Effects of RA642, a new central pressor agent, on renal sympathetic nerve activity and blood pressure during hemorrhagic shock in rabbits

This experiment was designed to evaluate effects of RA642, a pyrimido-pyrimidine derivative, on renal nerve activity (RNA), mean blood pressure (MBP), central venous pressure (CVP), and heart rate (HR) during hemorrhagic shock in anesthetized rabbits. Hemorrhagic hypotension of 30 mmHg was induced by rapid bleeding and was controlled by a servocontrolled pump. Following the onset of hemorrhagic hypotension, RNA response showed a triphagic pattern: an initial increase in RNA and a secondary increase followed by a profound decline in RNA. In all animals, decreases in RNA occurred within approximately 30 min after bleeding in association with significant decreases in heart rate. When RNA fell to near noise level, the effects of RA642 (0.25 mg/kg, iv, N = 10), physiological saline (N = 7), epinephrine (10 micrograms/kg, iv, N = 6), and dopamine (10 micrograms/kg, iv, N = 5) were then tested. Intravenous injection of saline produced no significant improvements of hypotension nor of reduction in RNA. However, treatment with RA642 produced a significant increase in MBP simultaneously with an increase in RNA. During the hypovolemic hypotensive phase, tachycardia did not occur after the treatment with RA642. Twenty-five minutes after the retransfusion, MBP and RNA in the RA642-treated group were at significantly higher levels than in the saline group. HR did not significantly change with the RA642 treatment after the retransfusion. In another six animals, when RNA fell to near noise level, epinephrine caused a transient increase in MBP and HR. Ventricular arrythmias occurred in 50% of epinephrine-treated animals. However, the level of MBP as improved by epinephrine was significantly lower than that by RA642 at 25 min after the retransfusion.(ABSTRACT TRUNCATED AT 250 WORDS)