Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of prostanoids in the constrictor effect of calcium ionophore A23187, endothelin-1 and vasopressin in rings of thoracic aorta obtained from normotensive rats and rats with aortic coarctation-induced hypertension. Isometric tension was measured in aortic rings bathed in buffer with and without indomethacin (10 microM), CGS13080 (10 microM) or SQ29548 (1 microM) to inhibit cyclooxygenase and thromboxane synthase and to block TxA2-PGH2 receptors, respectively. Increases in tension elicited by A23187 and vasopressin in aortic rings from hypertensive rats exceeded responses in rings from normotensive rats. A23187-induced contractions were virtually abolished by indomethacin and SQ29548, and slightly attenuated by CGS13080. These agents also attenuated the contractions elicited by endothelin but not by vasopressin. According to these data, a prostanoid(s) agonist for TxA2-PGH2 receptors contributes to the constrictor effect of A23187 in aortic rings of hypertensive rats, and of endothelin in aortic rings of normotensive and hypertensive rats. Moreover, the expression of prostanoid-mediated contractions as it pertains to the aortic response to A23187 is greatly increased in hypertensive rats.
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PMID:Prostanoid-mediated vascular contraction in normotensive and hypertensive rats. 142 79

Endothelin-1 inhibits sodium and water transport systems in the inner medullary collecting duct. Endothelin-1 levels are reduced in the medulla of spontaneously hypertensive rats (SHR), raising the possibility that decreased inner medullary collecting duct production of endothelin-1 could contribute to inappropriate sodium and water retention. In the current study, immunoreactive endothelin-1 was measured in the urine, blood, and eluates from cortex and outer and inner medulla of SHR before (age 3-4 weeks) and after (age 8-9 weeks) the development of hypertension and in age-matched Wistar-Kyoto (WKY) controls. There was no difference in endothelin-1 levels between prehypertensive SHR and WKY rats. In contrast, 8-9-week-old SHR had significantly reduced endothelin-1 in the urine and outer and inner medulla, but not in the cortex or serum compared with those of WKY controls. Furthermore, inner medullary collecting duct cells from 8-9-week-old SHR, either acutely isolated or cultured, released less endothelin-1 than did those from WKY rats. Finally, the level of endothelin-1 messenger RNA was only reduced in the inner medulla and in inner medullary collecting duct cells from 8-9-week-old SHR. In summary, renal medullary, and in particular terminal collecting duct, endothelin-1 production is reduced in SHR only after the development of hypertension. Such decreases in inner medullary collecting duct endothelin-1 production may contribute to the hypertensive state in SHR.
Hypertension 1992 Nov
PMID:Alterations in renal endothelin-1 production in the spontaneously hypertensive rat. 142 17

The term X syndrome involves several dilemmas. The terminological dilemma is that this term is used to describe microvascular angina pectoris, as well as Reaven's metabolic-hormonal syndrome and our 5H syndrome [association of hyperinsulinism with arterial hypertension, hyperlipoproteinaemia, hyperglycaemia (NIDDM) and hirsutism]. It is probable that the coronary X syndrome is frequently conditioned by the hormonal-metabolic X syndrome. The pathogenetic dilemma is that it is not clear why in microvascular angina pectoris the coronary circulation does not possess an adequate reserve for vasodilatation during exercise or in response to some pharmacological stimuli. This could condition hyperinsulinism in hypertonic subjects with NIDDM with an early disorder of paracrine endothelial relaxation mechanisms (EDRF-NO), with a predominance of vasoconstrictor mechanisms (endothelin-1). In Reaven's syndrome X it is not clear whether insulin resistance of the postreceptor type is a primary inborn phenomenon which is compensated by insulin hypersecretion or whether it is a secondary phenomenon, which develops ex post and by which the target tissues defend themselves against an excessive effect of insulin (e.g. down regulation receptors) in primary disorders of its secretion.
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PMID:[The dilemma of syndrome X]. 149 65

