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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to determine whether ischemia/reperfusion (I/R) injury in rat liver results in alterations in endothelin receptor expression. Hepatic ischemia was produced in rats for 60 min followed by 6 or 24 h reperfusion. Portal inflow pressure was increased (7.38+/-0.60 mmHg) at 24 hours after reperfusion. Serum ALT increased significantly at both 6 and 24 h (6 h; 258.3+/-74.3, 24 h; 243.1+/-74.8 IU/L). Portal vascular response to an endothelin-B receptor agonist (IRL 1620) was significantly increased in the I/R livers compared to control and this was potentiated by L-NAME. IRL 1620 also caused LDH release from I/R livers but not controls. LDH release after IRL 1620 in I/R livers correlated with increased portal pressure response. To determine whether the altered response might be the result of altered endothelin receptor expression, livers were harvested after reperfusion and total endothelin binding sites were determined by competitive binding with ET-1. Proportion of endothelin receptor subtypes (ET(A)/ET(B)) was determined using the ET(A) antagonist BQ-610 (1 microM) and ET(B) agonist IRL-1620 (100 nM). There were no significant changes in Kd but Bmax for endothelin-1 was decreased in I/R group especially non-ischemic lobe at 24 h. ET(A) receptors were significantly decreased whereas ET(B) receptors were increased. These changes were more pronounced at 24 h after reperfusion than at 6 h. Interestingly, the changes in ET receptors was observed identically both in ischemic and non-ischemic lobes (ischemic lobe ET(A) 41.9%, ET(B) 51%; non-ischemic lobe ET(A) 38.8%, ET(B) 49.5%). These results indicate that the major functional endothelin receptor subtype upregulated in I/R is the ET(B) receptor and that this upregulation may contribute to microvascular dysregulation and hepatic injury.
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PMID:Altered endothelin receptor subtype expression in hepatic injury after ischemia/reperfusion. 1063 73

The role of the endothelin-B receptor (ET(B)) in vascular homeostasis is controversial because the receptor has both pressor and depressor effects in vivo. Spotting lethal (sl) rats carry a naturally occurring deletion in the ET(B) gene that completely abrogates functional receptor expression. Rats homozygous for this mutation die shortly after birth due to congenital distal intestinal aganglionosis. Genetic rescue of ET(B)(sl/sl) rats from this developmental defect using a dopamine--hydroxylase (DBH)-ET(B) transgene results in ET(B)-deficient adult rats. On a sodium-deficient diet, DBH-ET(B);ET(B)(sl/sl) and DBH-ET(B);ET(B)(+/+) rats both exhibit a normal arterial blood pressure, but on a high-sodium diet, the former are severely hypertensive. We find no difference in plasma renin activity or plasma aldosterone concentration between salt-fed wild-type, DBH-ET(B);ET(B)(+/+) or DBH-ET(B);ET(B)(sl/sl) rats, and acute responses to intravenous L-NAME and indomethacin are similar between DBH-ET(B);ET(B)(sl/sl) and DBH-ET(B);ET(B)(+/+) rats. Irrespective of diet, DBH-ET(B);ET(B)(sl/sl) rats exhibit increased circulating ET-1, and, on a high-sodium diet, they show increased but incomplete hypotensive responses to acute treatment an ET(A)-antagonist. Normal pressure is restored in salt-fed DBH-ET(B);ET(B)(sl/sl) rats when the epithelial sodium channel is blocked with amiloride. We conclude that DBH-ET(B);ET(B)(sl/sl) rats are a novel single-locus genetic model of severe salt-sensitive hypertension. Our results suggest that DBH-ET(B);ET(B)(sl/sl) rats are hypertensive because they lack the normal tonic inhibition of the renal epithelial sodium channel.
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PMID:Salt-sensitive hypertension in endothelin-B receptor-deficient rats. 1074 72

Responses to human urotensin-II (hU-II) were investigated in human and rat pulmonary arteries. Rat pulmonary arteries: hU-II was a potent vasoconstrictor of main pulmonary arteries (2 - 3 mm i.d.) (pEC(50), 8.55+/-0.08, n=21) and was approximately 4 fold more potent than endothelin-1 [ET-1] (P<0.01), although its E(max) was considerably less (approximately 2.5 fold, P<0.001). The potency of hU-II increased 2.5 fold with endothelium removal (P<0.05) and after raising vascular tone with ET-1 (P<0.01). E(max) was enhanced approximately 1.5 fold in the presence of N(omega)-nitro-L-arginine methylester (L-NAME, 100 microM, P<0.01) and approximately 2 fold in vessels from pulmonary hypertensive rats exposed to 2 weeks chronic hypoxia (P<0.05). hU-II did not constrict smaller pulmonary arteries. Human pulmonary arteries ( approximately 250 microm i.d.): in the presence of L-NAME, 3 out of 10 vessels contracted to hU-II and this contraction was highly variable. hU-II is, therefore, a potent vasoconstrictor of rat main pulmonary arteries and this response is increased by endothelial factors, vascular tone and onset of pulmonary hypertension. Inhibition of nitric oxide synthase uncovers contractile responses to hU-II in human pulmonary arteries.
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PMID:Contractile responses to human urotensin-II in rat and human pulmonary arteries: effect of endothelial factors and chronic hypoxia in the rat. 1080 54

