EFFECTS OF MATURATION, ARTERY SIZE, AND CHRONIC HYPOXIA ON 5-HT RECEPTOR-TYPE IN-OVINE CRANIAL ARTERIES

To test the hypothesis that variations in cerebrovascular reactivity t o 5-HT among arteries of different size or type, during maturation, or during acclimatization to high altitude involve differences in seroto nergic receptor subtype, we determined relative agonist potency orders and antagonist affinities in common carotid (Com), main branch middle cerebral (Main), and second branch middle cerebral (2BR) arteries fro m term fetal lambs and nonpregnant adult sheep acclimatized at sea lev el or at an altitude of 3,820 m for approximate to 110 days. In normox ic adult Com segments, agonist potency order was B-hydroxytryptamine ( 5-HT) > 5-carboxamidotryptamine (5-CT) greater than or equal to 8-hydr oxy-2(di-n-propylamino)tetraline (8-OH-DPAT); sumatriptan (Suma) produ ced no contractile response; and antagonist dissociation constant (pK( b)) values were 9.4 and 9.5 for ketanserin against 5-HT and 5-CT, 7.5 for GR-127935 against 5-HT, and 7.2 for SB-206553 against 5-HT. In nor moxic adult Main segments, agonist potency order was 5-HT > 5-CT great er than or equal to Suma greater than or equal to DPAT, and pK(b) valu es were 9.1 and 9.2 for ketanserin against 5-HT and 5-CT and 7.4 and 8 .5 for GR-127935 against 5-HT and Suma, respectively. In the 2BR segme nts from normoxic adults, agonist potency order was 5-CT > 5-HT > Suma > DPAT and pKb values were 7.4 and 7.2 for ketanserin against 5-HT an d 5-CT and 10.0 and 8.7 for GR-127935 against 5-HT and Suma, respectiv ely. Compared with normoxic adults, none of these values were signific antly different in hypoxic adults and in fetuses only the pKb values f or ketanserin against 5-HT in the 2BR segments (8.8) were greater. Fro m these results we propose that the ratio of 5-HT2 to 5-HT1 receptors is greatest in the Com and decreases progressively to its smallest val ues in 2BR or smaller segments. Because this gradient appears stable a nd relatively resistant to the effects of maturation and chronic hypox ia, changes in reactivity associated with these perturbations may invo lve alterations in receptor density and/or coupling efficiency for 5-H T in ovine cranial arteries.