Discordant effects of an angiotensin converting enzyme inhibitor (ACEI) vs an AII receptor antagonist (AA) on blood pressure and renal damage in spontaneously hypertensive rats (SHR).

Studies of ACEIʹs suggest that blockade of the renin-AII system prevents kidney damage, however, ACEI have effects in addition to reducing AII levels. AAʹs block the system selectively, but few studies have examined the effects of AA on renal disease. SHR that underwent uninephrectomy at 5 weeks of age were untreated (CON); given enalapril (ENP); the AA, irbesartan (IB); or IB plus a low (0.9%) sodium diet (IBLS). Systolic blood pressure (SBP) and proteinuria (PROT) were monitored. At 7 months, mean arterial pressure (MAP), inulin clearance (GFR), kidney weight and the extent of glomerular and interstitial injury were assessed. SBP was reduced by treatment, but was higher in IB than in ENP or IBLS. Increasing the dose of IB by more than 10 fold did not reduce SBP further. Results at 7 months include (Mean±SE): Kidney weights did not differ, however, micropuncture studies revealed that IB significantly reduced glomerular pressure. Thus, ACEI have AII independent actions and reduce blood pressure and proteinuria more effectively than AA in SHR. Salt restriction potentiates the beneficial effects of AA. Both ENP and IB prevented morphologic damage to the same extent, suggesting that the drugs have important, intrarenal effects that are not well correlated with systemic blood pressure or protein excretion rate.