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 (felodipine) and an angiotensin-converting enzyme (ACE) inhibitor (enalapril), alone or in combination, 10 groups of 19-week-old spontaneously hypertensive rats (SHR) (with or without N(G)-nitro-L-arginine methyl ester [L-NAME]) were studied using renal micropuncture techniques. Group 1 (control), group 2 (felodipine, 30 mg x kg(-1) x d[-1]), group 3 (enalapril, 30 mg x kg(-1) x d[-1]), and group 4 (felodipine plus enalapril, 15 mg x kg(-1) x d(-1) each agent) were studied after 3 weeks of treatment without 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 felodipine plus enalapril, respectively, for the subsequent 3 weeks. All three treatments resulted in reductions in mean arterial pressure and total peripheral vascular resistance (P<.001) that were associated with important structural and functional renal microcirculatory improvements. Thus, the pathological nephrosclerosis (subcapsular and juxtamedullary) glomerular and arteriolar injury scores were improved (P<.05 at least) in association with normalization of afferent and efferent arteriolar resistances, and single-nephron glomerular filtration rate, plasma flow, and blood flow were significantly improved, as well as the ultrafiltration coefficient (compared with group 5, L-NAME). Thus, the calcium antagonist felodipine, alone or in combination with an ACE inhibitor, not only prevented but also reversed L-NAME-exacerbated hypertensive nephrosclerosis in SHR.
Francischetti
A
A
Alton Ochsner Medical Foundation, New Orleans, La 70121, USA.
Ono
H
H
Frohlich
E D
ED
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D015736:Felodipine / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D004656:Enalapril; D015736:Felodipine; D019331:NG-Nitroarginine Methyl Ester