EFFECT OF LOCAL CHANGE IN O2 SATURATION OF HEMOGLOBIN ON CEREBRAL VASODILATION FROM HYPOXIA AND HYPOTENSION

We tested the effect of certain newly synthesized allosteric modifiers of hemoglobin on the dilation induced by arterial hypoxia, arterial h ypotension, and arterial hypercapnia in cerebral arterioles of anesthe tized cats equipped with cranial windows for the observation of the ce rebral microcirculation. The allosteric modifiers of hemoglobin are is omers of 2-(aryloxy)-2-methylpropionic acid. They shift the oxygen dis sociation of hemoglobin to the right, thereby facilitating the local r elease of oxygen. When these compounds were applied topically by super fusion at a rate of 1 ml/min in a concentration of 0.1 mM, they had no significant effect on baseline arteriolar diameter but reduced signif icantly the vasodilation from arterial hypoxia and arterial hypotensio n. They did not influence the vasodilation from arterial hypercapnia. Spectrophotometric measurements of optical densities from pial veins 5 0-80 mum in diameter indicated that the superfusion with the allosteri c compounds reduced hemoglobin oxygen saturation both during room air breathing and during hypoxia. We conclude that the vasodilations from arterial hypoxia and arterial hypotension are mediated by local oxygen -dependent mechanisms. The allosteric modifiers of hemoglobin may be u seful as tools in investigating oxygen-dependent mechanisms.