Chronic hypoxia selectively augments endothelium-dependent pulmonary arterial vasodilation

We have previously demonstrated that chronic hypoxia (CH) augments pulmonary arterial dilation to the endothelium-derived nitric oxide (EDNO)-dependent pulmonary vasodilator arginine vasopressin (AVP). The present study examined 1) whether this enhanced vasoreactivity is observed with other agents that act by stimulating constitutive NO synthase (cNOS), 2) whether CH increases arterial vascular smooth muscle sensitivity to NO, and 3) whether endogenous endothelin (ET) or an endothelium-derived hyperpolarizing factor (EDHF) contributes to this altered arterial reactivity following CH. We examined responses to the receptor-mediated EDNO-dependent dilators histamine and ET-1, the nonreceptor-mediated EDNO-dependent dilator ionomycin, and the NO donors 1, 3-propanediamine, N- inverted question mark4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino] butyl inverted question mark (spermine NONOate) and S-nitroso-N-acetylpenicillamine (SNAP) in U-46619-constricted, isolated perfused lungs from control and CH rats....