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

It is known that endothelin-1 stimulates the release of nitric oxide and prostaglandins in various vascular beds. We designed the present study to analyze the roles of prostaglandins and nitric oxide in the effect of endothelin-1 on the regulation of renal hemodynamics and renin release. We used N omega-nitro-L-arginine methyl ester (L-NAME) and meclofenamic acid to inhibit the production of nitric oxide and prostaglandins, respectively. With a nonfiltering kidney model, renal blood flow was reduced 21% in dogs treated with L-NAME and 18% in dogs treated with meclofenamic acid. Inhibition of nitric oxide and prostaglandins, however, produced opposite effects on estimated glomerular hydraulic pressure: L-NAME increased glomerular hydraulic pressure from 63.1 +/- 0.9 to 64.6 +/- 1.3 mm Hg (P < .01), and meclofenamic acid reduced glomerular hydraulic pressure from 63.3 +/- 1.4 to 59.8 +/- 1.6 mm Hg (P < .01). Endothelin-1 infusion produced a dose-dependent reduction in renal blood flow after blockade of nitric oxide and prostaglandins. The responses of glomerular hydraulic pressure were different in the two groups during endothelin-1 infusion. Endothelin-1 progressively reduced glomerular hydraulic pressure in a dose-dependent fashion in the meclofenamic acid group. However, endothelin-1 slightly increased glomerular hydraulic pressure until the infusion rate reached 5.0 ng/kg per minute. At that rate, endothelin-1 reduced glomerular hydraulic pressure from 63.3 +/- 1.4 to 47.0 +/- 1.4 mm Hg in the meclofenamic acid group (P < .01), a more than 25% reduction, whereas at the same dose, endothelin-1 reduced glomerular hydraulic pressure only less than 2% in the L-NAME group. In addition, blockade of nitric oxide and prostaglandins did not alter the inhibitory effect of endothelin-1 on renin release in the non-filtering kidney. Therefore, the present study demonstrates that the release of nitric oxide and prostaglandins might modulate the effects of endothelin-1 on the renal circulation. The present findings suggest that the differential vasoconstrictive effects of endothelin-1 on preglomerular and postglomerular vessels are associated with its stimulation of nitric oxide and prostaglandin production.
Hypertension 1996 Sep
PMID:Roles of prostaglandins and nitric oxide in the effect of endothelin-1 on renal hemodynamics. 879 19

The vascular endothelium regulates the tone of the underlying smooth muscle and the reactivity of blood elements such as platelets and neutrophils by the release of mediators, in particular nitric oxide, prostacyclin and endothelin-1. The first two of these are potent vasodilators which also inhibit platelet and neutrophil aggregation and adhesion, while endothelin-1 is the most potent mammalian vasoconstrictor peptite yet found. There are also interactions between these mediators. For instance, endothelin-1 acts on specific receptors on the endothelium to increase the release of nitric oxide and prostacyclin, while nitric oxide depresses the production and/or release of endothelin-1 from endothelial cells. Endothelin-1 and prostacyclin do not appear to be involved in the basal regulation of blood pressure whereas nitric oxide does for inhibition of its production in normotensive animals produces a marked elevation in blood pressure. Conversely, numerous vascular disease states have been associated with elevations in the production and/or release of endothelin-1 and it has been implicated in the deleterious changes associated with ischaemia/reperfusion injury, subarachnoid haemorrhage and hypertension. Endothelin-1 has also been proposed to be pro-atherogenic, as have reductions in the production of the vasodilator mediators nitric oxide and prostacyclin.
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PMID:Influence of endothelial mediators on the vascular smooth muscle and circulating platelets and blood cells. 880 31

Persistent hypertension after nephrectomy is in most cases due to increased fluid volume. Endothelin-1 is a potent endogenous vasoconstrictor peptide. Its role in the development and maintenance of hypertension is not completely understood, but it might be significant in some cases. We report a case of stage IV hypertension after nephrectomy with elevated endothelin-1 levels and no volume overload.
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PMID:Elevated endothelin-1 levels and persistent stage IV hypertension in a nonvolume overloaded anephric patient. 923 39

Endothelin-1 (ET-1) has been implicated in the regulation of vascular tone in various pathological conditions. To examine the effect of in vivo overexpression of the peptide in rats, we prepared recombinant adenovirus stocks encoding the human preproET-1 cDNA (Ad.ET-1) or Escherichia coli lacZ (Ad.betaGal), each driven by cytomegalovirus early promoter. Ad.ET-1 or Ad.betaGal was injected into the caudal vein of rats and the animals were studied under anesthesia 96 h later. Hepatic overexpression of the virus-derived human ET-1 mRNA was accompanied by a 13-fold elevation of liver ET-1 content in the Ad.ET-1 group. Circulating plasma ET-1 levels in the Ad.ET-1 group were sixfold higher than those in the Ad.betaGal group. Mean arterial blood pressure was increased by 28 mmHg in the Ad.ET-1 group as compared with the Ad.betaGal group. In the Ad.ET-1 group, intravenous infusion of the ET(A) receptor antagonist FR 139317 reduced the blood pressure to levels seen in the Ad.betaGal group, whereas the same antagonist did not significantly alter the blood pressure in the Ad.betaGal group. Intravenous infusion of the ET(B) receptor antagonist BQ-788 caused a small but significant increase in blood pressure in both groups. These findings demonstrate that endogenous overexpression of preproET-1, accompanied by an elevation of plasma ET-1 concentrations to the levels seen in pathophysiological states, can cause systemic hypertension through the activation of the ETA receptor.
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PMID:Systemic hypertension induced by hepatic overexpression of human preproendothelin-1 in rats. 894 55