The role of endothelins (ET) in blood pressure elevation remains controversial. Data supporting involvement of the ET system in different forms of genetic and experimental hypertension in the rat has appeared in the literature in recent years. Production of endothelin (ET)-1 may be enhanced in several experimental rat models of hypertension. Examples of these exhibiting increased preproendothelin-1 mRNA or peptide in the vasculature include salt-sensitive forms like deoxycorticosterone (DOCA)-salt hypertension, DOCA-salt treated spontaneously hypertensive rat (SHR) and Dahl salt-sensitive rats, and other models like stroke-prone SHR, angiotensin II-infused rats and fructose-fed rats, and possibly 1-kidney 1 clip (1-K 1C) Goldblatt hypertensive rats. SHR, 2-kidney 1 clip (2-K 1C) Goldblatt hypertensive rats and chronic N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated hypertensive rats do not appear to exhibit an ET-1 component. Significant vascular growth, and a hypotensive response and regression of vascular growth after treatment with an ET antagonist demonstrate the endothelin-dependency present in some hypertensive models. Severity of high blood pressure elevation, salt-sensitivity and insulin resistance may be common denominators of involvement of the ET system in hypertension. ET antagonism in hypertension may result in regression of vascular damage, prevention of stroke and renal failure and improvement of heart failure. Whether the same is true in human hypertension remains to be established.
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PMID:Endothelin: role in experimental hypertension. 1097 78

The secretagogue effect of endothelins (ETs) on the rat adrenal cortex is mediated by the ETB receptor. ETB receptors are coupled with nitric oxide (NO) synthase (NOS), and NO is known to inhibit steroid-hormone secretion from adrenal cortex. We investigated whether ETB-mediated NO production interferes with the stimulatory action of ETs on rat adrenal cortex. The selective agonist of ETB receptor BQ-3020 concentration-dependently increased aldosterone secretion from dispersed zona glomerulosa (ZG) cells and corticosterone secretion from dispersed zona fasciculata-reticularis (ZF/R) cells, and the NOS inhibitor NG-nitro-L-arginine methylester (L-NAME) potentiated the effect of BQ-3020 in a concentration-dependent manner. The guanylate cyclase inhibitor Ly-83583, at a concentration suppressing guanylin- and L-arginine-induced cyclic-GMP release from dispersed adrenocortical cells, did not affect the secretory response of ZG and ZF/R cells to BQ-3020. ET-1, an agonist of both ETA and ETB receptors, stimulated the release of both aldosterone and corticosterone by in situ perfused rat adrenal gland. This effect was potentiated by L-NAME and unaffected by Ly-83583. Collectively, our findings allow us to suggest that endogenous NO exerts in vivo and in vitro a cyclic-GMP-independent buffering action on the ETB receptor-mediated adrenocortical secretagogue action of ETs.
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PMID:Buffering action of endogenous nitric oxide on the adrenocortical secretagogue effect of endothelins in the rat. 1111 9

We investigated the effects of the nitric oxide (NO) donor molsidomine and the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) on pulmonary endothelin (ET)-1 gene expression and ET-1 plasma levels in chronic hypoxic rats. Two and four weeks of hypoxia (10% O2) significantly increased right ventricular systolic pressure, the medial cross-sectional vascular wall area of the pulmonary arteries, and pulmonary ET-1 mRNA expression (2-fold and 3.2-fold, respectively). ET-1 plasma levels were elevated after 4 wk of hypoxia. In rats exposed to 4 wk of hypoxia, molsidomine (15 mg x kg(-1) x day(-1)) given either from the beginning or after 2 wk of hypoxia significantly reduced pulmonary hypertension, pulmonary vascular remodeling, pulmonary ET-1 gene expression, and ET-1 plasma levels. L-NAME administration (45 mg x kg(-1) x day(-1)) in rats subjected to 2 wk of hypoxia did not modify these parameters. Our findings suggest that in chronic hypoxic rats, exogenously administered NO acts in part by suppressing the formation of ET-1. In contrast, inhibition of endogenous NO production exerts only minor effects on the pulmonary circulation and pulmonary ET-1 synthesis in these animals.
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PMID:The NO donor molsidomine reduces endothelin-1 gene expression in chronic hypoxic rat lungs. 1115 4

