Hypocapnic constriction in rabbit basilar artery in vitro: triggering by serotonin and dependence on endothelin-1 and alkalosis

This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by serotonin, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic alkaline solution (25 mM NaHCO(3); pH 7.76; pCO(2) 14.2) or isocapnic alkaline solution (50 mM NaHCO(3); pH 7.73; pCO(2) 35.0) rarely altered basal tension. Serotonin (3 muM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension. Washout of the serotonin did not decrease tension in 54% of the tissues, as plateau tension was maintained for 2-2.5 h. The plateau tension of washed tissues was relaxed by 1-3 muM PD145065 (Ac-D-Bhg-L-Leu-Asp-L-Ile-L-Ile-L-Trp), BQ610 (homopiprridinyl-CO-Leu-D-Trp(CHO)-D-Trp), and BQ788 (N-cis-2,6-dimethyl-piperidinocarbonyl-L-gamma -MeLeu-D-Trp (COOCH(3))-Nle), endothelin ET(A)/ET(B), endothelin ET(A), and endothelin ET(B) receptor antagonists, respectively. In contrast, serotonin-induced tension in normal solution (25 mM NaHCO(3); pH 7.42; pCO(2) 36.9) was maintained for only 40 min (mean). These results demonstrate that (1) constriction due to hypocapnia in vitro can be triggered by serotonin and is endothelin-1 mediated and (3) alkaline pH in the absence of decreased pCO(2) is sufficient to elicit the constriction triggered by serotonin. (C) 2000 Elsevier Science B.V. All rights reserved.