Benazepril combined with either amlodipine or hydrochlorothiazide is more effective than monotherapy for blood pressure control and prevention of end-organ injury in hypertensive Dahl rats.
We studied the effect of hydrochlorothiazide (HCTZ), the angiotensin-converting enzyme inhibitor benazepril, the calcium channel blocker amlodipine, or a combination of benazepril/amlodipine or benazepril/HCTZ on systolic blood pressure (BP) and end-organ injury (left ventricular hypertrophy, proteinuria, and endothelium-dependent relaxation to acetylcholine) in hypertensive Dahl salt-sensitive rats fed either a normal-salt (0.5% NaCl) or high-salt (4% NaCl) diet for 6 weeks. Rats fed a high-salt diet developed hypertension and significant end-organ injury. Monotherapy with HCTZ (75 mg/L in drinking water) or amlodipine (10 mg/kg/day by gavage) reduced systolic BP and proteinuria; benazepril (40 mg/kg/day by gavage) decreased proteinuria without significantly lowering systolic BP. In rats receiving a high-salt diet, only HCTZ reduced left ventricular hypertrophy, whereas endothelium-dependent relaxation was improved by amlodipine and benazepril but not by HCTZ. Combining benazepril with either amlodipine or HCTZ dramatically reduced systolic BP and end-organ injury. These data clearly support clinical studies suggesting that combination therapy is more effective than monotherapy for systolic BP control and prevention of end-organ injury. Complementary mechanisms of action of agents from different antihypertensive classes appear to facilitate the greater benefit on BP and end-organ injury.
Zhou
Ming-Sheng
MS
Nephrology Section, VA Medical Center, Renal Division, Miller School of Medicine, and Vascular Biology Institute, University of Miami, Miami, Florida, USA.
Jaimes
Edgar A
EA
Raij
Leopoldo
L
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001552:Benzazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000633:toxicity; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D001552:Benzazepines; D017673:Sodium Chloride, Dietary; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000109:Acetylcholine; C044946:benazepril