Aims: 

We compared the effects of different antihypertensive agents, thiazide-like diuretic (indapamide) and angiotensin-converting enzyme inhibitor (captopril) on the development of spontaneous hypertension. The combined effect of these agents was analyzed particularly. Methods:

Six-week-old male SHR were treated with indapamide (1 mg/kg/day) or captopril (10 mg/kg/day) or with indapamide+captopril combination. After 6-week-treatment, nitric oxide synthase (NOS) activity, endothelial (eNOS) and neuronal (nNOS) protein expressions, and concentration of conjugated dienes (CD), a marker of oxidative damage, were determined in the left ventricle, aorta and kidney.

Results: 

Indapamide (I), captopril (C) and I+C treatment significantly decreased blood pressure in young SHR. Indapamide, in contrast to captopril, increased NOS activity, as well as eNOS expression in the aorta and attenuated CD concentration in the kidney. I+C combined treatment increased NOS activity as well as eNOS expression and decreased CD concentration comparably to indapamide alone treated group. Moreover, indapamide, captopril, and I+C treatment increased nNOS expression in the left ventricle. Indapamide significantly increased acetylcholine-induced relaxations of the femoral artery. Captopril failed to affect these relaxations and simultaneous I+C treatment increased the relaxations similarly as indapamide alone

Conclusion: 

Indapamide treatment along with captopril had the additive effect on the prevention of blood pressure increase. On the other hand, this combination increased NOS activity, as well as eNOS expression in the aorta, similarly as indapamide alone. Our results suggested that indapamide is responsible for NOS activity and eNOS expression increase after the combined treatment. This effect of indapamide may contribute to its vasorelaxant and antihypertensive properties.