AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 283: H1673-H1680, 2002. First published May 30, 2002; doi:10.1152/ajpheart.01034.2001
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Vol. 283, Issue 4, H1673-H1680, October 2002

Tyrosine kinases regulate intracellular calcium during alpha 2-adrenergic contraction in rat aorta

Rebecca W. Carter and Nancy L. Kanagy

Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131-5218

We have demonstrated enhanced contractile sensitivity to the alpha 2-adrenoreceptor (alpha 2-AR) agonist UK-14304 in arteries from rats made hypertensive with chronic nitric oxide synthase (NOS) inhibition (LHR) compared with arteries from normotensive rats (NR); additionally, this contraction requires Ca2+ entry. We hypothesized that tyrosine kinases augment alpha 2-AR contraction in LHR arteries by increasing Ca2+. The tyrosine kinase inhibitor tyrphostin 23 significantly attenuated UK-14304 contraction of denuded thoracic aortic rings from NR and LHR. However, tyrphostin 23 did not alter UK-14304 contraction in ionomycin-permeabilized aorta, which indicates that tyrosine kinases regulate intracellular Ca2+ concentration. The Src family inhibitor PP1 and the epidermal growth factor receptor kinase inhibitor AG-1478 did not alter alpha 2-AR contraction, whereas the mitogen-activated protein kinase extracellular signal-regulated kinase kinase inhibitor PD-98059 attenuated the contraction. Contraction to CaCl2 in ionomycin-permeabilized LHR rings was greater than in NR rings. UK-14304 augmented CaCl2 contraction in ionomycin-permeabilized rings from both groups but to a greater extent in LHR aorta. Together, these data suggest that alpha 2-AR stimulates contraction via two pathways. One, which is enhanced with NOS inhibition hypertension, activates Ca2+ sensitivity and is independent of tyrosine kinases. The other is tyrosine kinase dependent and regulates intracellular Ca2+ concentration.

nitric oxide synthase inhibition; vascular smooth muscle; sensitivity


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