Plasma endothelin-1 response to acute hypotension induced by vasodilating agents.
Cyclic GMP (cGMP) dependent vasodilating agents (natriuretic peptides, nitric oxide) inhibit secretion of endothelin-1 (ET-1) in cultured endothelial cells. However, in circulatory conditions associated with acute hypotension, a marked increase in plasma ET-1 has repeatedly been observed. Therefore, after administration of cGMP-dependent agents in hypotensive dose, the net effect of these opposing influences on ET-1 release may shed light on the mechanisms determining circulating levels of this peptide. We have studied the effect of a hypotensive dose of atrial natriuretic peptide (n = 16), 8-Br-cGMP (n = 5), and papaverin (n = 7) on plasma ET-1 in anesthetized dogs. All agents produced marked increases in the peptide level at the end of infusion (178, 280, and 240% of the last preinfusion level, respectively) and a mean arterial blood pressure (MAP) decrease of 19, 18, and 42 mmHg (1 mmHg = 133.3 Pa), respectively. In all three protocols, plasma ET-1 continued to rise when the hypotensive agent was discontinued and remained elevated for 2-3 h postinfusion, even though MAP was normalized. There was a close positive correlation between the maximal increment in plasma ET-1 and the maximal decrease in MAP (r = 0.67, p < 0.001). These results show that acute hypotension due to directly acting vasodilators is a potent stimulus for systemic release of ET-1, even when due to agents known to inhibit ET-1 production in cultured endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, McGill University, Montréal, QC, Canada.
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P
Cernacek
D J
DJ
Stewart
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M
Levy
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology; D001786:Blood Glucose; D001794:Blood Pressure; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000097:blood* / Q000737:chemistry; D005260:Female; D005919:Glomerular Filtration Rate; D007022:Hypotension / Q000097:blood* / Q000503:physiopathology; D008297:Male; D010208:Papaverine / Q000494:pharmacology
D001786:Blood Glucose; D016232:Endothelins; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D010208:Papaverine; D006152:Cyclic GMP