title: Does combined therapy of Ca-channel blocker and angiotensin converting enzyme inhibitor exceed monotherapy in renal protection against hypertensive injury in rats?
abstract: Either calcium channel blocker (CCB) or angiotensin converting enzyme inhibitor (ACEi) is used as an antihypertensive agent, and we are recommended to use them in combination to refractory hypertension with evidence dependent on clinical observations. We examined the renal protective effect of the combined therapy with calcium channel blocker (amlodipine) and angiotensin converting enzyme inhibitor (enalapril) against hypertensive renal injury in 5/6 nephrectomized spontaneously hypertensive rats (SHRs) with salt loading, comparing with monotherapy of each drug. Forty males SHRs with 5/6 nephrectomy and salt loading were divided to five groups: group 1 as control (n = 8), group 2 received 0.2 mg/kg/day of amlodipine (n = 8), group 3 received 0.2 mg/kg/day of enalapril (n = 8), group 4 (n = 8) and group 5 (n = 8) that were treated with 0.1 mg/kg/day and 0.2 mg/kg/day of each drug in combination respectively. Either amlodipine or enalapril had remarkable effects on reducing the increases in blood pressure and urinary protein excretion. In histopathological examination, it also suppressed renal injury significantly. Additional significant effect of combined therapy was not observed in blood pressure and urinary protein. There were not remarkable, additional effects of the combination of CCB and ACEi on protecting the remnant kidney in 5/6 nephrectomized SHRs fed a high-salt diet, possibly because sodium retention was not alleviated by the combination.
authors.affiliation: Department of Internal Medicine, Keio University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kanno
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Ikenaga
authors.forename: N
authors.initials: N
authors.lastname: Ishii
authors.forename: H
authors.initials: H
authors.lastname: Itoh
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D017311:Amlodipine / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004231:Diuresis / Q000187:drug effects; D004338:Drug Combinations; D004656:Enalapril / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D017311:Amlodipine; D004656:Enalapril