개의 신장기능에 미치는 Guanabenz의 영향

Effects of Guanabenz on Renal Function in Dog

In this study attempts were made to observe the effects of guanabenz on renal function in dog, which manifests the antihypertensive action by inhibition of sympathetic tone through stimulating the presynaptic adrenoceptor (alpha2-adrenoceptor). Guanabenz, when injected at a dose of 30.0mcg/kg, or infused at a dose of 3.0mcg/kg/min intravenously, produced diuretic action with increased amounts of Na+ and K+ in urine, and with decreased reabsorption rates of Na+ and K+ in renal tubules. It was also observed that the rates of osmolar and free water clearances were increased, but the glomerular filtration rate and renal plasma flow were not changed. Guanabenz injected at a dose of 3.0mcg/kg into a carotid artery or infused intravenously at a dose of 3.0mcg/kg/min in a state of water diuresis elicited the diuretic action of the similar aspect as a case of guanabenz given intravenously. The diuretic action produced by guanabenz was completely blocked by pretreatment of i.v. prazosin, alpha1-adrenoblocking agent, or of i.v. yohimbine, alpha2-adrenergic blocking agent. Prazosin, when given into a renal artery, inhibited the diuretic action by i.v. guanabenz in only injected kidney, whereas in case of yohimbine the action was inhibited in both kidney. Guanabenz infused at a dose of 1.0mcg/kg/min into a renal artery exhibited no significant changes of renal function in both kidney. In denervation experiments, guanabenz given intravenously produced typical diuretic action in innervated kidney, whereas in denervated kidney, it did not affect the action at initial period but exhibited the action with increase of only free water clearance at later period. These results suggest that guanabenz produced diuretic action in dog by inhibition of electrolyte reabsorption rates in renal tabules, mainly proximal tubule and of ADH release, which is mediated by stimulating of central sympathetic alpha2-receptor.