Cardiovascular responses and interactions by neuropeptide Y in rats with congestive heart failure.
Neuropeptide Y (NPY) has been shown to potentiate the effects of various vasoactive agents in both in vitro and in vivo experiments. The present study was designed to investigate the potentiation effects of NPY on various vasoconstrictive agents and the influence of NPY on the dilatation effects of endothelin-1 in rats with congestive heart failure (CHF). CHF was induced by left coronary artery ligation. Sham-operated rats subjected to thoracotomy served as normal controls. Experiments in conscious rats were performed 4-6 weeks after coronary artery ligation or sham operation. The pressor responses of intravenous phenylephrine (12.5 nmol/kg), endothelin-1 (400 pmol/kg) and angiotensin II (10 ng) but not tyramine (40 micrograms) were significantly decreased in CHF rats compared with sham-operated rats (p < 0.01). In sham-operated rats, subthreshold dose of NPY (0.1 microgram/kg/min) potentiated the pressor responses of all the agonists (p < 0.05). In CHF rats, significant enhancement of mean arterial pressure (MAP) by subthreshold dose of NPY was observed with angiotensin II (p < 0.05). The MAP was enhanced by 45.4% in CHF and 40.6% in sham-operated rats respectively. NPY did not enhance the pressor responses induced by phenylephrine, endothelin-1 or tyramine in CHF rats. The initial decrease of MAP after bolus injection of endothelin-1 was observed in both CHF and sham-operated control rats, and magnitude of this response was similar in both groups. Subthreshold dose of NPY significantly reduced the vasodilatation effect of endothelin-1 in CHF (p < 0.05) but not in normal control rats. We conclude that NPY potentiates pressor effects of angiotensin II and reduces vasodilatation effects of endothelin-1 in rats with CHF. These effects of NPY may contribute to the increased vascular tone in CHF.
Feng
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QP
Department of Pharmacology, University of Gothenburg, Sweden.
Sun
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XY
Hedner
T
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology*; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D019332:Endothelin-1; D009478:Neuropeptide Y; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents