DISPARATE EFFECTS OF SUBSTANCE-P ON SYSTEMIC AND CORONARY BEDS IN CONSCIOUS DOGS

Background. Previous studies in anesthetized animals indicated that substance P is a coronary and peripheral vasodilator. However, coronary vasodilation was only transient perhaps because of tachyphylaxis. In the present study, the steady-state effects of intravenous substance P on systemic and coronary beds were investigated in conscious, instrumented dogs. Methods and Results. With intact autonomic reflexes, 5 ng/kg/min i.v. substance P resulted in increases (p < 0.01) in cardiac output by 22 +/- 5%, in decreases (p < 0.01) in mean arterial pressure by 9 +/- 2%, and in total peripheral resistance by 23 +/- 4% 7-9 minutes after the beginning of substance P infusion. Heart rate increased (p < 0.01) by 35 +/- 7% and left ventricular dP/dt (p < 0.05) by 13 +/- 4%. In this situation, coronary blood flow decreased (p < 0.01) by 19 +/- 4% and coronary vascular resistance increased (p < 0.05) by 13 +/- 5%. Myocardial oxygen delivery was reduced (p < 0.05) by 13 +/- 5% and the arteriovenous oxygen difference widened (p < 0.01). After ganglionic blockade, increases in cardiac output, heart rate, and left ventricular dP/dt with substance P administration were abolished, but total peripheral resistance and mean arterial pressure decreased (p < 0.01) by 12 +/- 3% and 11 +/- 3%, respectively. Under these conditions, coronary blood flow decreased (p < 0.01) by 37 +/- 5% and coronary vascular resistance increased (p < 0.01) by 47 +/- 8%, which were more (p < 0.01) than control responses. In this situation, myocardial oxygen delivery was reduced (p < 0.01) by 37 +/- 4% and the arteriovenous oxygen difference widened (p < 0.01). Intracoronary infusion of substance P (0.4 ng/kg/min) resulted in significant and sustained decreases in coronary blood flow, which were similar before and after ganglionic blockade. Conclusions. Thus, in conscious dogs, systemic vasodilation is the prevailing effect of substance P, but paradoxically, this peptide simultaneously elicits coronary vasoconstriction.