Effects of neurotensin and neuropeptide Y on coronary circulation and myocardial function in dogs.
This study analyzed the effects of the neuropeptides, neurotensin, and human and porcine analogue, neuropeptide Y, in anesthetized open-chest dogs. The left anterior descending coronary artery was cannulated and perfused at constant pressure via a blood reservoir. Flow to the coronary cannula was measured by an electromagnetic flowmeter, and regional segment lengths were measured by sonomicrometer crystals. Neurotensin injected into the coronary cannula resulted in a dose-dependent increase of coronary flow; neuropeptide Y resulted in a decrease of coronary flow. Because these changes in flow were not explained by systemic hemodynamic effects or alterations in regional myocardial function, they were considered to be coronary dilatation or constriction. Coronary dilatation by neurotensin was not prevented by alpha- or beta-adrenoceptor blockade but was completely abolished by indomethacin or by lowering coronary perfusion pressure to 35 mmHg when depressed systolic segment shortening indicated myocardial ischemia. Coronary constriction by neuropeptides Y persisted at coronary perfusion pressure of 35 mmHg and was only attenuated by indomethacin. We conclude that in contrast to systemic effects, coronary vasodilatation by neurotensin is mediated by a prostanoid product of cyclooxygenase. Preactivation of the prostaglandin system may explain why neurotensin lost its coronary dilator effect during myocardial ischemia. Neuropeptide Y may elicit coronary constriction in addition to mechanic reduction of coronary flow resembling severe coronary stenosis.
Ertl
G
G
Medizinische Klinik, Universität Würzburg, Germany.
Bauer
B
B
Becker
H H
HH
Rose
G
G
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D009478:Neuropeptide Y / Q000494:pharmacology*; D009496:Neurotensin / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
D009478:Neuropeptide Y; D011453:Prostaglandins; D009496:Neurotensin; D007213:Indomethacin