EFFECT OF THE H-1 BLOCKER D-CHLORPHENIRAMINE ON CEREBRAL BLOOD-FLOW IN THE CONSCIOUS DOG DURING NORMOCAPNIC HYPOXIA

The mechanism causing cerebral vasodilatation during hypoxia remains u nclear. A role for histamine is suspected because H-2 receptor-blockin g drugs blunt the hypoxia-induced increase in cerebral blood flow (CBF ). Moreover, in vitro blockade of H-1 receptors by chlorpheniramine de creases the vasodilatation of cerebral arteries that is induced by his tamine. The present study tested the hypothesis that an H-1 receptor b locker (d-chlorpheniramine) would have a similar effect in vivo during hypoxia. Isocapnic hypoxia (inspired oxygen fraction, FIO2 = 0.10; in spired carbon dioxide fraction, FICO2 = 0.035) was induced in 16 consc ious dogs randomly divided into two groups: eight dogs received saline intravenously (controls) at time 0 (normoxia) and after 2 h and 4 h h ypoxia, and the other eight dogs received d-chlorpheniramine intraveno usly (0.5 mg kg(-1)) to block the H-1 receptors. Regional CBF was meas ured by the radioactive microspheres technique 15 min after each injec tion of d-chlorpheniramine or saline. In the control group, CBF increa sed during hypoxia in all regions of the brain. In the d-chlorpheniram ine group, total CBF increased similarly after 2 h of hypoxia. After 4 h of hypoxia, the increase was limited, especially in the pens, cereb ral peduncles, hippocampus, hypothalamus, thalamus, and occipital lobe s (six out of 12 studied regions). It is concluded that the H-1 blocke r d-chlorpheniramine did not strongly inhibit the increase in CBF duri ng hypoxia. After cumulative doses, however, as in the fourth hour of hypoxia, the increase in total CBF was limited.