Endothelin-1 (ET-1) is a potent vasoconstrictor released by vascular endothelium. Because endothelial cell damage is considered determinant in the pathophysiology of pregnancy-induced hypertension (PIH), this study was conducted to evaluate the role of ET-1 produced by feto-placental tissues in PIH. Amniotic fluid samples obtained by amniocentesis from patients with PIH (N = 33), intrauterine growth retardation (IUGR) (N = 16), and PIH associated with IUGR (N = 12) were evaluated for ET-1 and compared to 42 normotensive pregnancies using a specific radioimmunoassay. ET-1 levels were significantly increased in PIH (35.6 +/- 1.9 pg/ml) and IUGR groups (33.8 +/- 4.6 pg/ml) compared to controls (20.8 +/- 1.4 pg/ml) (P < 0.01). In patients with PIH associated with IUGR, ET-1 concentrations were higher (P < 0.05) with no correlation with the severity of IUGR. Our data indicate that in PIH and IUGR ET-1 production and/or secretion is enhanced in the amniotic compartment, suggesting that the peptide may contribute to the pathophysiologic modification observed in these conditions.
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PMID:Amniotic fluid endothelin-1 levels are increased in pregnancy-induced hypertension and intrauterine growth retardation. 895 2

Endothelin-1 (ET-1) is a 21-amino acid peptide that potently modulates renal function. ET-1 is produced by, and binds to, most renal cell types. ET-1 exerts a wide range of biologic effects in the kidney, including constriction of most renal vessels, mesangial cell contraction, inhibition of sodium and water reabsorption by the nephron, enhancement of glomerular cell proliferation, and stimulation of extracellular matrix accumulation. ET-1 functions primarily as an autocrine or paracrine factor; its renal effects must be viewed in the context of its local production and actions. This is particularly important when comparing ET-1 biology in the nephron, where it promotes relative hypotension through increased salt and water excretion, with ET-1 effects in the vasculature, where it promotes relative hypertension through vasoconstriction. Numerous studies indicate that ET-1 is involved in the pathogenesis of a broad spectrum of renal diseases. These include those characterized by excessive renal vascular resistance, such as ischemic renal failure, cyclosporine (CyA) nephrotoxicity, radiocontrast nephropathy, endotoxemia, rhabdomyolysis, acute liver rejection, and others. ET-1 appears to play a role in cell proliferation in the setting of inflammatory glomerulonephritides. The peptide also may mediate, at least in part, excessive extracellular matrix accumulation and fibrosis occurring in chronic renal failure, diabetes mellitus, and other disorders. Deranged ET-1 production in the nephron may cause inappropriate sodium and water retention, thereby contributing to the development and/or maintenance of hypertension. Finally, impaired renal clearance of ET-1 may cause hypertension in patients with end-stage renal disease. Many ET-1 antagonists have been developed; however, their clinical usefulness has not yet been determined. Despite this, these agents hold great promise for the treatment of renal diseases; it is hoped that the next decade will witness their introduction into clinical practice.
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PMID:Endothelins in the normal and diseased kidney. 900 26

We investigated the effects of endothelin-1 on nitric oxide synthesis in vascular smooth muscle cells. We measured the production of nitrite, a stable metabolite of nitric oxide, and the expression of inducible nitric oxide synthase mRNA and protein in cultured rat vascular smooth muscle cells. Incubation of the cultures with interleukin-1 beta (10 ng/mL) for 24 hours caused a significant increase in nitrite production. Endothelin-1 significantly decreased the interleukin-1 beta-induced nitrite production by vascular smooth muscle cells in a dose-dependent manner (10(-11) to 10(-8) mol/L). Incubation with interleukin-1 beta for 24 hours induced expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells, whereas endothelin-1 showed a suppressive effect on their expressions. Addition of the endothelin type A receptor antagonist BQ-485, but not the endothelin type B receptor antagonist BQ-788, dose-dependently inhibited the effect of endothelin-1. After protein kinase C activity was functionally depleted by treatment of cells with phorbol 12-myristate 13-acetate for 24 hours, the effect of endothelin-1 was abolished. These results indicate that endothelin-1 acts on endothelin type A receptors and inhibits nitric oxide synthesis in interleukin-1 beta-stimulated vascular smooth muscle cells at least partially through a protein kinase C-dependent pathway.
Hypertension 1997 Jan
PMID:Endothelin-1 inhibits nitric oxide synthesis in vascular smooth muscle cells. 903 82

