 6-Keto-Prostaglandin F1 alpha (6-Keto PG F1 alpha; stable hydrolysis product of prostacyclin) levels in 24 patients with essential hypertension and 15 age and sex matched healthy controls were studied. 6-Keto PG F1 alpha levels were measured in extracted plasma by radioimmunoassay using a commercial kit. The 6-Keto PG F1 alpha levels were significantly (P less than 0.001) higher in hypertensive patients as compared to controls. The raised levels of plasma 6-Keto PG F1 alpha in hypertensive patients may be an adaptive response of blood vessels to increased blood pressure.
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PMID:Prostacyclin in (extracted) plasma of essential hypertensives. 330 Jan 16

Aggregated platelets cause vasospasm in a perfused cat carotid artery, its severity increasing at the vessel's deendothelization and indomethacin treatment. Erythrocyte hemolysate also produced vascular contraction, which however diminished abruptly at de-endothelization or indomethacin treatment. Possible release of vasodilating agents from platelets is discussed. It is suggested that erythrocytic vasoconstrictive effect may be due to both hemoglobin and erythrocyte membrane proteins. Prostacyclin, nifedipine, and their combinations in particular, are shown to be capable of suppressing the vasoconstrictive effect of platelets and hemolysate, while physiologic vasoconstrictive activity was increased in patients with essential hypertension.
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PMID:[Effect of suspensions of human thrombocytes and erythrocytes on the tonus of a perfused carotid artery in the cat]. 341 67


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