Coronary constriction due to neuropeptide Y: alleviation with cyclooxygenase blockers.
Intra-arterial administration of neuropeptide Y (NPY), a peptide endogenous to sympathetic nerves, increases coronary vascular resistance by 30-40%. To test whether blockade of prostaglandin synthesis altered the severity of the NPY-induced coronary vasoconstriction, dogs (n = 25) were anesthetized and instrumented to record hemodynamic parameters. In control animals (n = 11) paired infusions of NPY (42 nmol/3 min) were given at 0 and 120 min. NPY produced similar increases in coronary resistance by 10 min, 31 +/- 7% (mean +/- SD) with the first dose vs. 32 +/- 12% with the second dose. The increases in resistance were due to an initial decrease in coronary flow (10 +/- 6%) followed by a prolonged increase in aortic pressure (15-20% over 20 min). Each infusion of NPY decreased heart rate (-10 +/- 7%) but did not alter left ventricular dP/dt. The effects of NPY lasted 40-60 min. In a separate group, a cyclooxygenase inhibitor (COI), indomethacin (n = 6) or ibuprofen (n = 8), was given 1 h before the second dose of NPY. The increases in coronary resistance were blunted significantly after cyclooxygenase blockade from a predrug value of 36 +/- 13 to 19 +/- 12%. In these treated animals, the decrease (-12 +/- 6%) in coronary blood flow seen with the first dose of NPY was prevented (4 +/- 14%) during the second dose (P less than 0.05). Of the two drugs, ibuprofen appeared to restore coronary flow more than did indomethacin. Neither drug affected the base line or the NPY-elicited changes in aortic pressure, heart rate, dP/dt, or myocardial oxygen demands.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
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Carlyle Fraser Heart Center, Crawford Long Hospital of Emory University, Department of Medicine, Atlanta, Georgia.
Patterson
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D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology*; D010101:Oxygen Consumption; D014661:Vasoconstriction
D016861:Cyclooxygenase Inhibitors; D009478:Neuropeptide Y; D007052:Ibuprofen; D007213:Indomethacin