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

Total inositol phosphate (IP) formation was measured in the aorta and femoral artery from rabbits at 1, 2, and 6 weeks after kidney wrapping, at which times the mean arterial pressures were 88 +/- 4, 96 +/- 3 and 126 +/- 7 (control = 74 +/- 3) mmHg. Noradrenaline (10(-7)-10(-4) M)-stimulated IP formation was increased in the aorta and femoral artery from hypertensive rabbits at 2 weeks (e.g., aorta noradrenaline 10(-6) M sham = 105 +/- 14%, hypertensive = 164 +/- 20% of control). In contrast, endothelin-1-stimulated IP formation was unchanged at 2 weeks. Noradrenaline-stimulated IP formation was unchanged at 1 and 6 weeks. Basal IP formation was not significantly different in normotensive and hypertensive animals. In perinephritis hypertension, there is an alteration in phosphatidylinositol metabolism in arterial smooth muscle at the time when blood pressure is rising rapidly. This alteration may affect a specific phosphatidylinositol pool that is linked to the alpha-adrenoceptor but not to the endothelin-1 receptor.
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PMID:Noradrenaline and endothelin-stimulated inositol phosphate formation in arterial smooth muscle from rabbits with perinephritis hypertension. 179 9

Hypertension is associated with a hypersensitive response to the Ca2+ channel activator, Bay K 8644. We investigated the effect of the endothelin ETA receptor antagonist, BQ-123, on the contractions induced by Bay K 8644 in aorta from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. BQ-123 (1 microM) decreased the sensitivity to Bay K 8644 of aorta of SHR down to that of WKY. This observation is consistent with a role for endothelin in hypertension.
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PMID:The endothelin ETA receptor antagonist, BQ-123, normalizes the response of SHR aorta to Ca2+ channel activator. 751 2

We studied the relevance of the ventrolateral medulla for the cardiovascular and respiratory effects of endothelin-1 in urethane-anesthetized rats. Microinjection of endothelin-1 into the rostral ventrolateral medulla (RVLM) evoked pressor and bradycardic effects followed by sustained decreases in blood pressure, bradycardia, and respiratory depression. These effects were inhibited by endothelin-A receptor antagonists (BQ-123 and BQ-610) but not by endothelin-B antagonists. In the caudal ventrolateral medulla (CVLM) endothelin-1 decreased blood pressure, renal sympathetic nerve activity, respiratory frequency, and phrenic nerve activity, whereas heart rate increased. Pretreatment with BQ-123 in the CVLM increased respiratory frequency by 15 +/- 6 breaths per minute and prevented the effects of intra-CVLM administration of endothelin-1. In separate experiments, the intracisternal administration of endothelin-1 (20 pmol) to rats pretreated with saline in both RVLM and CVLM resulted in a hypotensive and bradycardic phase that was followed by hypertension (50 +/- 15 mm Hg), bradycardia, and 100% mortality. In a separate group, pretreatment with BQ-123 in the RVLM and CVLM completely inhibited the hypotensive phase and reduced by 83% the subsequent rise in blood pressure evoked by endothelin-1. Cardiorespiratory arrest was prevented in all the rats in this group. Selective endothelin receptor blockade in the RVLM attenuated the hypertensive period of intracisternal administration of endothelin-1 and prevented mortality by 33%, whereas in the CVLM the endothelin receptor antagonist inhibited the initial hypotension and reduced mortality by 25%. Our results support the concept that in the ventral medulla, endothelin-1 can modulate cardiovascular and respiratory function.
Hypertension 1995 Aug
PMID:Cardiovascular and respiratory effects of endothelin in the ventrolateral medulla of the normotensive rat. 763 33

The goal of our studies is to elucidate the role of atrial natrluretic peptide (ANP) and endothelin-1 (ET-1) and their receptor mechanisms in hypoxia-induced pulmonary hypertension and the control of pulmonary artery pressure in patients with pulmonary hypertension. Our experimental model is the male Sprague-Dawley rat subjected to normobaric hypoxia (10% O2, 1 atm) x 4 weeks or less. Our hypothesis is that ET-1 and ANP gene expression are enhanced by exposure to hypoxia and that the ET-1 and ANP so generated have causal and protective, respectively, effects on the development of hypoxia-induced pulmonary hypertension. Results from our studies demonstrated that ANP gene expression and ANP secretion in the heart, and the sensitivity to both endogenous and exogenous ANP in the pulmonary vasculature of hypoxia adapted rats are enhanced during hypoxic exposure. These data defined a role for ANP as a modulator hormone that protects against the development of acute hypoxic pulmonary vasoconstriction and chronic hypoxic pulmonary hypertension. Our studies also demonstrated that ET-1 and endothelin-A receptor (ET-AR) gene expression were selectively enhanced in the pulmonary vasculature by exposure to hypoxia, and that the ET-1 so generated is an important mediator in acute and chronic hypoxia-induced pulmonary hypertension. These results suggest that the intrapulmonary ET-1, acting on ET-AR receptors in the pulmonary vasculature mediates the hypoxia-induced pulmonary vasoconstriction and hypertension. In addition, our recent experiments have demonstrated that administration of BQ-123, a selective ET-AR antagonist, abolished the pulmonary vasoconstrictor response to acute (0-90 min) and chronic (2 weeks) hypoxia, further suggesting that ET-1 plays an important role in the pathogenesis of hypoxia-induced pulmonary hypertension in the rat. Results from our studies also indicate that selective ANP analogs and ET-AR antagonists may be clinically useful for the treatment of pulmonary hypertension.
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PMID:The role of atrial natriuretic peptide and endothelin in hypoxia induced pulmonary hypertension. 770 79

