ENHANCED PULMONARY ARTERIAL DILATION TO ARGININE-VASOPRESSIN IN CHRONICALLY HYPOXIC RATS

Chronic hypoxic exposure elicits pulmonary vascular remodeling and may alter normal pulmonary endothelial function. We examined the vasodila tory response to the receptor-mediated endothelium-dependent dilator a rginine vasopressin (AVP), the nonreceptor-mediated endothelium-depend ent dilator A-23187, and the nitric oxide (NO) donor sodium nitropruss ide in lungs isolated from control or chronically hypoxic rats. Lungs were isolated from male Sprague-Dawley rats and perfused with a physio logical saline solution containing 4% albumin. Arterial and venous pre ssures were monitored and microvascular pressure was estimated by doub le occlusion, allowing assessment of segmental resistances. After equi libration, lungs were constricted with the thromboxane mimetic U-46619 . Upon development of a stable presser response, lungs were dilated wi th one of the above agents. A series of doses of AVP was administered to separate groups of lungs from control or chronically hypoxic rats. Lungs from chronically hypoxic rats exhibited an augmented dilatory re sponse to AVP compared with control lungs, and this effect was due to enhanced dilation of precapillary segments. The total and segmental va sodilatory responses to A-23187 and sodium nitroprusside were not diff erent between the two groups of lungs, suggesting that chronic hypoxia did not upregulate the enzyme NO synthase or enhance the vascular smo oth muscle responsiveness to NO. Thus our data suggest that the augmen ted total and pulmonary arterial dilation to AVP after chronic hypoxia is most likely due to altered receptor-mediated processes of the horm one.