To investigate the involvement of endogenous opioids in acute increases in blood pressure and their functional relationship with atrial natriuretic factor and endothelin-1, we assessed plasma levels of beta-endorphin, met-enkephalin, dynorphin B, catecholamines, atrial natriuretic factor, and endothelin-1 before and after administration of the opioid antagonist naloxone hydrochloride (8 mg i.v.) in 28 hypertensive patients with a stress-induced acute increase in blood pressure. Ten patients with established mild or moderate essential hypertension and 10 normotensive subjects served as control groups. Opioids, atrial natriuretic factor, and endothelin-I were radioimmunoassayed after chromatographic preextraction; catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Patients with an acute increase in blood pressure (systolic, 203.2 +/- 2.2 mm Hg; diastolic, 108.4 +/- 1.3) had plasma opioid, catecholamine, and atrial natriuretic factor levels significantly (P < .01) higher than hypertensive control patients (systolic pressure, 176.4 +/- 1.0 mm Hg; diastolic, 100.0 +/- 1.4), who had a hormonal pattern similar to that of normotensive subjects (systolic pressure, 123.2 +/- 1.5 mm Hg; diastolic, 75.0 +/- 2.0). Endothelin-1 did not differ in any group. In patients with an acute increase in blood pressure, naloxone significantly (P < .01) reduced blood pressure, heart rate, opioids, catecholamines, and atrial natriuretic factor 10 minutes after administration. Naloxone effects on blood pressure, heart rate, opioids, and catecholamines wore off within 20 minutes. In control groups, naloxone failed to modify any of the considered parameters. Our findings suggest that pressor effects of opioid peptides mediated by the autonomic nervous system during stress-induced acute episodes of blood pressure increase in hypertensive patients.
Hypertension 1997 Jan
PMID:Pressor effects of endogenous opioid system during acute episodes of blood pressure increases in hypertensive patients. 903 88

Endothelin-1 (ET-1), which is secreted from vascular endothelial cells, is not only a potent vasoconstrictor but also a vascular smooth muscle cell growth factor. The direct effect of ET-1 on vascular smooth muscle cells, mediated via its specific receptor may therefore play an important role in hypertension and atherosclerosis. Our previous studies indicated that ET-1 secretion from cultured aortic endothelial cells from spontaneously hypertensive rats (SHRs) at the prehypertensive stage (4 weeks old) was not significantly different from that of cells from age-matched Wistar-Kyoto (WKY) rats. In this study, the binding of ET-1 to cultured aortic smooth muscle cells from SHRs and WKY rats was studied. Using tissue explant techniques, rat aortic smooth muscle cells from SHRs and age-matched WKY rats of different ages (4 and 24 weeks old) were successfully cultured in vitro. The maximum binding capacity (Bmax) and binding affinity (Kd) of ET-1 to cultured aortic smooth muscle cells were evaluated by a receptor-binding assay. The data revealed that the affinity of ET-1 binding to smooth muscle cells was similar in all 4 groups of experimental rats. However, the Bmax of cultured smooth muscle cells from 24-week-old SHRs was 2.5 times higher than of smooth muscle cells from age-matched WKY rats (8.64 +/- 0.72 vs 3.69 +/- 0.10 fmol/10(6) cells) and 1.5 times higher than in aortic smooth muscle cells from 4-week-old SHRs (8.64 +/- 0.72 vs 5.36 +/- 0.36 fmol/10(6) cells). These results suggest that hypertension in SHRs may be related to a high density of ET-1 receptors on arterial smooth muscle cells.
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PMID:Comparison of endothelin binding sites in cultured aortic smooth muscle cells from spontaneously hypertensive and normotensive rats. 907 Sep 70

1. Depressor and pressor effects of endothelin-1, -2 and -3 in relation to hypertension were investigated in conscious WKY and SHRSP. 2. Changes of systolic arterial pressure to both depressor and pressor responses caused by three doses of endothelin-1, -2 or -3 (0.1, 0.3 and 1 nmol/kg) occurred to a similar extent between WKY and SHRSP. These data showed that endothelins may not exert an important role on the pathogenesis of hypertension. 3. Endothelin-1 decreased the cardiac index more in SHRSP than in WKY, indicating the dominance of ETA receptors in SHRSP compared with WKY. 4. ET-1 was the most potent vasodepressor and vasodilator of three endothelin peptides in rats. 5. During the pressor responses to endothelin-1 and -3, cardiac arrhythmia was observed with high frequency in the animals of both groups, indicating the arrhythmogenic effect of ET.
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PMID:Comparative haemodynamic studies of endothelin-1, -2 and -3 on conscious SHRSP and WKY. 907 54


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