alpha(1)-Adrenergic receptor subtype function in fetal and adult cerebral arteries

作者:Goyal Ravi; Mittal Ashwani; Chu Nina; Zhang Lubo; Longo Lawrence D*
来源:American Journal of Physiology - Heart and Circulatory Physiology, 2010, 298(6): H1797-H1806.
DOI:10.1152/ajpheart.00112.2010

摘要

Goyal R, Mittal A, Chu N, Zhang L, Longo LD. alpha(1)-Adrenergic receptor subtype function in fetal and adult cerebral arteries. Am J Physiol Heart Circ Physiol 298: H1797-H1806, 2010. First published March 26, 2010; doi:10.1152/ajpheart.00112.2010.-In the developing fetus, cerebral artery (CA) contractility demonstrates significant functional differences from that of the adult. This may be a consequence of differential activities of alpha(1)-adrenergic receptor (alpha(1)-AR) subtypes. Thus we tested the hypothesis that maturational differences in adrenergic-mediated CA contractility are, in part, a consequence of differential expression and/or activities of alpha(1)-AR subtypes. In CA from fetal (similar to 140 days) and nonpregnant adult sheep, we used wire myography and imaging, with simultaneous measurement of tension and intracellular Ca2+ concentration ([CaCa2+](i)), radioimmunoassay, and Western immunoblots to examine phenylephrine (Phe)-induced contractile responses. The alpha(1A)-AR antagonists (5-MU and WB-4101) completely inhibited Phe-induced contraction in adult but not fetal CA; however, [CaCa2+](i) increase was reduced significantly in both age groups. The alpha(1D)-AR antagonist (BMY-7378) blocked both Phe-induced contractions and CaCa2+ responses to a significantly greater extent in adult compared with fetal CA. In both age groups, inhibition of alpha(1A)-AR and alpha(1B)-AR, but not alpha(1D)-AR, significantly reduced inositol 1,4,5-trisphosphate responses to Phe. Western immunoblots demonstrated that the alpha(1)-AR subtype expression was only similar to 20% in fetal CA compared with the adult. Moreover, in fetal CA, the alpha(1D)-AR was expressed significantly greater than the other two subtypes. Also, in fetal but not adult CA, Phe induced a significant increase in activated ERK1/2; this increase in phosphorylated ERK was blocked by alpha(1B)-AR (CEC) and alpha(1D)-AR (BMY-7378) inhibitors, but not by alpha(1A)-AR inhibitors (5-MU or WB-4101). In conclusion, in the fetal CA, alpha(1B)-AR and alpha(1D)-AR subtypes play a key role in contractile response as well as in ERK activation. We speculate that in fetal CA alpha(1B)-AR and alpha(1D)-AR subtypes may be a critical factor associated with cerebrovascular growth and function.

  • 出版日期2010-6