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

ENDOTHELIUM-DERIVED NITRIC OXIDE: The endothelium is a source of vasoactive factors among which the most relevant are nitric oxide and endothelin. Nitric oxide is synthesized from L-arginine by a family of nitric oxide synthases and is a widespread biological mediator. It is implicated in many physiological and pathophysiological processes, including a variety of cardiovascular diseases like hypertension. NITRIC OXIDE AND HYPERTENSION: The release of nitric oxide seems to be modulated by changes in blood pressure. However, the role of nitric oxide in hypertension is still controversial and seems to vary depending on the stage of the disease and the model studied. In spontaneous hypertension, the production of nitric oxide is increased but inefficacious, probably because of increased inactivation or scavenging. In the heart the production of nitric oxide seems to be increased, probably as a compensatory mechanism against hypertension. In salt-induced hypertension, nitric oxide production may be impaired. In human hypertension, pharmacological experiments reveal an impaired nitric oxide dilator mechanism. In pulmonary hypertension, the use of nitric oxide gas inhalation has been proposed as a future therapy for this condition. ENDOTHELIN: Endothelin-1 is a potent vasoconstrictor peptide produced and released from endothelial cells. In isolated blood vessels, endothelin causes profound contraction. The hemodynamic effects of endothelin can be explained by the activation of two endothelin receptors, ETA and ETB. The relationship between endothelin and hypertension is not clear. Although plasma endothelin levels are normal in most patients with essential hypertension, the hypertensive blood vessel wall may contract more profoundly in response to the peptide; hence, endothelin antagonists may have antihypertensive effects in patients with hypertension.
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PMID:Endothelium-derived vasoactive factors in hypertension: nitric oxide and endothelin. 857 87

Endothelin-1 (ET-1) is a potent vasoconstrictor and inotropic agent which may also induce cell hypertrophy. The role of ET-1 in ventricular hypertrophy in hypertension is unknown. We investigated ET-1 gene expression and immunoreactive ET-1 (ir-ET-1) concentration in the heart of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. To identify the cellular sites of ET-1 production in the heart, we performed in situ hybridization histochemistry. DOCA-treated rats which underwent unilateral nephrectomy (Uni-Nx) or not, exhibited mild systolic blood pressure elevation and ventricular hypertrophy. Blood pressure elevation and cardiac hypertrophy were more severe in DOCA-salt hypertensive rats. Ventricular ET-1 mRNA was similar in Uni-Nx control and DOCA-treated rats by Northern blot analysis, whereas in DOCA-salt hypertensive rats it was significantly increased. Ir-ET-1 concentration was also enhanced in ventricles from DOCA-salt hypertensive rats compared with Uni-Nx control rats. In situ hybridization histochemistry using a 35S-labelled complementary RNA ET-1 probe demonstrated that the level of ET-1 mRNA transcripts was increased exclusively in endothelial cells of large epicardial and small intramyocardial coronary arteries and in areas of the endocardium, but not significantly in myocardial cells of either the atria or ventricles. Enhanced ET-1 production may contribute to vascular changes, both structural and functional, in the heart in this model of hypertension in the rat, but probably does not contribute to the severe cardiac hypertrophy found in DOCA-salt hypertensive rats.
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PMID:Increased endothelin-1 gene expression in the endothelium of coronary arteries and endocardium in the DOCA-salt hypertensive rat. 857 29

