Meclofenamate potentiates vasoreactivity to alpha-adrenergic stimulation in chronically hypoxic guinea pigs

The aim of this study was to examine the effect of chronic hypoxia on systemic vascular reactivity and the role of prostaglandins in modulating the vascular response to chronic hypoxia. Meclofenamate, a prostaglandin synthesis inhibitor, increased the systemic vascular resistance response to the alpha-adrenergic agonist, phenylephrine, in awake, unrestrained guinea pigs exposed for 6 wk to high altitude (3,900 m), but it did not alter the response in animals kept at low altitude (1,600 m). The systemic vascular resistance response to phenylephrine before treatment with meclofenamate was the same in high- and low-altitude animals. Meclofenamate also increased the contractile response to phenylephrine in aortic rings isolated from high- but not low-altitude animals. The systemic vascular resistance response to angiotensin II was the same in high- and low-altitude animals, and meclofenamate increased this response to the same extent in both groups. Thus chronic hypoxia appeared to enhance vascular production of dilator prostaglandins during beta-adrenergic stimulation.