Coronary vascular and myocardial effects of substance P in hypercholesterolemic rabbits.
Age-matched male New Zealand white rabbits (n = 16) were allocated to two groups: group 1 (n = 8) received a standard rabbit diet; group 2 (n = 8) received a 2% cholesterol-enriched diet. After 8 weeks of prescribed diet, hearts were excised and placed on a constant perfusion pressure Langendorff-type apparatus. Coronary flow, left ventricular pressure, and isovolumic dP/dt were continuously measured. Baseline recordings were made and then a single 5 nmol bolus dose of substance P was delivered into the coronary perfusate. Mean serum cholesterol levels in group 1 were 53 +/- 17 (SEM) mg.dl-1, in group 2 1438 +/- 143 mg.dl-1. In group 1, the injection of substance P caused mean coronary flow to increase 39 +/- 6%, mean coronary vascular resistance to decrease 28 +/- 3%, and mean dP/dt to increase 11 +/- 4%. In group 2, coronary flow increased 57 +/- 13%, coronary vascular resistance decreased 33 +/- 5%, and dP/dt increased 17 +/- 4%. Within groups, values changed significantly from baseline but these changes were not significantly different between groups. The duration of coronary flow response was 113 +/- 20 s in group 1 and 63 +/- 8 s in group 2. Substance P is a potent dilator of coronary resistance vessels and has positive inotropic effects in the rabbit. High levels of cholesterol exposure do not alter the magnitude of substance P-induced vasodilation, but the duration of the response is shortened.
Maley
R H
RH
Department of Surgery, University of Kentucky College of Medicine, Lexington 40536-0084.
Vrettos
A M
AM
Arden
W A
WA
Chein
S
S
Salley
R K
RK
Gross
D R
DR
D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003331:Coronary Vessels / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D008297:Male; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002791:Cholesterol, Dietary; D014662:Vasoconstrictor Agents; D013373:Substance P