ENDOTHELIAL DYSFUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS - CONSEQUENCES OF CHRONIC TREATMENT WITH LOSARTAN OR CAPTOPRIL

Background Hypertension is associated with endothelial dysfunction cha racterized by decreased endothelium-dependent relaxations and increase d endothelium-dependent contractions. Angiotensin converting enzyme in hibitors and thromboxane A(2) receptor antagonists decreased the endot helium dysfunction in hypertensive animals, Objective To investigate t he effects of prolonged treatment with losartan on endothelium-depende nt and -independent relaxations and contractions in aortic rings from spontaneously hypertensive rats (SHR). Materials and methods Male SHR aged 16 weeks were treated for 12 consecutive weeks either with 10 mg/ kg losartan per day or with 60 mg/kg captopril per day administered vi a their drinking water, The systolic blood pressure was evaluated basa lly and during week 12. At the end of the treatment period, the vascul ar reactivity in aortic rings was studied, A group of rats treated wit h captopril was studied as a reference group. Results Losartan and cap topril reduced the blood pressure significantly and comparably. Both d rugs enhanced acetylcholine-induced relaxations and reduced the maxima l contractile response to acetylcholine in the presence of N-G-nitro-L arginine methyl ester (1-NAME). Contractile responses to phenylephrin e, endothelin-l and U46619 were not affected by these treatments, Incr eased relaxing responses to superoxide dismutase were observed only in captopril-treated rats. Losartan reduced the contractile response to angiotensin II. By contrast, this contractile response was elevated in rats treated with captopril, Conclusions Prolonged antihypertensive t reatments with losartan and captopril decreased the endothelial dysfun ction in aortic rings from SHR not only by enhancing NO-dependent rela xations but also by reducing the contractions in response to an endoth elium-derived contracting factor, The results further confirm that an endothelium-derived contracting factor plays a role in vascular dysfun ction in SHR and the relationships between this factor and angiotensin II.