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

Effect of endothelin (ET) on clonidine induced cardiovascular effects was studied in male Sprague-Dawley rats. Clonidine (75 micrograms/kg, iv) produced significant decrease in blood pressure and heart rate. ET-1 (50 ng/kg, iv) pretreatment completely antagonized the hypotension and bradycardia induced by clonidine. ET-2 (50 ng/kg, iv) and ET-3 (50 ng/kg, iv) had similar antagonistic effect on clonidine induced hypotension and bradycardia. The antagonistic effect of ET lasted for several hours, however, 4 hours after ET pretreatment only partial blockade of clonidine induced hypotension and bradycardia was observed. This indicated that the antagonistic effect of ET was reversible. Initial hypertensive response induced by high dose of clonidine (750 micrograms/kg, iv) could not be antagonized by ET-1, ET-2 or ET-3, while phenoxybenzamine, an alpha adrenoceptor antagonist, blocked the hypertensive response of clonidine. Thus, ET has no antagonistic effect on the initial hypertensive response but antagonizes the hypotensive and bradycardic effect induced by clonidine. Clonidine induced hypotension and bradycardia are mediated through central alpha 2 adrenoceptors while hypertension is mediated through peripheral alpha 2 adrenoceptors. It is concluded that central alpha 2 adrenoceptors are different from peripheral alpha 2 adrenoceptors and ET antagonizes the effect of clonidine only on central alpha 2 adrenoceptors but has no antagonistic activity on peripheral alpha 2 adrenoceptors.
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PMID:Evidence for antagonistic activity of endothelin for clonidine induced hypotension and bradycardia. 130 33

Endothelins (ET-1, ET-2 and ET-3) are a family of 21 amino acid peptides produced by endothelial cells. They are thought to regulate the local vasomotor tone with endothelium-derived relaxing factors. ETs are the most potent vasoconstrictor substances yet identified and veins and renal vasculature are the most sensitive targets. They reduce cardiac output and have positive inotropic and chronotropic effects. ETs increase the secretion of atrial natriuretic peptide (ANP), aldosterone and catecholamines but reduce renal blood flow and glomerular filtration and they also have mitogenic properties. ETs bind to receptors (ETA and ETB), activate phospholipase C, modulate intracellular Ca2+ concentration and open Ca2+ channels. Vasoactive agents (adrenaline, angiotensin, vasopressin, thrombin, endotoxins) and hypoxia stimulate the release of ET and also ET gene expression. Raised concentrations of plasma ET have been found to occur in several clinical conditions such as hypertension, myocardial infarction, cardiogenic shock, pregnancy induced hypertension, arteriosclerosis, Raynaud's disease, subarachnoid haemorrhage, uraemia, ulcerative colitis, Crohn's disease and surgical operations suggesting that ETs have a role in several patophysiological processes.
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PMID:Endothelin peptides: biological activities, cellular signalling and clinical significance. 138 14

Endothelin (ET) is a novel vasoactive peptide occurring in 3 isoforms (ET1, ET2, ET3) in humans. Derived from vascular endothelium cells, ET arises from a precursor peptide and exerts diverse actions through specific receptors. ET possess a wide spectrum of activities: a potent vasoconstrictor activity but also contraction of nonvascular smooth muscles (air-way, intestinal, urinary) or mitogenic actions, renal and endocrine effects. The physiological and/or physiopathological roles of endothelin is still unclear, but ET may play a part in the genesis of some vascular diseases as atherosclerosis, forms of hypertension or may be implicated in the pathogenesis of vasospasm.
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PMID:[Endothelin. A new class of vasoactive peptides]. 152 95

In order to gain insight into the potential role of endothelin, a 21 amino acid peptide produced by endothelial cells, in the development of complications of diabetes mellitus, basal plasma endothelin levels were measured in 152 patients with diabetes mellitus (83 patients with type 1 diabetes mellitus, 69 patients with type 2 diabetes mellitus) and compared to those in 50 healthy controls. Blood was drawn at 8:00 AM under resting conditions and endothelin was measured after prior extraction by a sensitive radioimmunoassay specific for both endothelin 1 and 2. Endothelin levels were increased in patients with diabetes mellitus in comparison to controls. In type 1 diabetes mellitus a positive correlation between endothelin levels and age was found. We found that 60% of patients with type 1 diabetes mellitus and elevated endothelin levels higher than 2.5 pg/mL (highest value in a control person) had had diabetes for more than 20 years (P less than .05 v patients with normal endothelin levels). In type 2 diabetes mellitus the relation between elevated endothelin levels and diabetes duration was reversed. Glycosylated hemoglobin (HbA1) concentrations above 10% of total hemoglobin were measured in 62% of the patients. Arterial hypertension was present in 60% of the patients with type 1 diabetes mellitus and increased endothelin levels greater than 2.5 pg/mL (both P less than .05 v patients with normal endothelin levels).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased plasma levels of endothelin in diabetic patients with hypertension. 157 42

