THE EFFECTS OF INTRAVENOUS SUBSTANCE-P INFUSION ON HEMODYNAMICS AND REGIONAL BLOOD-FLOW IN CONSCIOUS DOGS

Abstract

Substance P concentrations in plasma increase in response to a meal. The effects of i.v. substance P infusions were investigated in 7 conscious dogs with doses of peptide (7 ng/kg per min) designed to reproduce the normal postprandial circulating increase in substance P. Substance P levels measured by radioimmunoassay increased 8.6 .+-. 4.8 pg/ml in arterial plasma (P < 0.05) and 3.0 .+-. 1.5 pg/ml in mixed venous plasma (P < 0.05). By use of decay equations, the calculated half-life of exogenous immunoreactive substance P was less than 30 s, and this corresponded to rapid abolition of the biologic effects of the peptide upon cessation of the infusion. The integration of the arterial and mixed venous concentration curves allowed calculation of the peripheral inactivation of exogenous immunoreactive substance P as 65.6%. During substance P infusion, mean arterial pressure fell 20 .+-. 6 mm Hg at 5 min from 124 .+-. 6 mm Hg (P < 0.02). Total systemic vascular resistance was 3102 .+-. 196 dynes/s per cm5 basally, and it fell by 667 .+-. 137 dynes/s per cm5 (P < 0.05) at 10 min. Plasma glucose, insulin and cortisol concentrations did not change significantly from 83 .+-. 4 mg/dl, 5.1 .+-. 1.0 .mu.U/ml and 4.6 .+-. 0.5 .mu.g/dl, respectively. Radioactive 15 .mu.m microspheres injected at 0, 20 and 50 min into the infusion allowed for identification of statistically significant (P < 0.05) increases in blood flow to the adrenal gland and the muscular layers of the fundus and the ileum. Thus the infusion of substance P to reproduce postprandial circulating levels of this peptide was followed by an orderly sequence of hemodynamic alterations in the conscious dog. Regional blood flow changes were seen in the muscular layers of the fundus and ileum, which are regions of high substance P concentration.