NE-INDUCED CONTRACTION, ALPHA(1)-ADRENERGIC RECEPTORS, AND INS(1,4,5)P-3 RESPONSES IN CEREBRAL-ARTERIES

Adrenergic-mediated responses in cerebral vessels in vitro differ with vessel segment. We performed this study to test the hypothesis that t hese vessel-specific cerebral artery norepinephrine (NE)-induced contr actility changes are mediated in part by differences in alpha(1)-adren ergic receptor (alpha(1)-R) density (B-max) or antagonist dissociation constant (K-D), and/or inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] s ynthesis. In common carotid (Com), circle of Willis (Will, and middle cerebral arteries (MCA) from adult sheep we measured NE-induced contra ctions. We also quantified alpha(1)-R in these, and in anterior, middl e, and posterior (AMP) cerebral arteries and cerebral microvessels (Mi cro). In addition, we quantified NE-induced Ins(1,4,5)P-3 synthesis. p D(2) values of Com and MCA were 5.2 +/- 0.1 and 6.3 +/- 0.1, respectiv ely. In contrast, the MCA maximum response to NE compared with K+ was much lower than that of the Com. In the Com, Wil, AMP, and Micro, alph a(1)-R B-max, was 54 +/- 3, <5 +/- 2, 23 +/- 3, and 35 +/- 3 fmol/mg p rotein, respectively. K-D averaged 0.20 +/- 0.05 nM in the several ves sel groups. In Com and in AMP cerebral arteries, NE produced a rapid i ncrease in Ins(1,4,5)P-3 with a peak at 45 s, and 50% effective concen tration of 5.5 +/- 0.2 mu M. NE stimulated a 240% increase of Ins(1,4, 5)P-3 in both Com and AMP, whereas Wil showed essentially no response. The ovine MCA was more sensitive to NE than was the Corn. In contrast , MCA showed a much lower maximum contractile response to NE compared with K+. Cerebral arteries (AMP) had only about half the alpha(1)-R de nsity of the Com. In AMP cerebral arteries, both the basal and NE-stim ulated Ins(1,4,5)P-3 values were much less than those of the Com. In M CA, the ratio of Ins(1,4,5)P-3 response to alpha(1)-R B-max was much g reater than in Com. These findings suggest important artery-to-artery differences in components of the cerebrovascular alpha(1)-R-mediated c ontractile pathway. They also suggest considerable potential for modul ation of pharmacomechanical coupling and homeostatic regulation of cer ebrovascular tone.