Beneficial Effects of Trandolapril in Uninephrectomized Spontaneously Hypertensive Rats: Role of Cyclooxygenase Pathway

Abstract

Abstract:The antihypertensive efficacy of the angiotensin-converting enzyme inhibitor trandolapril was evaluated in uninephrectomized spontaneously hypertensive rats. After 5 weeks of treatment, blood pressure, cardiac and aortic mass, as well as the functional status of the aortic endothelium, and the role played by the cyclooxygenase pathway were investigated. In addition, the effect of a sub-antihypertensive dose of the calcium antagonist verapamil, in combination with trandolapril, was also investigated. As compared to placebo, trandolapril returned blood pressure and aortic lamina media cross sectional area to normotensive values, significantly reduced the heart-to-body weight, and improved the acetylcholine-induced relaxation of aortic rings. This latter effect is thought to be mediated by the elimination of a substance derived from the cyclooxygenase pathway. Verapamil, in single therapy, did not reduce blood pressure, or heart-to-body weight, increased aortic lamina media cross sectional area and impaired acetylcholine-induced relaxation. When combined with trandolapril in dual therapy, some of the beneficial effects of trandolapril remained, whereas others were counterbalanced by verapamil. In conclusion, trandolapril proved to be an effective therapeutic drug in this animal model of hypertension. Combination of trandolapril with a sub-antihypertensive dose of verapamil did not show any positive synergistic effect; on the contrary, it outweighed some of the beneficial effects of trandolapril.