Opposite effects of substance P on conductance and resistance coronary vessels in conscious dogs

Abstract

The effects of substance P (SP) on epicardial coronary diameter (CD) and coronary blood flow (CBF) were examined in conscious dogs. SP (5.0 ng/kg) induced transient increases (P less than 0.01) in CBF by 139 +/- 19% from 26.5 +/- 1.5 ml/min followed by sustained decreases (P less than 0.01) averaging 22 +/- 2% when mean arterial pressure had returned to preinjection base line. CD increased (P less than 0.01) by 6.7 +/- 1.4% from 3.47 +/- 0.35 mm. After ganglionic blockade with hexamethonium (35 mg/kg), the transient increases (P less than 0.01) in CBF (95 +/- 10% from 28.6 +/- 1.9 ml/min) were smaller (P less than 0.05), but the late decreases (P less than 0.01) in CBF averaged 23 +/- 3%, similar to responses before ganglionic blockade. Increases (P less than 0.01) in CD (4.1 +/- 0.7% from 3.49 +/- 0.35 mm) were smaller (P less than 0.05) than before ganglionic blockade. During steady-state effects of SP (5.0 ng.kg-1.min-1) under ganglionic blockade, CBF fell (P less than 0.01) by 39 +/- 3% from 26.4 +/- 2.3 ml/min, but CD increased (P less than 0.01) by 6.6 +/- 1.6% from 3.45 +/- 0.40 mm. Additional experiments indicated that coronary sinus blood oxygen content fell and myocardial arteriovenous O2 difference increased during steady-state effects of SP under ganglionic blockade. Cyclooxygenase inhibition did not alter coronary responses to SP. Endothelial denudation abolished increases in CD after SP. Therefore, under steady-state conditions and in the absence of autonomic reflexes, SP is a potent endothelium-dependent dilator of conductance coronary vessels but paradoxically a constrictor of resistance coronary vessels.