Increased Ca2+ 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 aequorin 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.
Papageorgiou
P
P
Department of Cellular and Molecular Physiology, Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215.
Morgan
K G
KG
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D001017:Aortic Coarctation / Q000503:physiopathology; D002118:Calcium / Q000502:physiology*; D016257:Fura-2; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects*
D000804:Angiotensin II; D010656:Phenylephrine; D002118:Calcium; D016257:Fura-2