The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 and/or -2(ET1 + 2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1 + 2 from cultured endothelial cells in a dose-dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1 + 2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol-induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome.
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PMID:Ethanol stimulates immunoreactive endothelin-1 and -2 release from cultured human umbilical vein endothelial cells. 159 May 57

The effect of endothelin (ET)-1 was investigated on resistance arteries of less than 300-microns lumen diameter from the mesenteric circulation, mounted on a wire myograph, in deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 wk of developing hypertension and in uninephrectomized controls. Arteries from DOCA-salt hypertensive rats presented a significantly reduced external and lumen diameter and increased media width and wall cross-sectional area. Vessels from DOCA-salt hypertensive rats responded to ET-1 with lower active wall tension and media stress. Because the lumen diameter was significantly decreased in DOCA-salt hypertensive rats, the active pressure developed in response to ET-1 was similar in both groups. In contrast, the maximal tension response to arginine vasopressin was enhanced in DOCA-salt hypertensive rats. The sensitivity to both peptides and norepinephrine (NE) was similar in both groups. After removal of endothelium by exposure to the nonionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, ET-1 elicited tension responses that were also lower in DOCA-salt hypertensive rats, whereas NE responses were similar in both groups. These results demonstrate significant morphological and functional changes in small arteries of DOCA-salt hypertensive rats within 2 wk of developing hypertension and blunted reactivity to ET-1. Because similar results were found after removal of endothelium, it is likely that neither prior receptor occupation by endogenous ET nor acute effects of other endothelial cell products play a role in the reduced responsiveness to ET of vascular smooth muscle of small resistance arteries of DOCA-salt hypertensive rats.
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PMID:Effects of endothelin on resistance arteries of DOCA-salt hypertensive rats. 162 36

The vascular endothelium plays an essential role in regulating the contractility of the adjacent smooth muscle cell through its secretory and metabolic properties. One of these well known properties is the conversion of angiotensin I into angiotensin II. But the endothelium also secretes at least three compounds able to diffuse to the smooth muscle cell and exerting a paracrine action: these are the prostacyclin (PGI2), the endothelium derived relaxing factor (EDRF) and the endothelin 1. The secretion of these different vasoactive compounds by endothelial cells is triggered by mechanical events, such as the shear stress, or by the effect of several humoral factors locally released, for example from platelets. The compound NO (nitric oxide) is produced by the endothelial enzyme NO synthase from its precursor L-arginine, and is responsible for the vasodilatory and antiplatelets properties of EDRF. NO, by activating the soluble guanylate cyclase in the smooth muscle cell, is responsible for the endothelium dependent vasodilatation. We observed in an isolated perfused rat kidney that the compound L-NAME (NG-monomethyl-L-arginine methyl ester), a competitive inhibitor of NO synthase blocking the production of NO, induces renal vasoconstriction and inhibits renin release. This suggests that not only the renal vasoconstriction but also the renal vasodilatation are active processes, permanently regulated by vasoactive compounds such as EDRF. It seems also that EDRF plays an important role in maintaining the secretion of renin. It can be hypothetized that an abnormality in the release or fate of EDRF might perhaps contribute to high blood pressure, by both a direct effect on the vascular tone and an indirect effect on the release of renin, which in turn regulates also the renal and systemic hemodynamics.
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PMID:[Control of vascular tone by the endothelium: the coupling active vasodilation in the kidney to renin secretion]. 163 4

