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)

Alpha-human atrial natriuretic polypeptide (alpha-hANP) was applied to 16 clinical patients, 6 patients with essential hypertension, 7 patients with congestive heart failure and 3 patients with cirrhosis. Following intravenous bolus injection of 400 micrograms of synthetic alpha-hANP, a hypotensive effect of very rapid onset was found, which was more potent in the hypertensive patients than in the normotensive cases. Cardiac functions were improved significantly with a similar time course as the depressor response in the cases of heart failure or hypertension. Hemodynamic observations showed a marked increase in cardiac output, cardiac index, stroke volume, ejection fraction and ejection rate, and a concomitant decrease of the pressure in the right side of the heart and pulmonary circulation in these subjects. In addition, the renal response to alpha-hANP induced obvious increases in urine volume, electrolytes and creatinine excretions in all the subjects. Finally, plasma levels of aldosterone, Arg-vasopressin and noradrenaline were also altered by alpha-hANP. No significant side effects were registered. The above result confirms the therapeutic actions of alpha-hANP in human subjects and opens the possibility to research alpha-hANP as a powerful pharmacological tool as well as potential new medicine for human disorders.
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PMID:Therapeutic actions of alpha-human atrial natriuretic polypeptide in 16 clinical cases. 295 43

Prolonged stimulation of tissues by adrenergic agonists may lead to diminished responsiveness of the tissues to subsequent activation by catecholamines; this phenomenon has been termed desensitization or tachyphylaxis. We have examined the in vivo consequences of prolonged stimulation of vascular alpha-adrenergic receptors in rats harboring pheochromocytoma, a tumor that secretes catecholamines. In both early (3-4 weeks after implantation) and late (6-7 weeks after implantation) stages of tumor development, New England Deaconess Hospital rats with transplanted pheochromocytomas developed hypertension and tachycardia and had plasma dopamine and norepinephrine concentrations markedly greater than controls. In both these stages of pheochromocytoma, pressor responses to several vasoconstrictors were examined after pithing. Rats with the tumor were found to become progressively subsensitive to alpha-adrenergic agonists. In the early phase of pheochromocytoma, loss in sensitivity was found for both alpha 1- and alpha 2-adrenergic agonists, whereas responsiveness to the nonadrenergic vasoconstrictors Arg-vasopressin and angiotensin-II was intact (homologous desensitization). However, in the later stage of pheochromocytoma, pressor responses to all these vasoconstrictive agents and also to stimulation of the complex sympathetic outflow were found to be subsensitive (heterologous desensitization). In plasma membranes prepared from mesenteric arteries of early stage tumor-bearing rats, [3H]prazosin binding sites were significantly decreased to 150 +/- 12 fmol/mg vs. 234 +/- 19 fmol/mg in controls. [3H]Yohimbine binding sites were not significantly altered. Our results show that both postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses can be specifically attenuated in the presence of chronically elevated endogenous catecholamine levels produced by pheochromocytoma and that each alpha-receptor subtype may be differently regulated in the development of desensitization.
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PMID:Desensitization of postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses in rat harboring pheochromocytoma. 303 68

Cytosolic free Ca2+ concentrations [( Ca2+]i) were measured in smooth muscle cells (SMC) from spontaneously hypertensive rats (SHR) and age and sex matched Wistar-Kyoto rats (WKY). Resting levels of [Ca2+]i were 114 +/- 6 nM and 116 +/- 5 nM in SMC from WKY and SHR, respectively. Angiotensin II (AII) induced a dose-dependent large increases in [Ca2+]i in SMC. There were no significant differences in resting or AII-stimulated levels of [Ca2+]i when SMC from WKY and SHR were compared. Arg-vasopressin (AVP) caused a similar but smaller [Ca2+]i increase than AII in SMC. AVP caused larger [Ca2+]i increases in SMC from SHR than in SMC from WKY. Although concentrations of AVP higher than those ordinarily detected in plasma were necessary to obtain different responses between SHR and WKY, these differences may be related to the pathogenesis of hypertension.
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PMID:Vasopressin-induced calcium increases in smooth muscle cells from spontaneously hypertensive rats. 402 31

Hypertension is a major risk factor in the development of cardiovascular disease. Adenovirus gene transfer of endothelin-1 (Ad.CMV.ET-1) in rats produced significant (5-fold) increases in plasma ET-1 and systemic blood pressure (46%) 4 days after viral administration, compared with beta-galactosidase (Ad.CMV.beta-gal) injected as control. The density (B(max)) of the ET receptor ET(A) measured in aortas was reduced significantly by more than 50% to 17+/-2 fmol.mg(-1) of protein for the Ad.CMV.ET-1 group compared with 39+/-6 fmol x mg(-1) of protein for the control. There was no change in the density of the smaller population of the ET(B) sub-type. In agreement, the ratio of ET(A) mRNA to cyclophilin mRNA (a housekeeping gene) measured by Northern analysis was reduced in Ad.CMV.ET-1 rats compared with controls. The ratio of mRNA encoding the ET(B) sub-type did not change. ET-1 vasoconstriction was significantly reduced (P<0.05) in aortas from Ad.CMV.ET-1-treated rats [pD(2)=8.67+/-0.14 (where pD(2) is -log(10)EC(50)); n=11] versus the control (pD(2)=9.11+/-0.06; n=14) but there was no significant difference in the potency of two other vasoconstrictors tested (noradrenaline and Arg-vasopressin), indicating this was a specific effect on ET receptors. There was no change in the affinity of ET-1 binding to either receptor sub-type in the experimental group compared with the control, demonstrating that the attenuation in the constrictor response is the result of the reduced density of receptors rather than a change in affinity. The results show that ET(A) (but not ET(B)) receptors are modulated in this experimental model of hypertension and provide further evidence for selective blockade of the ET(A) receptor as a therapeutic strategy.
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PMID:Elevated systemic levels of endothelin-1 and blood pressure correlate with blunted constrictor responses and downregulation of endothelin(A), but not endothelin(B), receptors in an animal model of hypertension. 1219 22