RENOPROTECTIVE EFFECTS OF FELODIPINE AND OR ENALAPRIL IN SPONTANEOUSLY HYPERTENSIVE RATS WITH AND WITHOUT L-NAME/

To determine the renoprotective effects of a calcium antagonist (felod ipine) and an angiotensin-converting enzyme (ACE) inhibitor (enalapril ), alone or in combination, 10 groups of 19-week-old spontaneously hyp ertensive rats (SHR) (with or without N-G-nitro-L-arginine methyl eate r [L-NAME]) were studied using renal micropuncture techniques. Group 1 (control), group 2 (felodipine, 30 mg.kg(-1).d(-1)), group 3 (enalapr il, 30 mg.kg(-1).d(-1)), and group 4 (felodipine plus enalapril, 15 mg .kg(-1).d(-1) each agent) were studied after 3 weeks of treatment with out L-NAME. L-NAME (50 mg/L) cotreatment was administered in drinking water to groups 6 through 10 using the same doses of each agent as in groups 1 through 4: group 5 (only L-NAME), group 6 (felodipine), group 7 (enalapril), and group 8 (felodipine plus enalapril). Groups 9 and 10 received L-NAME initially for 3 weeks followed by felodipine or fel odipine plus enalapril, respectively, for the subsequent 3 weeks. AU t hree treatments resulted in reductions in mean arterial pressure and t otal peripheral vascular resistance (P<.001) that were associated with important structural and functional renal microcirculatory improvemen ts. Thus, the pathological nephrosclerosis (subcapsular and juxtamedul lary) glomerular and arteriolar injury scores were improved (P<.05 at least) in association with normalization of afferent and efferent arte riolar resistances, and single-nephron glomerular filtration rate, pla sma now, and blood now were significantly improved, as well as the ult rafiltration coefficient (compared with group 5, L-NAME). Thus, the ca lcium antagonist felodipine, alone or in combination with an ACE, inhi bitor, not only prevented but also reversed L-NAME-exacerbated hyperte nsive nephrosclerosis in SHR.