Chronic hypoxia selectively augments endothelium-dependent pulmonary arterial vasodilation

被引:75
作者
Resta, TC
Walker, BR
机构
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1996年 / 270卷 / 03期
关键词
isolated rat lungs; segmental vascular resistance; nitric oxide; hyperpolarization; endothelin; histamine; ionomycin;
D O I
10.1152/ajpheart.1996.270.3.H888
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We have previously demonstrated that chronic hypoxia (CH) augments pulmonary arterial dilation to the endothelium-derived nitric oxide (EDNO)-dependent pulmonary vasodilator arginine vasopressin (ATP). 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-{4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino] butyl} (spermine NONOate) and S-nitroso-N-acetylpenicillamine (SNAP:, in U-46619-constricted, isolated perfused lungs from control and CH rats. Additional experiments examined responses to ATP in the presence of the ET-receptor antagonist PD-145065 or the K+ channel blockers glibenclamide or tetraethylammonium (TEA) in lungs from each group. Microvascular pressure was assessed by double occlusion, allowing calculation of segmental resistances. Total and arterial vasodilatory responses to histamine, ET-1, and ionomycin were augmented in lungs from CH vs, control animals. However, CH did not alter the vasodilation to spermine NONOate or SNAP. PD-145065, glibenclamide, and TEA had no effect on responses to AVP in either group. We conclude that increased activity of arterial cNOS may be responsible for the augmented pulmonary arterial dilation to EDNO-dependent vasodilators following CH.
引用
收藏
页码:H888 / H896
页数:9
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