Intracellular free Ca2+ is elevated in hypertrophic aortic muscle from hypertensive rats

Vessels from hypertensive animals have been shown to have increased medial thickness and also to exhibit increased sensitivity to agonists. We tested the hypothesis that changes in intracellular Ca2+ concentration [( Ca2+]i) may be associated with the growth response and the altered contractility of the aortic smooth muscle of modified coarctation-hypertensive rats. Freshly isolated single cells, loaded with fura-2, showed significantly higher [Ca2+]i both at rest and after depolarization compared with normal rat aortic cells. These cells also exhibited at rest a significant nuclear-cytoplasmic [Ca2+] gradient. Furthermore, the increased [Ca2+]i was associated with increased nuclear volumes, suggesting the presence of polyploid nuclei, as determined by ethidium dimer fluorescence imaging. Intact vascular rings from hypertrophic rat aortas, loaded with aequorin, also showed significantly higher [Ca2+]i at rest and after depolarization compared with normal rat aortas. In addition, the maximal force per cross-sectional area generated by the hypertrophic muscle was less than normal, consistent with a change in the contractile phenotype of the growing smooth muscle cells. This is the first report to directly indicate an increase in [Ca2+]i in hypertrophic vascular smooth muscle in hypertensive animals.