CAPTOPRIL INCREASES NOREPINEPHRINE SPILLOVER RATE IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS

These experiments were designed to test the hypothesis that the antihypertensive action of the converting enzyme inhibitor captopril in conscious spontaneously hypertensive rats is associated with an inhibition of norepinephrine release from peripheral sympathetic neurons. Radiotracer techniques were used to measure norepinephrine clearance and spillover rate into plasma. A single 30 mg/kg (s.c.) dose of captopril elevated norepinephrine spillover rate by 20 to 25 and 45 to 60% at 0.5- and 2-hr postinjection, respectively. At 2-hr postinjection, captopril (10 and 30 mg/kg s.c.) produced a dose-related fall in mean arterial pressure (MAP) and dose-related increase in norepinephrine spillover rate. The 30-mg/kg dose was more effective in decreasing MAP when given s.c. as compared to i.v. dosing. When equivasodepressor doses of captopril, hydralazine and prazosin were compared at 2-hr postinjection, the increases in norepinephrine spillover rate produced by captopril (44%) and hydralazine (68%) were not different. However, prazosin elevated norepinephrine spillover rate by 137%. Norepinephrine clearance was not altered by captopril. When MAP was lowered to the same extent (-17 to -23%) by 5 days of continuous treatment with captopril, enalaprilat and minoxidil, the increases in norepinephrine spillover rate (50-65%) were not different in the three treatment groups. In conclusion, these data do not support the hypothesis that captopril lowers blood pressure by inhibiting the neuronal release of norepinephrine.