Mitogen-activated protein kinase activation: An alternate signaling pathway for sustained vascular smooth muscle contraction,☆☆,,★★

Presented in part at the Surgical Forum of the American College of Surgeons, San Francisco, Calif., Oct. 7, 1996.
https://doi.org/10.1016/S0741-5214(97)70196-4Get rights and content
Under an Elsevier user license
open archive

Abstract

Purpose: The vascular smooth muscle determines the dynamic caliber of the blood vessel and hence is the final effector cell in modulating vasomotor tone. Although considerable information is available regarding the physiologic agonists that induce contraction, less is known about the cellular signaling events that lead to long-lasting contractions or vasospasm. We examined the hypothesis that activation of mitogen-activated protein (MAP) kinase may be associated with sustained smooth muscle contractions.

Methods: Physiologic contractile responses were determined in intact bovine carotid artery smooth muscles in a muscle bath. Corresponding signaling events were determined with immunoblots using antiphosphotyrosine antibodies or immunoprecipitation of whole-cell phosphorylated strips of muscle.

Results: The tyrosine kinase inhibitor, genestein, significantly inhibited the magnitude of contractions induced by phorbol ester, endothelin, angiotensin, and serotonin. In addition, genestein inhibited the sustained phase of contractions induced by serotonin. Serotonin-induced vascular smooth muscle contractions were temporally associated with an increase in the phosphorylation of MAP kinase.

Conclusions: These data suggest that the activation of MAP kinase is associated with sustained vascular smooth muscle contractions. Pharmacologic manipulation of MAP kinase activation may lead to new approaches to treat pathologic circumstances of increased vasomotor tone such as vasospasm. (J Vasc Surg 1997 26:327-32.)

Cited by (0)

From the Department of Surgery (Drs. Epstein and Brophy), and the Institute of Molecular Medicine and Genetics (Drs. Throckmorton and Brophy), Medical College of Georgia; and the Augusta VA Medical Center (Dr. Brophy).

☆☆

Supported by a VA Merit Review and a Clinician Scientist Award from the American Heart Association.

Reprint requests: Colleen M. Brophy, MD, Department of Surgery, Medical College of Georgia, Augusta, GA 30912

★★

24/1/81291