Endothelins (ETs) are a recently discovered family of small proteins that have potent long-lasting vasoconstrictive activities. Increased circulating concentrations of ETs have been found in hypertensive and renal disorders, including pregnancy-induced hypertension (PIH). PIH has been postulated to be the end result of endothelial cell damage and aberrant calcium metabolism. We evaluated the effects of calcium ionophores, calcium channel blockers, and two forms of cellular damage on ET production by human umbilical vein endothelial cells (HUVEC). Cells were grown to confluence and then incubated for 16 h with these treatments: physical trauma ("scratching"), oxidant damage (hydrogen peroxide, 1-20 mM), ionomycin (0.25-2.0 microM), A-23187 (10(-9)-10(-5) M), verapamil (0.22-22.0 microM), and nifedipine (2-200 micrograms/mL). ET production was determined using a commercial RIA that detects ET-1 and ET-2. Physical trauma enhanced ET production, whereas oxidant damage had the opposite effect. Both ionomycin and A-23187 caused concentration-dependent inhibition of ET production. Neither verapamil nor nifedipine consistently altered ET production. We conclude that specific forms of cellular damage can stimulate HUVEC ET production, although oxidant damage may be slightly inhibitory. Thus, enhanced ET levels in PIH may represent endothelial cell activation, rather than damage. HUVEC ET production is regulated in an inverse manner by intracellular calcium concentrations, suggesting a negative feedback from mediators of ET action on cells.
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PMID:The regulation of endothelin production in human umbilical vein endothelial cells: unique inhibitory action of calcium ionophores. 163 63

The role of endothelin (ET-1) in mediating the development of blood pressure was investigated in the spontaneously hypertensive (SHR) rat using the Wistar-Kyoto (WKY) rat as the normotensive control. The following were characterized in both rat strains: age-dependent changes in mean arterial blood pressure (MAP), tissue (blood, lung, heart, and kidney) levels of immunoreactive ET-1 like related peptides (ET-1RP), aortic ring responses to ET-1, and specific high-affinity tissue (lung, atrium, ventricle, aorta, and kidney) binding sites for 125I-labelled ET-1. Commencing at age 10 weeks through to 12 weeks, SHR rats but not WKY rats developed a significant increase in MAP (from 152 +/- 7 to 189 +/- 3 mmHg) (1 mmHg = 133.32 Pa). However, in both WKY and SHR rats immunoreactive levels of ET-1RP increased (100 and 80%, respectively) throughout the same measurement period. The potency of ET-1 to contract aortic rings from SHR rats was slightly but not significantly greater than that for aortic rings from WKY rats, although aortic rings from SHR rats contracted in the presence of 0.5 nM ET-1, while those from WKY rats did not. The levels of immunoreactive ET-1RP were significantly reduced (32%) in the kidney and unchanged in the heart and lung of SHR rats compared with WKY rats. Specific 125I-labelled ET-1 binding sites displayed an increase and a significant decrease (24%) of density in the atrium and ventricle, respectively, a significant increase (31%) of affinity in the lung, and were unchanged in the kidney and aorta of SHR rats compared with WKY rats following the development of hypertension. The lack of a correlation between circulating levels of immunoreactive ET-1RP and the development of hypertension coupled with a lack of significant differences in vascular reactivity suggest that ET-1 is not the sole mediator of hypertension in this animal model. However, the tissue-specific changes in immunoreactive ET-1RP and 125I-labelled ET-1 binding sites suggest that ET-1 may be a partial mediator of hypertension and is subject to compensatory changes in response to the increased total peripheral resistance in SHR rats.
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PMID:Vascular reactivity, tissue levels, and binding sites for endothelin: a comparison in the spontaneously hypertensive and Wistar-Kyoto rats. 164 48

Cloned rat parathyroid cells (PTr cell line) that produce parathyroid hormone-related peptide plus endothelin 1 and primary cultures of human parathyroid cells were tested for growth and differentiation responses to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). High- and low-affinity binding sites for ANP were found on PTr cells; BNP appeared to bind to the same receptors with similar affinities. Either ANP or BNP stimulated production of cGMP and caused a 30% decrease in Na(+)-K(+)-Cl- cotransport. Each peptide increased synthesis and secretion of endothelin 1 by PTr cells in a dose-dependent fashion, but cell growth was not affected. Human parathyroid cells (normal and pathological) also responded to ANP or BNP with an increase in cGMP production. The finding of receptors for natriuretic hormones on parathyroid cells with consequent effects on release of endothelin 1 might be of relevance in understanding the clinical association between hyperparathyroidism and hypertension.
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PMID:Natriuretic peptide receptors regulate endothelin synthesis and release from parathyroid cells. 165 Apr 71


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