Effects of Bradykinin and Autonomic Nervous System Inhibition on Systemic and Regional Hemodynamics in the Unanesthetized Rhesus Monkey

¹ Division of Clinical Pharmacology, Department of Medicine and Pharmacology and the Cardiovascular Research Institute, University of Califomia San Francisco Medical Center, San Francisco, Calitomia 94122

Studies were performed in unanesthetized monkeys to determine if bradykinin infusions reproduce the circulatory events of early endotoxemia. Kinin infusions before and during autononiic ganglionic blockade with trimethaphan were significantly correlated (P <0.05) with decreases in mean arterial pressure. Kinin infusion at 15-18, µg/kg min^- produced 26 mm Hg fall in mean blood pressure at 3 min, due to fall in total peripheral resistance of 14 mm Hg/liter min^-1. Heart rate rose 23 beats/min. After 10 minutes of infusion, peripheral resistance had returned to base line, blood pressure remained low due to fall in cardiac output of 0.53 liters/min (P <0.01). Ganglionic blockade prevented recovery of resistance. Plasma bradykinin levels at 3 and 10 minutes were 14 and 15 µg/ml, respectively. Regional and systemic hemodynamic effects of kinin (15-18 µg/kg min were determined in 10 monkeys. After 10 minutes of infusion, bradykinin produced systemic effects. Regional flow measurement (by radioactive microsphere technique) demonstrated a pattern similar to that seen during hemorrhage. Canglionic blockade lowered mean arterial pressure 33 mm Hg by generalized vasodilatation, Kinin infusion then resulted in further vasodilatation and fall in blood pressure of 12 mm Hg, and cardiac output of 0.74 liters/min. Regional flow distribution during combined infusion was similar to that seen during early endotoxemia.

Submitted on April 8, 1971
Accepted on August 6, 1971