Renal vasodilatory influence of endogenous carbon monoxide in chronically hypoxic rats

Chronic hypoxia (CH) attenuates systemic vasoconstriction to a variety of a gonists in conscious rats. Recent evidence suggests that similarly diminish ed responses to vasoconstrictors in aortic rings from CH rats may be due to increased endothelial heme oxygenase (HO) activity and enhanced production of the vasodilator carbon monoxide (CO). Thus we hypothesized that a hypox ia-induced increase in HO activity is responsible for decreased vasoconstri ctor responsiveness observed in conscious CH rats. CH (4 wk at 0.5 atm) and control rats were renal denervated and instrumented for the measurement of renal blood flow (RBF) and blood pressure. First, renal vasoconstrictor re sponses to graded intravenous infusion of phenylephrine (PE) were assessed in conscious rats. CH rats demonstrated significantly diminished renal vaso constrictor responses to PE compared with control responses that persisted even with acute restoration of normoxia. In additional experiments, CH rats exhibited increased renal vascular resistance and decreased RBF in respons e to the HO inhibitor zinc protoporphyrin IX (11 mu mol/kg iv), whereas ren al hemodynamics were unaffected by the inhibitor in control animals. Furthe rmore, we demonstrated greater HO enzyme activity in renal tissue from CH r ats compared with controls. These data suggest that enhanced HO activity co ntributes a tonic vasodilatory influence in the renal vasculature of CH rat s that may be responsible for the diminished sensitivity to vasoconstrictor agonists observed under these conditions.