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 hypotension, and arterial hypercapnia in cerebral arterioles of anesthetized cats equipped with cranial windows for the observation of the cerebral microcirculation. The allosteric modifiers of hemoglobin are isomers of 2-(aryloxy)-2-methylpropionic acid. They shift the oxygen dissociation of hemoglobin to the right, thereby facilitating the local release of oxygen. When these compounds were applied topically by superfusion 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 significantly the vasodilation from arterial hypoxia and arterial hypotension. They did not influence the vasodilation from arterial hypercapnia. Spectrophotometric measurements of optical densities from pial veins 50-80 microns in diameter indicated that the superfusion with the allosteric 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 useful as tools in investigating oxygen-dependent mechanisms.
Wei
E P
EP
Departments of Medicine and Medicinal Chemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Randad
R S
RS
Levasseur
J E
JE
Abraham
D J
DJ
Kontos
H A
HA
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004976:Ethacrynic Acid / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism*; D007022:Hypotension / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007536:Isomerism; D010100:Oxygen / Q000097:blood*; D011422:Propionates / Q000494:pharmacology; D014664:Vasodilation
D006454:Hemoglobins; D011422:Propionates; D004976:Ethacrynic Acid; D010100:Oxygen