INCREASED CA-2+ SIGNALING AFTER ALPHA-ADRENOCEPTOR ACTIVATION IN VASCULAR HYPERTROPHY

In an effort to explain the increased sensitivity to agonists of hypertrophic vascular muscle, intracellular Ca2+ concentration ([Ca2+]i)-signaling mechanisms were studied in normal and hypertrophic rat aortas from normotensive and coarctation-hypertensive rats. Based on both fura 2 fluorescence and acquorin luminescence measurements, qualitatively different patterns of Ca2+ mobilization occur in normal and hypertrophic rat aortic muscle. Normal rat aortic muscle contracts to phenylephrine with little or no increase in [Ca2+]i, whereas the angiotensin II-induced contraction is accompanied by a marked [Ca2+]i transient. In contrast, hypertrophic rat aortic muscle shows a dramatic increase in Ca2+ signaling after phenylephrine stimulation. Moreover, both the amplitude of the angiotensin-induced [Ca2+]i transient and the contractile sensitivity to this agonist are decreased in the hypertrophic muscle. Our results strongly suggest that the amplitude of the [Ca2+]i transient after agonist stimulation determines the contractile sensitivity and that there is an altered coupling of the alpha-adrenoceptor in the hypertrophic vascular muscle.