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(Hypertension. 1999;34:603-608.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Angiotensin II–Stimulated Induction of sis-Inducing Factor Is Mediated by Pertussis Toxin–Insensitive G_q Proteins in Cardiac Myocytes

Rachel A. Hunt; G. Jayarama Bhat; Kenneth M. Baker

From Pennsylvania State University College of Medicine, Henry Hood MD Research Program, Sigfried and Janet Weis Center for Research, 100 North Academy Ave, Danville, Pa.

Correspondence to Kenneth M. Baker, MD, Texas A&M University System Health Science Center, Building 162, 1901 South First St, Temple, TX 76504. E-mail kbaker{at}medicine.tamu.edu

Abstract—The Janus kinase–signal transducers and activators of transcription (JAK-STAT) pathway is stimulated by angiotensin II (Ang II) via the type 1 receptor after acute pressure overload in the heart. The purpose of this study was to determine whether activation of the JAK-STAT pathway by Ang II is dependent on G proteins. Ang II (100 nmol/L for 120 minutes) caused formation of sis-inducing factor (SIF) complexes and tyrosine phosphorylation of STAT proteins in neonatal rat ventricular myocytes. The percentage of change in Ang II–stimulated SIF induction was not affected by pertussis toxin (PTX) or GP antagonist-2A, compounds that inhibit activation of G_i and G_o proteins. In contrast, GP antagonist-2A, a peptide that selectively inhibits activation of G_q proteins, completely abolished Ang II–stimulated SIF induction and STAT3 tyrosine phosphorylation. Pretreatment of cardiac myocytes with U73122, an inhibitor of phosphatidylinositol-specific phospholipase C (PLC) activity, decreased Ang II–stimulated SIF induction and STAT3 tyrosine phosphorylation in a dose-dependent manner. Chelation of intracellular Ca²⁺ with BAPTA-AM did not alter Ang II–stimulated SIF induction. In contrast, pretreatment of cardiac myocytes with Ro-31-8220, a potent and specific inhibitor of protein kinase C (PKC), decreased Ang II–stimulated SIF induction in a dose-dependent manner. Ang II–stimulated SIF induction was abolished in cardiac myocytes after downregulation of PKC by treatment with PMA. From these data, we conclude that Ang II–stimulated SIF induction and STAT3 tyrosine phosphorylation is mediated by PTX-insensitive G proteins through a G_q-PLC-PKC–mediated pathway in neonatal rat ventricular myocytes.

Key Words: angiotensin II • pathway, JAK-STAT • G protein • myocytes, cardiac • phosphorylation

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