A comparative study of the effects of alpha 1-adrenoceptor antagonists on sympathetic function in rats

alpha 1-Adrenoceptor antagonists were comparatively evaluated in terms of their acute and long-term effects on sympathetic function in rats. In the first study, the effects of alpha 1-adrenoceptor antagonists on cardiovascular sympathetic nerve activity were electrophysiologically determined in anesthetized normotensive rats. Intravenous administration of four alpha 1-antagonists-prazosin, bunazosin, SM-2470, and YM-617-produced no changes or decreases in heart rate, in spite of the expected reflex tachycardia resulting from their marked hypotensive effect. Among the alpha 1-antagonists examined, some also produced a significant decrease in inferior cardiac nerve activity. All except prazosin decreased renal nerve activity, while prazosin showed an opposite tendency to increase the renal nerve activity. On the other hand, preganglionic adrenal nerve activity, an index of central sympathoinhibitory activity, underwent a significant decrease after SM-2470 and YM-617 administration, and a dose-dependent increase was observed in response to prazosin and bunazosin. In the second study, the long-term (4 weeks) effects of alpha 1-antagonists on plasma and urinary catecholamine levels and urinary electrolyte excretions were evaluated in stroke-prone spontaneously hypertensive rats (SHRSP). Prazosin and bunazosin did not exert any consistent changes on plasma and urinary catecholamine concentrations. SM-2470, however, significantly decreased both plasma and urinary epinephrine concentrations. In addition, bunazosin and SM-2470 produced increases in urinary sodium and potassium excretions. Urine volume tended to increase after bunazosin administration. Prazosin, on the other hand, produced decreases in urinary sodium and potassium excretions as well as in urine volume. These findings demonstrate that alpha 1-antagonists differentially affected cardiovascular sympathetic tone in anesthetized rats. These varied sympathoinhibitory profiles might be in part explainable as different effects on urinary electrolyte metabolism after long-term administration of alpha 1-antagonists in SHRSP.