Haemodynamic effects of intracoronary neuropeptide Y in dogs: resistance to alpha adrenergic blockade.
OBJECTIVE
Neuropeptide Y is a peptide isolated from brain and neural tissue around human coronary arteries. It has been shown to produce coronary vasoconstriction and myocardial ischaemia. The purposes of this study were (a) to determine whether the vasoconstriction induced by neuropeptide Y was mediated by alpha adrenergic receptors in vivo, and (b) to determine the time course of the effect and whether it was reproducible with a second administration.


METHODS
Neuropeptide Y (200 micrograms over 2 min) was given by intracoronary injection on two occasions 1 h apart to group I dogs (control). In group II the second dose was preceded by treatment with the alpha blocker phenoxybenzamine (4-10 mg.kg-1). The time course and magnitude of the effect was studied in the two groups to determine the effects of alpha blockade and of repeated neuropeptide Y dosage.


METHODS
14 mongrel dogs (n = 7 per group) were anaesthetised with chloralose for a left thoracotomy to measure coronary blood flow, aortic pressure, left ventricular pressure, and heart rate.


RESULTS
Reproducible prolonged increases in coronary vascular resistance occurred after the first [33(SD 18)%] and second [34(17)%] doses of neuropeptide Y. At this infusion rate mean aortic pressure increased with each dose by 21% and coronary blood flow decreased by 7%. In group II dogs, phenoxybenzamine given intravenously 20 min after the first dose of neuropeptide Y reduced mean aortic pressure by 15-20 mm Hg. In this group neuropeptide Y also caused reproducible increases in coronary vascular resistance before (36%) and after (46%) alpha blockade.


CONCLUSIONS
Neuropeptide Y constricts coronary arteries in vivo by mechanisms that do not require intact alpha adrenergic receptors, and the coronary vasoconstriction was prolonged and reproducible.
Stack
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RK
Department of Medicine (Cardiology), Emory University School of Medicine Carlyle Fraser Heart Center, Crawford Long Hospital of Emory University, Atlanta, Georgia 30365.
Patterson
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D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D009478:Neuropeptide Y; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine