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Modulation of Gi Protein Expression in Hypertension: Molecular Mechanisms

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Molecular Defects in Cardiovascular Disease

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Abstract

Guanine nucleotide regulatory proteins (G proteins) play a key role in the regulation of various signal transduction systems including adenylyl cyclase–cAMP and phospholipase C (PLC)–phosphatidylinositol turnover (PI). These proteins are implicated in the modulation of a variety of physiological functions such as platelet functions, including platelet aggregation, secretion, and clot formation, and cardiovascular functions, including arterial tone and reactivity. Several abnormalities in adenylyl cyclase activity, cAMP levels, G proteins, and PLC/PKC have shown to be responsible for the altered cardiac performance and vascular functions observed in cardiovascular disease states. The enhanced or unaltered levels of inhibitory G proteins (Giα-2 and Giα-3) and mRNA have been reported in different models of hypertension, whereas Gsα levels were shown to be unaltered. These changes in G protein were associated with functions. The enhanced levels of Giα proteins precede the development of blood pressure and suggest that overexpression of Gi proteins may be one of the contributing factors for the pathogenesis of hypertension. The augmented levels of Giα proteins and associated adenylyl cyclase signaling in hypertension were shown to be attributed to the enhanced levels of vasoactive peptides. In addition, enhanced oxidative stress in hypertension may also be responsible for the enhanced expression of Giα proteins observed in hypertension. The augmented levels of Giα(alpha) proteins and associated adenylyl cyclase signaling in hypertension appear to be attributed to the enhanced levels of vasoactive peptides, which by increasing oxidative stress and transactivating growth factor receptors enhance MAP kinase activity that contributes to the enhanced expression of Giα proteins observed in hypertension.

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  1. Department of Physiology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada

    Madhu B. Anand-Srivastava

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  1. Madhu B. Anand-Srivastava
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Correspondence to Madhu B. Anand-Srivastava .

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  1. St. Boniface General Hospital, Research Centre, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

  2. Jikei University School of Medicine, Shibuya-ku, Ebisu 3-31-6, Tokyo, 150-0013, Japan

    Makoto Nagano

  3. Czech Republic, Institute of Physiology, Academy of Sciences of the, Videnska 1083, Prague, 142 20, Czech Republic

    Bohuslav Ostadal

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Anand-Srivastava, M.B. (2011). Modulation of Gi Protein Expression in Hypertension: Molecular Mechanisms. In: Dhalla, N., Nagano, M., Ostadal, B. (eds) Molecular Defects in Cardiovascular Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7130-2_20

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