Altered agonist-induced Ca2+ mobilization in aortic smooth muscle cells from cardiomyopathic hamsters

We compared the responses to the Ca(2+)-mobilizing effects of norepinephrine (NE), endothelin-1 (ET), and arginine vasopressin (AVP) of primary cultures of vascular smooth muscle cells (VSMCs) from aortas of young (30-40 days old) cardiomyopathic (Bio 14.6 strain) and age-matched control hamsters. In Bio 14.6 VSMCs, saturating concentrations of NE and ET elicited increases in the intracellular Ca2+ concentration ([Ca2+]i), which reached approximately 50 and 62% of those in control VSMCs. AVP elicited a significant increase in [Ca2+]i only in Bio 14.6 VSMCs. In contrast, 10 microM ionomycin induced similar Ca2+ responses in both types of cells in the absence of extracellular Ca2+. Ligand binding assay revealed that maximal binding values for alpha 1-adrenergic antagonists and ET in Bio 14.6 VSMCs were 59-64 and 85% of those in control VSMCs. Thus VSMCs from aortas of Bio 14.6 hamsters had reduced reactivity to NE and ET but increased response to AVP. The reduced Ca2+ response of Bio 14.6 VSMCs to NE appeared to be due mainly to a decrease in the receptor number.