Multiple defects in the renin-angiotensin system in alloxan-diabetic kidney.
A defect in the renin-angiotensin system has been shown in diabetic patients and experimental animals, in particular with nephropathy or autonomic neuropathy. The mechanism for this low plasma renin activity (PRA) is poorly understood. In order to clarify this defect, the renin-angiotensin system was studied in alloxan-induced diabetic and age-match control mice. In diabetic animals, kidney renin activity (KRA) was significantly lower than that of the controls, while plasma renin substrate (PRS) concentration was slightly higher and PRA was normal. The amount of injected radiolabeled renin extracted by the kidney was normal, but the amount extracted by the liver was significantly decreased in diabetic animals. On the other hand, the degradation of the extracted renin by both the kidney and the liver was elevated as compared to the controls. This high degradation rate was accompanied by a slight increase in lysosomal protease activity in the kidneys. In in vivo studies, isoproterenol-induced PRA was 20-fold in control animals. In diabetics, isoproterenol-induced PRA was attenuated and rose only four- to fivefold over basal level. The angiotensin converting enzyme (ACE) activity in the kidney was significantly decreased in the diabetic state. It is concluded that there were multiple defects in the renin-angiotensin system in this diabetic model, namely, a depletion of renin storage with subsequent loss of maximal responsiveness to the adrenergic agonist in renin release, an elevation of intrarenal renin degradation together with a deficiency in ACE which would possibly lead to a decrease in intrarenal formation of angiotensin II.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012083:Renin / Q000097:blood / Q000378:metabolism; D012084:Renin-Angiotensin System
D001786:Blood Glucose; D012083:Renin; D007545:Isoproterenol