Effects of long-term treatment with trandolapril on augmented vasoconstriction in rats with chronic heart failure |
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Authors: | Yoko Okumura MSc Yoshihisa Nasa PhD Atsushi Sanbe PhD Wakako Toga BSc Satoshi Takeo PhD |
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Affiliation: | aDepartment of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. |
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Abstract: | Background:Despite the clinical relevance of angiotensin I-converting enzyme (ACE)inhibitors, their effects on impaired vascular function in patients and animals with chronic heart failure (CHF) have not been fully understood. This study was undertaken to determine whether long-term treatment with an ACE inhibitor improved the altered contractile properties of vessels from rats with CHF.Methods and Results:Twelve weeks after coronary artery ligation, the rats were sacrificed and the isometric tension development of thoracic aorta, pulmonary artery, and mesenteric artery with and without endothelium was examined. Contractile responses to norepinephrine and prostaglandin F2α were augmented in endothelium-intact, but not in endothelium-denuded, thoracic aorta and pulmonary artery segments of the rat with CHF. The contractile response to angiotensin II was augmented in endothelium-denuded mesenteric artery segments of the rat with CHF, which was attenuated by indomethacin or diclofenac sodium but not by bunazosin. Trandolapril (3 mg/kg/d) was administered orally from the 2nd to 12th week after the operation. Treatment with trandolapril reversed the augmented contractile response of the rat with CHF to norepinephrine, prostaglandin F2α, and angiotensin II almost to the levels in the sham-operated rat.Conclusions:The results demonstrate that an ACE inhibitor is capable of reversing altered vascular function in the rat with CHF, suggesting that vascular beds are possible sites of action for ACE inhibitors in the therapy for CHF. |
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Keywords: | angiotensin I-converting enzyme inhibitor angiotensin norepinephrine vascular smooth muscle. |
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