Endothelin-1 (ET-1), a newly discovered peptide with potent vasoconstrictor and growth-promoting effects, has been implicated in high blood pressure and cardiac hypertrophy in the spontaneously hypertensive rat (SHR). In the present study, we measured plasma ET-1 levels and tissue ET-1 concentrations in the four cardiac chambers of 17- to 18-week-old SHR and their normotensive controls. Wistar Kyoto (WKY) rats. SHR had slightly but significantly higher plasma ET-1 levels than WKY. The ventricles had the highest ET-1 content and the atria in both strains had the highest ET-1 concentrations. ET receptor subtypes were analysed by radiogand binding with ET-1, BQ-123 and IRL 1620 in crude membrane preparations of the four cardiac chambers. No differences in receptor subtype densities or affinities were apparent between the two strains. ET(A) represented 75 to 85% of both ET receptors. Competition analysis revealed that in both strains left ventricular tissue had lower receptor densities and higher affinities than the atria. These results suggest that ET-1 and its receptor although contributing in the maintenance of high blood pressure may not be an important factor during stable cardiac hypertrophy in adult SHR. The differential distribution of ET-1 content and receptor densities favoring the atria in both strains suggest that this peptide may have a different physiological role in the atria from that in the ventricles.
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PMID:Cardiac endothelin-1 content and receptor subtype in spontaneously hypertensive rats. 857 47

Endothelin-1 (ET-1) influences vascular function by modulating intracellular free Ca2+ concentration ([Ca2+]i) in smooth muscle. This study investigated the effects of ET-1 on [Ca2+]i and contractile responses in resistance vessels of young prehypertensive (5 week) and adult hypertensive (17 week) spontaneously hypertensive rats (SHRs) and in age-matched normotensive Wistar-Kyoto (WKY) rats. Third-order branches of mesenteric arteries were mounted in a perfusion myograph and maintained at 60 mm Hg. Vessel [Ca2+]i was measured by Fura-2 and contraction was determined using video imaging to record lumen diameter. [Ca2+]i was higher (p < 0.01) in 5- and 17-week SHRs compared with 5- and 17-week WKYs rats. ET-1 increased [Ca2+]i and contractile responses in a dose-dependent manner in all groups. ET-induced [Ca2+]i change and vessel contractility were not significantly different between age-matched SHR and WKY groups, but [Ca2+]i responses were more sensitive in 5- compared with 17-week SHRs. These data demonstrate that ET-1-stimulated [Ca2+]i and contractile responses in resistance arteries are similar in age-matched WKY rats and SHRs and are blunted in adult SHRs compared with young prehypertensive rats. Therefore, ET-1 may not play a major role in the development of hypertension in SHRs.
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PMID:Ca2+ and contractile responses of resistance vessels of WKY rats and SHR to endothelin-1. 858 60

Endothelin-1 (ET-1) has been implicated in atherosclerosis, hypertension, and restenosis, all of which involve abnormal vascular smooth muscle cell function and/or proliferation. We have previously established that human umbilical vein smooth-muscle cells (HUVSMCs) can secrete ET, (1) whereas A10 cells do not. Therefore, we investigated the effect of exogenously added ET-1 on receptor density (Bmax) of A10 cells. Compared to controls, A10s exposed to ET-1 for 48 h showed a significant decrease (79%) in receptor density, with no change in affinity. In contrast, incubation of A10s with the ETA-selective antagonist FR139317 (at a concentration blocking 99% of ET receptors) for 48 h caused a significant increase (245%) in Bmax and a significant decrease in affinity. These changes persisted after coincubation with both ET-1 and FR139317, indicating that the antagonist was able to block the effects of exogenous ET-1. In concordance, incubation of HUVSMCs with FR139317 for 24 h caused a significant increase in receptor density (> 1,000%), although there was no change in levels of immunoreactive (IR) ET or big ET-1. However, after a shorter incubation (1 h), there was no change in Bmax but IR ET was significantly elevated by 878%, whereas IR big ET-1 was depressed by 86% compared to controls. Incubation of HUVSMCs with FR139317 did not affect receptor affinity. Our observations suggest that whereas the application of exogenous ET to A10s causes downregulation of ET receptor expression, the ETA antagonist FR139317 causes upregulation of ET receptor expression in VSMCs regardless of their ability to secrete ET. In VSMCs capable of secreting ET, acute antagonism of the ETA receptor causes a significant increase in IR-ET and a decrease of IR-big ET-1 levels.
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PMID:Regulation of endothelin receptor expression in vascular smooth-muscle cells. 858 11

