Korean Journal of Nephrology 1992;11(2):89-100.

당뇨성 신장질환의 발생기전에 관여하는 Renin - Angiotensin 계의 역할

하헌주 , 우호철 , 김경환

Abstract

Diabetic nephropathy, a microvascular complication, is still a hallmark of diabetes mellitus. Although the etiology of diabetic nephropathy remains to be elucidat- ed, previous study suggested that renal vascular struc- tural changes could not be sole pathogenesis for de- creased renal blood flow in streptozotocin-induced dia- betic rats (STZR). Basal values of total renal blood flow (using an electromagnetic fiowmeter), mean arterial pressure and renal vascular resistance of secobarbital- anesthetized STZR (n=10) and age-matched control rats (CR; n=9) were 6.1+0.4 vs. 7.5±0.5ml/min/g kidney weight (p<0.05), 118±3 vs. 114±3mmHg, and 20.1±1.4 vs. 15.6±0.9 mmHg/ml/min/g kidney weight (p<0.01), respectively. This study evaluated the participation of renin-angiotensin system on increased renal vasoconstriction in STZR by determining the reactivity to exogenously administered angiotensins and by determining the effect of captopril on renal vascular tone. Elicited renal vasoconstriction in response to intravenously administered angiotensin I (50-200 ng/ kg) or angiotensin II (4-128 ng/kg) under the presence or absence of endogenous converting enzyme, respec- tively, were quite similar between two groups. Captopril at 0.5 mg/kg followed by 10 pg/kg/min produced simi- lar degree of renal vasodilation between STZR and CR, thus, did not normalize higher baseline resistance in STZR kidneys. In addition, chronic administration of captopril (100 mg/1 of drinking water) did ameliorate microalbuminuria but not renal hypoperfusion associat- ed with diabetes. Electron microscopic obseravation revealed that only proximal tubules, not glomeruli, of STZR were affected. The microvilli which involves in protein reabsorption were reduced in STZR and chronic administration of captopril prevented it. Taken together, the data suggest that I) other factors than renin-angiotensin system may play a role in renal vasoconstriction of short-term diabetic STZR, ii) amelioration of microalbuminuria by captopril do not result from the effect on renal hemodynamics but from an improvement of renal function.