Tyrosine kinase signaling pathways modulate angiotensin II induced calcium ([Ca2+]i) transients in vascular smooth muscle cells

Touyz, R.M. and Schiffrin, E.L. (1996) Tyrosine kinase signaling pathways modulate angiotensin II induced calcium ([Ca2+]i) transients in vascular smooth muscle cells. Hypertension, 27(5), pp. 1097-1103. (doi: 10.1161/01.HYP.27.5.1097)

Abstract

Tyrosine kinases have been implicated in vascular smooth muscle cell proliferation and contraction. Underlying mechanisms may involve Ca2+-dependent pathways. This study assesses relationships between angiotensin II (Ang II)–stimulated phospholipase C–mediated Ca2+ transients and tyrosine kinase–dependent pathways in vascular smooth muscle cells. Intracellular free Ca2+ concentration ([Ca2+]i) was measured in primary cultured unpassaged vascular smooth muscle cells derived from mesenteric resistance vessels of Wistar-Kyoto rats with the use of fura 2 methodology. [Ca2+]i effects of Ang II (1 nmol/L) were determined in vascular smooth muscle cells in which tyrosine kinase pathways were stimulated by insulin (70 μU/mL; 0.5 nmol/L), insulin-like growth factor-I (1 ng/mL; 0.13 nmol/L), or platelet-derived growth factor-BB (1 ng/mL; 0.04 nmol/L) and in cells in which tyrosine kinase was inhibited by specific inhibitors (1 μmol/L tyrphostin A-23 and genistein). Ang II elicited a rapid and transient [Ca2+]i response (from 94±8 to 239±5.8 nmol/L). Activation of the receptor tyrosine kinase by insulin, platelet-derived growth factor, and insulin-like growth factor-I significantly reduced (P<.01) Ang II–induced [Ca2+]i to 161±7, 189±3.7, and 183±5 nmol/L, respectively. In the presence of tyrphostin A-23 and genistein, Ang II–stimulated [Ca2+]i remained persistently elevated and failed to return to basal levels. Tyrphostin A-1, the inactive tyrphostin analogue, had no significant effect on Ang II–induced [Ca2+]i. This study demonstrates that activation of tyrosine kinase pathways reduces Ang II–elicited [Ca2+]i responses, whereas tyrosine kinase inhibition prevents [Ca2+]i recovery after agonist stimulation. Interaction between tyrosine kinase– and phospholipase C–dependent signaling pathways modulates vascular smooth muscle cell [Ca2+]i responses to Ang II.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Touyz, Professor Rhian
• Authors: Touyz, R.M., and Schiffrin, E.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• Publisher: American Heart Association
• ISSN: 0194-911X
• ISSN (Online): 1524-4563