There may be a relation between altered venous function, endothelin (ET)-1, and an impairment in the activity of endothelial-derived nitric oxide (NO) and prostanoids in salt-dependent hypertension. The present study examined the effects of salt intake on ET-induced changes in venomotor tone and the effects of blockade of NO synthase with N(G)-nitro-L-arginine methyl ester (L-NAME) and of cyclooxygenase with indomethacin on venomotor tone caused by the ET(B) selective agonist sarafotoxin 6c (S6c) in awake rats. Rats were anesthetized for permanent placement of catheters for measurements of arterial and venous pressures. A silicone balloon catheter was also fixed in the right atrium to produce brief circulatory arrest. Venomotor tone was estimated from measurements of mean circulatory filling pressure (MCFP) in conscious rats. There were no differences in mean arterial pressure, heart rate, or MCFP responses to short-term administration of ET-1 or S6c at different levels of salt intake. L-NAME or indomethacin did not change MCFP or the response of MCFP to short-term injection of S6c. In conclusion, neither basal MCFP nor integrated venomotor responses to short-term injection of ET-1 or S6c were altered by short-term changes in salt intake, blockade of NO synthase or cyclooxygenase. These data do not support the hypothesis that increased salt intake alters reactivity of veins to ET-1, NO, or prostanoids.
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PMID:Factors affecting endothelin-induced venous tone in conscious rats. 1121 1

We used novel digital contrasting methods to measure the effects of endothelin-1 (ET-1, 10(-6) to 10(-8) mol l(-1)), the nitric-oxide-releasing agent sodium nitroprusside (SNP, 10(-2) mol l(-1)) and N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10(-4) mol l(-1)), a non-selective inhibitor of nitric oxide synthase, on the diameter of tiny arteries and veins of the head in anaesthetized Xenopus laevis tadpoles (stage NF 50-53). Perfusion of the main artery and vein supplying the head with ET-1 caused an immediate, significant and dose-dependent vasoconstriction. While preincubation with L-NAME caused no significant change in vessel diameter, the constriction provoked by subsequent endothelin administration was significantly enhanced. Application of SNP caused a vasodilation that was significant only after preconstriction with ET-1 (10(-6) mol l(-1)). Our results provide strong evidence that the vasculature of developing Xenopus laevis tadpoles (NF stage 50-53) is influenced by endogenously released nitric oxide and endothelin. Vasoactive mediators released from vascular endothelial cells could be particularly important in vascular control in early embryos when the autonomic innervation is undifferentiated, poorly developed or even absent.
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PMID:Vascular control in larval Xenopus laevis: the role of endothelial-derived factors. 1182 88

The effect of contractions elicited with ET1 and AVP after preincubating rat aortic and tail artery rings with a hyperinsulinemic dose (3 nM) of insulin were studied. Insulin preincubation (120 min), in the presence of 0.1 mM L-NAME, depressed contraction of aortic rings to 0.01 microM ET1 (132 +/- 6 vs. 161 +/- 9 mg/mm2 in control, n = 25; p < 0.05) and to 1 microM AVP (84 +/- 7 vs. 110 +/- 9 mg/mm2 in control, n = 16; p < 0.05), but did not modify 45Ca influx to the cell. Insulin-induced relaxation was inhibited by indomethacin 10 microM, an antagonist of prostaglandin synthesis, and also by blockade of insulin receptors with 30 microM genistein. A short insulin preincubation (15 min) did not modify ET1 contractions. In rat tail artery, insulin preincubation (120 min) increased the force developed by ET1 (847 +/- 45 vs. 596 +/- 99 mgF/mgW in controls, n = 14) by stimulating TXA2 release and/or actions. In summary, the present results suggest that endothelial factors are involved in both the vasoconstrictor and vasodilator effects of insulin on rat vessels.
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PMID:Insulin preincubation effects on rat vessel contractile responses: role of the endothelium. 1182 79

Rat vascular smooth muscle cells (VSMC) were used to study the effect of 17beta -estradiol (E(2)) on cellular proliferation (cell counting), DNA synthesis ((3)H thymidine incorporation), MTT, c -fos mRNA expression and nitric oxide (NO) release. The results obtained showed that E(2) (10(-12) 10(-8) mol/L) induced NO release from VSMC in a concentration-dependent manner; 10(-8) mol/L E (2)significantly inhibited VSMC cellular proliferation and DNA synthesis induced by 10% FCS and 10(-7) mol/L ET-1, which was obviously reversed by 10(-7)mol/L tamoxifen and 10(-6) mol/L L-NAME; after a pretreatment for 24 hours, 10(-8)mol/L E(2) significantly inhibited VSMC c -fos mRNA expression induced by 10(-7)mol/L ET-1, which was also obviously reversed by 10(-6) mol/L L-NAME. These results suggest that the inhibitory effects of E(2) on VSMC cellular proliferation and c -fos mRNA expression are closely related with NO release in VSMC, which is, at least, partly medicated by ER.
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PMID:17beta-Estradiol inhibits vascular smooth muscle cell proliferation and c -fos expression: role of nitric oxide. 1193 Feb 35


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