Contribution of hemodynamic variables to the lowering of blood pressure by substance P in the anesthetized rat.

The radioactive microsphere technique was used to determine the contribution of acute changes in systemic hemodynamic variables to the lowering of blood pressure caused by substance P in rats anesthetized with urethane. Infusion of 0.74 nmol/kg/min of substance P caused a decrease of blood pressure, cardiac output, stroke volume and blood flow to most tissues. Total and regional vascular resistances were not affected. Heart rate was increased. These results suggest that the lowering of blood pressure caused by substance P occurs as a result of the decreased stroke volume and cardiac output. The most likely explanation for the decreased stroke volume is a decreased venous return. Several studies have shown that substance P has a direct effect to dilate peripheral arteries. Since substance P dilates arteries, one would expect a decrease of peripheral vascular resistance. The results of this study suggest, however, that counter-regulatory processes, elicited in response to the vasodilatation and direct effects of substance P on sympathetic ganglia to increase the sympathetic nervous system activity, offset the direct effect of substance P on arteries that would otherwise cause a decrease of peripheral vascular resistance.