Effects of angiotensin II type 1 receptor antagonist on nitric oxide synthase expression and myocardial remodeling in goldblatt hypertensive rats

We evaluated the effects of long-term treatment with TCV-116, an angiotensi n II type 1 receptor antagonist, on endothelial-cell nitric oxide synthase (eNOS) messenger RNA (mRNA) and protein expression in the left ventricle an d its relation to myocardial remodeling in Goldblatt hypertensive rats. Two -kidney, one-clip Goldblatt hypertensive rats (RHR) were assigned either to a TCV-116 treatment group (RHR-TCV, n = 8, 3 mg/kg/day, subdepressor dose) or to a group without treatment (RHR-V, n = 7) after their kidneys had bee n clipped for 4 weeks. TCV-116 was administered to rats in the treatment gr oup for 6 weeks, and age-matched sham-operated rats (ShC, n = 7) served as a control group. Blood pressure in RHR-V and RHR-TCV was similar and signif icantly higher than that in ShC. The eNOS mRNA and protein levels and NOS a ctivity in the left ventricle was significantly decreased in RHR-V compared with ShC, and significantly increased in RHR-TCV compared with ShC and RHR -V, RHR-V demonstrated a significant increase in fibrosis factor (type I co llagen) mRNA expression, perivascular fibrosis, and myocardial fibrosis. Th ese parameters in the microvasculature were improved significantly by TCV-1 16. Subdepressor dose of TCV-116 improved pathological myocardial changes i n RHR, which may be due in part to an increased eNOS mRNA and protein expre ssion and NOS activity in the left ventricle.