Comparison of the effects of indapamide and captopril on the development of spontaneous hypertension.

OBJECTIVES

The effects of indapamide, a thiazide-like diuretic, and captopril, an angiotensin-converting enzyme inhibitor, on spontaneous hypertension and the development of left ventricular hypertrophy (LVH), nitric oxide generation and oxidant status were investigated.

METHODS

Six-week-old male spontaneously hypertensive rats (SHR) were treated with indapamide (1 mg/kg per day) or captopril (10 mg/kg per day) or a combination of indapamide plus captopril. After the 6-week treatment, nitric oxide synthase (NOS) activity, the expression of NOS isoform proteins, conjugated dienes concentration and relaxation responses of the femoral artery were analyzed.

RESULTS

Indapamide and captopril partly prevented a blood pressure increase in young SHR. Captopril in contrast to indapamide reduced LVH. The effect of the combined indapamide and captopril treatment on the prevention of hypertension was additive. Combined indapamide and captopril treatment increased NOS activity and endothelial NOS protein expression in the aorta and decreased conjugated dienes concentration in the kidney compared with the indapamide monotherapy group. Indapamide and indapamide and captopril treatment increased acetylcholine-induced relaxation of the femoral artery.

CONCLUSION

Whereas captopril reduced LVH, indapamide enhanced NOS activity and decreased oxidative damage in the case of the combined treatment. It is concluded that the complex protective effects of the combined indapamide plus captopril treatment on hypertension may be exerted via its effects on blood pressure, hypertrophy and vasorelaxation.