Disparate effects of substance P on systemic and coronary beds in conscious dogs.

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Abstract
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 less than 0.01) in cardiac output by 22 +/- 5%, in decreases (p less than 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 less than 0.01) by 35 +/- 7% and left ventricular dP/dt (p less than 0.05) by 13 +/- 4%. In this situation, coronary blood flow decreased (p less than 0.01) by 19 +/- 4% and coronary vascular resistance increased (p less than 0.05) by 13 +/- 5%. Myocardial oxygen delivery was reduced (p less than 0.05) by 13 +/- 5% and the arteriovenous oxygen difference widened (p less than 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 less than 0.01) by 12 +/- 3% respectively. Under these conditions, coronary blood flow decreased (p less than 0.01) by 37 +/- 5% and coronary vascular resistance increased (p less than 0.01) by 47 +/- 8%, which were more (p less than 0.01) than control responses. In this situation, myocardial oxygen delivery was reduced (p less than 0.01) by 37 +/- 4% and the arteriovenous oxygen difference widened (p less than 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.