In one third of patients who suffered an infarction NIDDM and arterial hypertension are present. In the absolute majority of patients with IHD, as apparent from the IRI and C-peptide response after a glucose load, hyperinsulinism is present. The blood sugar response can have the character of diabetes or of impaired glucose tolerance, the curve may be very flat or normal while the IRI and C-peptide response are excessive. Hyperinsulinism has a hypersecretory origin as suggested by the concurrently elevated C-peptide level but also reduced insulin utilization in the liver and peripheral target organs. Hyperinsulinism is thus a regular associated phenomenon of IHD and is a special risk factor independent on hyperglycaemia and associates with the other main risk factors of IHD such as arterial hypertension, HPLP (android obesity), hyperglycaemia (NIDDM) and hirsutism as a manifestation of a hyperandrogenic state in the female organism with the syndrome of polycystic ovaries. Hyperinsulinism plays an indirect role in the pathogenesis of coronary syndrome via the main risk factors (5H syndrome--hyperinsulinism, hypertension, HPLP, hyperglycaemia, hirsutism) and also directly by its action on endothelial paracrine mechanism of the coronary circulation where in the early stage vasoconstrictor factors predominate (endothelin-1, PGF2-alpha) over physiological vasodilatating factors (EDRF-NO, PGE2, PGI2) and this leads then to functional spasms. It seems that also the coronary X syndrome develops very frequently on the background of the hormonal metabolic X syndrome or the 5H syndrome.
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PMID:[Hyperinsulinism and the coronary syndrome]. 149 68

As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension and hypercholesterolaemia. All three conditions are associated with a decreased basal and simulated release of endothelium-derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of a cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The circulating levels of endothelin-1 on the other hand are not increased in experimental and human hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduced endothelium-dependent relaxations to aggregating platelets, serotonin and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension and hypercholesterolaemia may have important clinical implications for the pathogenesis of cardiovascular disease.
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PMID:Age, hypertension and hypercholesterolaemia alter endothelium-dependent vascular regulation. 150 46

The purpose of the present experiments was to study the effects of endothelin-1 (ET-1) on vascular permeability and the involvement of the cyclooxygenase metabolites in the vascular responses to ET-1. Bolus intravenous injection of ET-1 (0.1-1.0 nmol/kg) into conscious rats induced immediate hypotension lasting for 30 s followed by sustained dose-dependent hypertension. A low dose of ET-1 (0.1 nmol/kg) did not modify the hematocrit value but the 1.0-nmol/kg dose increased the hematocrit value from 39.7 to 44.4%. Pretreatment of the animals with BM-13505 (1 mg/kg), a thromboxane A2 (TxA2) receptor antagonist, prolonged the duration of the hypotensive response to ET-1 (1.0 nmol/kg) but had no effect on the pressor response. Pretreatment with OKY-046 (10 mg/kg), a TxA2 synthesis inhibitor, or indomethacin (10 mg/kg), a cyclooxygenase inhibitor, had no significant effect on ET-1-induced changes in blood pressure. Evans blue dye extravasation, a marker of vascular permeability, increased up to 235% over control levels in specific vascular beds including the upper and lower bronchi, stomach, duodenum and kidney of ET-1 (1.0 nmol/kg)-treated animals. Pretreatment of the animals with BM-13505, OKY-046 or indomethacin reduced by 60-100% the Evans blue extravasation in these tissues. These results suggest that the effect of ET-1 on vascular permeability is partly mediated and/or modulated by the secondary release of TxA2, whereas its action on arterial blood pressure appears to be independent from prostanoid release in conscious rats.
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PMID:Endothelin-1 enhances vascular permeability in conscious rats: role of thromboxane A2. 151 34

To assess possible roles of endothelin in the regulation of blood pressure, we studied effects of a subpressor dose of endothelin-1 (3 micrograms/kg/day) on chronic blood pressure responses to infusion of angiotensin II and norepinephrine in rats. Rats were infused with angiotensin II at a subpressor dose (400 micrograms/kg/day i.p.) or with norepinephrine at a subpressor dose (360 micrograms/kg/day i.p.) for 6 days. Systolic blood pressure was significantly elevated during combined infusion of endothelin-1 and angiotensin II, whereas endothelin-1 alone or angiotensin II alone failed to induce any significant changes in systolic blood pressure compared with vehicle alone. This effect was sustained for the whole experimental period and was not associated with any significant changes in body weight, fluid intake, urine volume, or urinary electrolyte excretion. In contrast, combined infusion of endothelin-1 and norepinephrine failed to elevate systolic blood pressure, and no significant difference in systolic blood pressure was observed for the whole experimental period among the four groups of rats with endothelin-1 in combination with norepinephrine, endothelin-1 alone, norepinephrine alone, and vehicle alone. The present results indicate that angiotensin II and endothelin-1, but not norepinephrine and endothelin-1, work synergistically to raise the blood pressure and also suggest the possibility that endothelin-1 may modulate blood pressure control.
Hypertension 1992 Sep
PMID:Endothelin-1 augments pressor response to angiotensin II infusion in rats. 151 47