We studied the effects of the selective endothelin A receptor antagonist FR139317 and the combined endothelin A/endothelin B receptor antagonist bosentan in rat mesenteric arteries by using a video dimension analyzer. In endothelium-denuded arteries, increasing concentrations of endothelin-1 evoked a biphasic vasoconstriction. The first phase was observed at low concentrations (10(-16) to 10(-11) mol/L) of endothelin-1 and was relatively weak. However, the contractions characterizing the second phase, which occurred at higher concentrations (10(-10) to 3 x 10(-8) mol/L) of endothelin-1, were much stronger. FR139317 concentration-dependently shifted the second phase of the endothelin-1-induced contraction curve to the right without affecting the first phase. In contrast, bosentan inhibited both the first and the second phase. Even after the blockade of endothelin A receptor, increasing concentrations of the endothelin B receptor agonists endothelin-3 and sarafotoxin S6c still induced small contractions. Maximal contractions induced by single-bolus extraluminal application of endothelin-3 (10(-9) mol/L) or sarafotoxin S6c (3 x 10(-8) mol/L) were markedly more pronounced than responses induced by cumulative concentrations, suggesting endothelin B receptor downregulation upon repeated and sustained activation. The response induced by a single bolus of endothelin-3 (10(-9) mol/L) was antagonized by bosentan but not by FR139317, confirming that endothelin B receptors were involved. In endothelium-intact arteries half-maximally precontracted with norepinephrine, bosentan but not FR139317 inhibited the relaxations induced by intraluminally applied endothelin-3. (ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Endothelin receptor subtypes in small arteries. Studies with FR139317 and bosentan. 772 25

Hypertension in the spontaneously hypertensive rat (SHR) is associated with reduced renal excretory function, low renal plasma flow, reduced glomerular filtration rate, and reduced renal interstitial hydrostatic pressure. The mechanisms responsible for these abnormalities in renal function are unknown. The purpose of this study was to determine the role of intrarenal endothelin in altering renal hemodynamic and excretory function in the SHR. Both PD 145065 (an endothelin A and B receptor antagonist) and FR 139317 (a selective endothelin A receptor antagonist) or saline was infused into the renal interstitium of 14- to 16-week-old SHR (n = 7) and age-matched Wistar-Kyoto rats (WKY) (n = 7). Renal perfusion pressure in some SHR was reduced to that of the WKY by a servocontrol system. At a renal perfusion pressure of 124 +/- 4 mm Hg, infusion of PD 145065. (0.03 mg.kg-1.min-1) and FR 139317 (0.02 mg.kg-1.min-1) significantly increased glomerular filtration rate (delta 22%), renal plasma flow (delta 37%), and renal interstitial hydrostatic pressure (from 3.2 +/- 0.5 to 5.4 +/- 0.6 mm Hg) in the SHR. These changes were associated with significant increases in urine flow, absolute sodium excretion, and fractional excretion of sodium. Similar improvements in renal plasma flow, renal interstitial hydrostatic pressure, and renal excretory function were obtained in the SHR whose renal perfusion pressure was not reduced (n = 7). Renal interstitial infusion of endothelin receptor antagonists had no effect on renal hemodynamic or excretory function in the WKY. These data demonstrate that endothelin receptor blockade within the kidney improves renal hemodynamic and excretory function in the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Endothelin antagonists improve renal function in spontaneously hypertensive rats. 772 48