Endothelin-1 (ET-1) has hypertrophic and mitogenic properties. Enhanced ET-1 gene expression in blood vessels of deoxycorticosterone acetate (DOCA)/salt hypertensive rats and DOCA/salt spontaneously hypertensive rats (SHRs) was previously demonstrated. In this study, the effect on ET-1 gene expression in blood vessels and on vascular hypertrophy of the development of hypertension of DOCA/salt hypertensive rats, and that of salt and DOCA, were investigated in Sprague-Dawley rats and in SHRs. Increased abundance of ET-1 mRNA and a greater content of immunoreactive ET-1 were found with progression of hypertension in the aorta and the mesenteric arterial bed only in DOCA/salt hypertensive rats and in DOCA/salt SHRs. Vascular expression of ET-1 was not enhanced in DOCA- or salt-treated rats, even when blood pressure rose to a mean systolic pressure of 210 mm Hg. The media thickness and the media cross-sectional area of mesenteric resistance arteries of all groups of rats, including SHRs and Wistar-Kyoto (WKY) rats, exhibited a close correlation with systolic blood pressure. In DOCA/salt hypertensive rats after 5 weeks and in DOCA/salt SHRs in which significant over-expression of ET-1 was present in blood vessels, vascular morphometric parameters were excessive for the level of systolic blood pressure. In DOCA/salt hypertensive rats and DOCA/salt SHRs treated with the combined ETA/ETB endothelin receptor antagonist bosentan, vascular morphometry correlated more closely with blood pressure, even though the blood pressure was only slightly lower than that of untreated rats. Lumen diameter correlated with blood pressure in all groups, including those overexpressing ET-1. These data support the hypothesis that ET-1 gene overexpression in blood vessels may accentuate vascular hypertrophy, but not remodeling, in DOCA/salt hypertensive rats and DOCA/salt SHRs in excess of that caused by blood pressure elevation per se.
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PMID:Enhanced expression of endothelin-1 gene may cause blood pressure-independent vascular hypertrophy. 858 58

Mesangial cell growth and accumulation of extracellular matrix proteins constitute key features of progressive glomerular injury. Endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictor agents, evoke a number of similar responses in mesangial cells. In rat mesangial cells, we compared ET-1 and Ang II effects on matrix protein production and cell proliferation as well as the potential interaction between the two hormones. When cells in 0.5% fetal calf serum were incubated for 24 hours with various concentrations of ET-1 or Ang II, both peptides stimulated, in a dose-dependent manner, fibronectin and type IV collagen mRNA expression, fibronectin synthesis, and mitogenesis. Incubation with specific receptor antagonists of both hormones demonstrated that endothelin subtype A (ETA) and angiotensin type 1 (AT1) receptors were involved. Preincubation of cells with two different protein kinase C inhibitors or with a neutralizing anti-transforming growth factor-beta antibody, but not an unrelated IgG, diminished the peptide-induced fibronectin synthesis. A dual interrelation seems to exist between ET-1 and Ang II. Thus, the AT1 receptor antagonist losartan and the angiotensin-converting enzyme inhibitors quinaprilat and captopril diminished the ET-1-mediated effects, whereas, the ETA receptor antagonist BQ-123 diminished the Ang II-induced fibronectin synthesis and mesangial cell proliferation. Our results suggest that ET-1 and Ang II stimulate matrix protein synthesis and mesangial cell mitogenesis through ETA and AT1 receptors, respectively, by complicated mechanisms, implicating protein kinase C activation, synthesis of transforming growth factor-beta, and release of one peptide by the other. These data could be important for a better understanding of the participation of vasoactive substances in the pathogenesis of glomerulosclerosis.
Hypertension 1996 Apr
PMID:Effects and interactions of endothelin-1 and angiotensin II on matrix protein expression and synthesis and mesangial cell growth. 861 64

