Vascular smooth muscle cell signaling mechanisms for contraction to angiotensin II and endothelin-1

Brandi M. Wynne, Chin Wei Chiao, R. Clinton Webb

Research output: Contribution to journalReview articlepeer-review

136 Scopus citations


Vasoactive peptides, such as endothelin-1 and angiotensin II, are recognized by specific receptor proteins located in the cell membrane of target cells. After receptor recognition, the specificity of the cellular response is achieved by G-protein coupling of ligand binding to the regulation of intracellular effectors. These intracellular effectors will be the subject of this brief review on contractile activity initiated by endothelin-1 and angiotensin II. Activation of receptors by endothelin-1 and angiotensin II in smooth muscle cells results in phospholipase C activation leading to the generation of the second messengers inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 stimulates intracellular Ca2+ release from the sarcoplasmic reticulum and DAG causes protein kinase C activation. Additionally, different Ca2+ entry channels, such as voltage-operated, receptor-operated, and store-operated Ca2+ channels, as well as Ca2+-permeable nonselective cation channels, are involved in the elevation of intracellular Ca2+ concentration. The elevation in intracellular Ca2+ is transient and initiates contractile activity by a Ca2+-calmodulin interaction, stimulating myosin light chain (MLC) phosphorylation. When the Ca2+ concentration begins to decline, Ca2+ sensitization of the contractile proteins is signaled by the RhoA/Rho-kinase pathway to inhibit the dephosphorylation of MLC phosphatase (MLCP), thereby maintaining force generation. Removal of Ca2+ from the cytosol and stimulation of MLCP initiates the process of smooth muscle relaxation. In pathologic conditions such as hypertension, alterations in these cellular signaling components can lead to an overstimulated state causing maintained vasoconstriction and blood pressure elevation.

Original languageEnglish (US)
Pages (from-to)84-95
Number of pages12
JournalJournal of the American Society of Hypertension
Issue number2
StatePublished - Mar 2009


  • Calcium channel
  • Rho-kinase
  • phosphoinositides
  • vasoactive peptides

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine


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