Endothelin is a potent pressor agent mediated primarily through activation of endothelin-A receptors on vascular smooth muscle. Surprisingly, there is no consensus in the literature regarding the role of endothelin itself or endothelin-A receptors in hypertension. The goal of this study was to compare the effects of the novel, selective endothelin-A receptor antagonist BMS-182874 in various models of hypertension. BMS-182874 specifically inhibited the pressor response to endothelin-1 (0.3 nmol/kg IV) in Sprague-Dawley rats in a dose-dependent manner (ED25 = 8 mumol/kg IV) but had no effect on changes in mean arterial pressure brought about by other vasoactive agents. The antihypertensive effects of BMS-182874 were evaluated in conscious deoxycorticosterone acetate (DOCA)--salt hypertensive rats, spontaneously hypertensive rats (SHR), and sodium-deplete SHR. BMS-182874 reduced blood pressure in DOCA--salt hypertensive rats when administered at a dose of 30, 100, or 300 mumol/kg IV. A maximal decrease of approximately 45 mm Hg was observed after treatment with 100 mumol/kg IV. Three days of oral or intravenous treatment with BMS-182874 (100 mumol/kg) elicited a sustained decrease in blood pressure in the DOCA--salt hypertensive rats. In SHR, BMS-182874 decreased blood pressure by approximately 30 mm Hg, but the antihypertensive effects were similar at doses of 75, 150, and 450 mumol/kg PO. In sodium-deplete SHR, BMS-182874 did not significantly reduce blood pressure. In summary, BMS-182874 is a specific, orally active endothelin-A receptor antagonist that is efficacious in mineralocorticoid hypertension in rats but has less effect in sodium-replete and sodium-deplete SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Jun
PMID:Antihypertensive effects of a novel endothelin-A receptor antagonist in rats. 776 62

We determined the antihypertensive effects of BQ-123 (cyclo(D-Trp-D-Asp-L-Pro-D-Val-L-Leu-), sodium salt), a selective endothelin ETA receptor antagonist, in spontaneously hypertensive rats treated with deoxycorticosterone acetate-salt (DOCA-salt SHR). BQ-123 (1-30 mg/kg/h) decreased blood pressure in DOCA-salt SHR in a dose-dependent manner, although plasma immunoreactive endothelin-1 did not significantly increase and the maximal contractile response to endothelin-1 in the aorta significantly decreased as compared with values observed in age-matched SHR. These results suggest that endogenous endothelin-1 is involved in the maintenance of hypertension in DOCA-salt SHR, and that circulating endothelin-1 is not sufficient to reflect the physiological role of endothelin-1.
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PMID:Antihypertensive effects of BQ-123, a selective endothelin ETA receptor antagonist, in spontaneously hypertensive rats treated with DOCA-salt. 798 65

Endothelin-1 is a potent vasoconstrictor produced by vascular endothelial cells. A recently cloned endothelin-1-selective receptor, the endothelin-A receptor, mediates the vasoconstrictive action of endothelin-1. Because endothelin-1 also possesses mitogenic properties, it may play a role in regulating the proliferation of intimal smooth muscle cells. In this study, we analyzed the expression of endothelin-A receptor gene in the thickened arterial intima of patients with hypertension. Internal mammary artery specimens obtained from 12 patients undergoing cardiovascular surgery were subjected to in situ hybridization using a digoxigenin-labeled cRNA probe. High, homogeneous signals of endothelin-A receptor mRNA were observed in the medial smooth muscle cells of all vessels examined but not in the endothelial cells. Patients with hypertension displayed more severe intimal thickening than those without hypertension. Immunohistochemical analysis suggested that almost all of the intimal proliferative cells originated from smooth muscle cells. In contrast to media, endothelin-A receptor mRNA signals in intimal smooth muscle cells were low and heterogeneous. In the thickened arterial intima of hypertensive patients, the signals were detected just beneath the luminal endothelium but not deep in the intimal smooth muscle cell layer. By contrast, staining with anti-alpha-smooth muscle actin antibody was more intense in the deep layer than in the subendothelium. These findings suggest that the modulation of endothelin-A receptor gene expression in smooth muscle cells differs between the intima and media. Its regulated expression in intimal smooth muscle cells might affect the proliferative activity of these cells in patients with hypertension.
Hypertension 1994 Mar
PMID:Endothelin-1-selective receptor in the arterial intima of patients with hypertension. 812 52

The current study was undertaken to define a biological role for the endothelin-A receptor in a clinically relevant model of altered systemic and renal function produced by suprarenal aortic cross-clamping. This model is associated with profound systemic and renal vasoconstriction, acute renal failure, and a significant increase in circulating endothelin. Studies were performed in three groups of anesthetized mongrel dogs. Group 1 (n = 5) underwent aortic cross-clamping for 1 hour; group 2 (n = 5) underwent aortic cross-clamping for 1 hour in the presence of BQ-123, a specific antagonist of the endothelin-A receptor; group 3 (n = 4) received BQ-123 alone. The marked systemic and renal vasoconstriction associated with aortic cross-clamping in group 1 was markedly attenuated in group 2 in the presence of BQ-123. Unlike the vasoconstrictor response, BQ-123 did not attenuate the decrease in glomerular filtration rate associated with this model. Under unstimulated conditions in group 3, BQ-123 had no actions on systemic or renal hemodynamics. In conclusion, the current study demonstrates that the systemic and renal vasoconstriction associated with aortic cross-clamping are in part mediated through the interaction of endothelin and the endothelin-A receptor. This study demonstrates the functional importance of increased endogenous endothelin in the regulation of vascular tone in this pathophysiological state.
Hypertension 1993 Jul
PMID:Biological role for the endothelin-A receptor in aortic cross-clamping. 831 93


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