Endothelin-1 (ET-1) exerts powerful vasoconstrictive and blood pressure elevating properties through endothelial cells. However, no systematic examination of ET-1 in migraine has ever been attempted. The present investigation was focused on evaluating the level of ET-1 in patients with migraine with aura. Studies on ET-1 were made in 17 patients with migraine with aura (age, 23.4 +/- 9.1 years old, mean +/- SD) according to the Classification of Headache of the Ad Hoc Committee. All patients had been free of migraine attacks for at least 7 days prior to the examination. Twenty-eight age-matched healthy volunteers (age, 23.0 +/- 12.3 years old) were similarly used as a control group. None of them revealed evidence of any other disease, such as hypertension, obesity, or heart disease. Informed consent was obtained from each subject. We measured the immunoreactive ET-1 in plasma by radioimmunoassay. The plasma level of ET-1 in migraine was 2.53 +/- 1.06 pg/ml. On the other hand, the level of ET-1 in the controls was 4.24 +/- 0.80 pg/ml. The ET-1 level in migraine was significantly lower than that in the controls (p < 0.002). We also measured the level of ET-1 in the cerebrospinal fluid (CSF). There was no significant difference between migraine (23.2 +/- 3.10 pg/ml) and the control group (20.85 +/- 3.20 pg/ml). In conclusion, the lower plasma level of ET-1 observed in the patients with migraine is consistent with the pathogenesis of migraine, further supporting the hypothesis that a lower ET-1 may be closely related to marked vasodilatation following constriction partly due to a deficiency of ET-1 for maintaining vasoconstriction.
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PMID:[Lower level of endothelin-1 in migraine with aura]. 872 Mar 38

The effects of the endothelin receptor antagonist TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-L-ala nyl-L-alpha-aspartyl-D-2-(2-thienyl)glycyl-L-leucyl-D-tryptophyl]+ ++disodiu m salt) and BQ-123 (cyclo[D-Asp-Pro-D-Val-Leu-D-Trp]) were studied in the rat heart to characterize the receptor subtypes responsible for the cardiovascular actions of endothelin-1. Endothelin-1 induced a transient decrease and subsequent increase in perfusion pressure in perfused rat hearts, and increased left ventricular developed pressure. TAK-044 diminished these endothelin-1-induced responses (100 pmol/heart) with IC50 values of 140, 57 and 1.3 nM, respectively. BQ-123 (1-30 mu M) partially inhibited the endothelin-1-induced hypertension (30-40%) in the rat heart, and failed to inhibit the hypotension. The positive inotropic effect of endothelin-1 was abolished by BQ-123. Neither indomethacin (10 mu M) nor Nomega-nitro-L-arginine methyl ester (100 mu M) attenuated the endothelin-1-induced hypotension. TAK-044 and BQ-123 attenuated the positive inotropic effect of endothelin-1 in rat papillary muscles. In rat cardiac membrane fractions, TAK-044 and BQ-123 inhibited [125I]endothelin-1 binding to endothelin ET(A) receptors with IC50 values of 0.39 +/- 0.6 and 36 +/- 9 nM, respectively, whereas only TAK-044 potently blocked the endothelin ET(B) receptor subtype (IC50 value: 370 +/- 180 nM). These results suggest that endothelin-1 modulates cardiovascular functions in the rat heart by activating both endothelin ET(A) and endothelin ET(B) receptors, all of which are sensitive to TAK-044.
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PMID:Pharmacological characterization of cardiovascular responses induced by endothelin-1 in the perfused rat heart. 872 Apr 78

Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictive peptide. In this study the Authors measured in 25 subjects (15 with essential hypertension and 10 normal) plasma levels of endothelin-1. Patients with hypertension had significantly higher plasma ET-1 concentration than normal subjects (2.18 +/- 1.07 vs. 1.36 +/- 0.40 pg/ml, p < 0.02). Plasma arginine vasopressin, renin activity and aldosterone concentration did not show significant differences between hypertensive and normotensive subjects. These data suggest that ET-1 may be involved in the development or maintenance of hypertension.
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PMID:[Increased plasma levels of endothelin in patints with essential arterial hypertension]. 876 80


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