We tested the hypothesis that increased systemic vascular resistance in spontaneously hypertensive rats may be secondary to enhanced phospholipase C activity in response to vasoconstrictor stimuli. Activation of phospholipase C by angiotensin II (Ang II), thromboxane A2, arginine vasopressin, and endothelin-1 was compared in cultured glomerular mesangial cells and mesenteric vascular smooth muscle cells taken from 13- to 14-week-old hypertensive and normotensive Wistar-Kyoto rats (blood pressure, 185 +/- 1 versus 135 +/- 2 mm Hg). Phospholipase C was assessed by measuring cytosolic free calcium and by the accumulation of radiolabeled inositol phosphates. Basal cytosolic calcium did not differ between mesangial cells taken from both strains but was greater in smooth muscle cells from hypertensive rats (210.1 +/- 8.2 versus 149.2 +/- 4.7 nM). The responsiveness of cytosolic calcium and inositol phosphate accumulation to Ang II was significantly enhanced in mesangial cells from hypertensive rats (10(-7) M Ang II: peak increase of calcium, 1,266 +/- 181 versus 603 +/- 93 nM; percent increment of inositol phosphates at 1 minute, 266 +/- 26 versus 98 +/- 10%). Vascular smooth muscle cells from hypertensive rats, when compared with normotensive rats, showed a similar augmentation of Ang II-stimulated intracellular calcium and inositol phosphates. Thromboxane A2-induced enhancement of intracellular calcium and inositol phosphate accumulation in vascular smooth muscle cells was also greater in hypertensive animals. However, the responses to vasopressin and endothelin in mesangial or vascular smooth muscle cells did not differ between the normotensive and hypertensive animals. There was no significant difference in Ang II receptor number and affinity between hypertensive- and normotensive-derived mesangial cells. We conclude that genetically increased blood pressure in rats may be secondary to enhanced post-receptor signaling in glomerular mesangial cells activated by Ang II and to enhanced signaling in vascular smooth muscle cells stimulated by either Ang II or thromboxane A2.
Hypertension 1992 May
PMID:Phospholipase C responses in cells from spontaneously hypertensive rats. 156 63

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 salt intake on the hypertensive response to long-term infusion of endothelin-1 was investigated. Chronically instrumented male Sprague-Dawley rats (325-375 g) were used in a 15-day protocol that included 3 control days followed by 7 days of endothelin-1 infusion at 5.0 pmol.kg-1.min-1 and 5 days of recovery. Rats were maintained on either a normal sodium chloride intake (2.0 meq Na+ per day; normal sodium) or a high sodium chloride intake (6.0 meq Na+ per day; high sodium) throughout the protocol. Control rats received normal or high sodium intakes but not endothelin-1. In high-sodium rats, endothelin-1 produced a significant increase in mean arterial pressure and total peripheral resistance; a significant bradycardia was observed only on the first day after the start of the endothelin-1 infusion. Cardiac output, stroke volume, water balance, and urinary sodium and potassium excretion remained unchanged. Termination of endothelin-1 infusion resulted in rapid normalization of both arterial pressure and peripheral resistance. In contrast, normal sodium rats exhibited no alteration in mean arterial pressure, heart rate, total peripheral resistance, stroke volume, water balance, or urinary sodium and potassium excretion throughout the endothelin-1 infusion protocol. The hypertension produced by endothelin-1 infusion cannot be explained by alterations in salt or water balance since endothelin-1 infusion in high sodium animals produced significant increases in mean arterial pressure with no observable changes in water or electrolyte balance. These results indicate that endothelin-induced hypertension in conscious rats is a salt-dependent model of hypertension.
Hypertension 1992 Jun
PMID:Salt-dependency of endothelin-induced, chronic hypertension in conscious rats. 159 49


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