Intracranial-Extracranial Differences in the Ca2+ Sensitivity of Rabbit Arteries

We have previously demonstrated that the ratio of calcium uptake to force production varies widely with age, artery size, and method of contraction in cerebral arteries. The present experiments were conducted to examine the possibility that these differences involve corresponding variations in contractile force-calcium rela- tions. Common carotid (COM), basilar (BAS), and middle cerebral (MCA) arteries from adult were denuded of endothelium and mounted in vitro for measurement of con- tractility. Following equilibration at optimum resting diameter, the arteries were per- meabilized (p-escin, 50 pg/ml) and depleted of intracellular Ca2+ by treatment with 1 pM A23187. Ca2+ depletion was verified by absence of any contracile response to either 25 mM caffeine or 1 pM inositol 1,4,5-trisphosphate. Then, in the continuous presence of 1 pM calmodulin, bath calcium concentration was raised from zero through 10 pM in half-log increments and the corresponding contractions were re- corded. For all permeabilized arteries, the maximum force produced by 10 pM Ca was greater than or equal to that produced by 120 mM potassium-Krebs in the same segment before skinning. The pD2 (-log ED,,) values for calcium averaged 6.39 i 0.03, 6.77 i 0.04, and 6.92 * 0.03 in COM, BA, and MCA segments, respectively. In arteries contracted by a constant submaximat concentration of calcium (0.1 pM for BAS and MCA, 0.3 pMfor COM), the addition of 5HT produced a dose-dependent and GDPpS-sensitive increase in tension of up to 44% maximum. GTPyS mimicked the effects of 5HT and prevented further increases in Ca force induced by 5HT. Together, these data demonstrate that cerebrovascular calcium sensitivity is an anatomically heterogenous, physiologically regulated parameter responsive to agonist-induced perturbations. (P.S.E.B.M. 1997, Vol 2141