Abstract
This study investigated vasoreactivity modulated by endothelium in pulmonary arteries from isolated monocrotaline (MCT)-induced pulmonary hypertensive rats. The responses to KCl, 5-hydroxytryptamine (5-HT), acetylcholine (ACh), and nitroglycerin (NTG) were studied in the pulmonary artery with and without endothelium for 3 weeks following MCT-treatment. The sensitivity of the contractile response to KCl markedly increased in the arteries with endothelium at 2 and 3 weeks after treatment, but only slightly in the arteries without endothelium. In addition, the sensitivity of the contractile response to 5-HT peaked 2 weeks after treatment in the arteries with endothelium, but at 1 week in those without endothelium. Although the removal of endothelium shifted the concentration-response curve for KCl and 5-HT to the left both in the control state and at 1 week, it did not shift the curves at 2 or 3 weeks. The relaxation responses to ACh and NTG, indicative of endothelium-dependent and independent relaxation, respectively, as well as the content of tissue cGMP were reduced 2 weeks after treatment. These results suggest that the impairment of both the endothelium-dependent and -independent relaxation responses contributes to hyperreactivity of the pulmonary artery, and may in part contribute to the development of MCT-induced pulmonary hypertension.
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