title: Renal protective effects of efonidipine in partially nephrectomized spontaneously hypertensive rats.
abstract: We investigated the effects of a calcium antagonist, efonidipine, which was reported to dilate not only afferent arterioles but also efferent alterioles, on progression of renal failure in salt-loaded partially nephrectomized spontaneously hypertensive rats (SHR). Forty-four SHR's with 5 of 6 nephrectomy were divided into four groups: group 1 as control (n=20); group 2, efonidipine-treated (n=8); group 3, enalapril-treated (n=8); and group 4, nifedipine-treated (n=8). The rats were given these drugs and a high-salt diet (5% NaCl) for 8 weeks. During the experiment, systolic blood pressure (SBP) and daily urinary protein excretion were measured every 2 weeks. At the end of the study, serum creatinine was determined, and renal tissues were obtained for light microscopic examination. SBP was markedly reduced by 8-week antihypertensive treatment. (control, 267+/-7 mmHg; efonidipine, 181+/-7 mmHg; enalapril, 200+/-12 mmHg; nifedipine, 184+/-6 mmHg). Glomerular sclerosis developed markedly in the control group, but was partially prevented in all treated groups. Similarly, urinary protein excretion (UPE) was suppressed by efonidipine (180+/-16 mg/day) and enalapril (186+/-16 mg/day vs. 301+/-28 mg/day for control). In contrast, nifedipine failed to prevent the increase in urinary protein excretion (258+/-22 mg/day). In conclusion, efonidipine attenuates SBP increase and ameliorates glomerular injury as well as nifedipine and enalapril. Furthermore, beneficial effects of efonidipine, but not nifedipine, on proteinuria suggest that different mechanisms mediate the improvement of proteinuria; one possible mechanism could be efferent arteriolar dilation, not reported in nifedipine.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Y
authors.initials: Y
authors.lastname: Kanno
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Takenaka
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D018450:Disease Progression; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology* / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D013599:Systole
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine