THE RENIN-ANGIOTENSIN SYSTEM IN THE TYPE-II DIABETIC OBESE ZUCKER RAT

Recently, the obese Zucker rat (OZR), an animal model of non-insulin-d ependent (type II) diabetes, was shown to respond to converting enzyme inhibition with decreased albuminuria and a marked attenuation of glo merular injury. It was hypothesized that the OZR would possess low pla sma renin values and an increased vascular responsiveness to angiotens in II, and therefore, the renin-angiotensin system (PRA, active renin, inactive renin, renal renin content, and plasma angiotensinogen) and vascular reactivity in OZR at 10 and 24 wk of age were investigated. P RA and renin concentration, inactive plasma renin, and renal renin con tent were all significantly (P < 0.05) reduced in OZR when compared wi th age-matched lean controls. The ratio of inactive to total renin was significantly increased in the OZR. OZR aortic ring vascular reactivi ty to KCl, norepinephrine, and angiotensin II was assessed. Despite es sentially equal or increased contractile responses to KCI and norepine phrine at both 10 and 24 wk of age, the OZR was not more sensitive to angiotensin II and displayed a significantly reduced contractile respo nse to angiotensin II at 24 wk of age, when compared with lean age-mat ched controls. It was concluded that the renal protective effect of co nverting enzyme inhibition in OZR, despite significantly reduced PRA a nd concentration, inactive plasma renin, and renal renin content, may not be due to a diabetes-induced increased vascular reactivity to angi otensin II.