Modulation of Gi Proteins in Hypertension: Role of Angiotensin II and Oxidative Stress

Author(s): Madhu B. Anand-Srivastava

Journal Name: Current Cardiology Reviews

Volume 6 , Issue 4 , 2010

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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)/phosphatidyl inositol turnover (PI). These are implicated in the modulation of a variety of physiological functions such as platelet functions, cardiovascular functions, including arterial tone and reactivity. Several abnormalities in adenylyl cyclase activity, cAMP levels and G proteins 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 expression were associated with Gi 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 vasoactive peptides, including angiotensin II (AngII), were shown to contribute to enhanced expression of Giα proteins and associated adenylyl cyclase signaling and thereby increased blood pressure. In addition, enhanced oxidative stress in hypertension due to Ang II may also be responsible for the enhanced expression of Giα proteins observed in hypertension. The mechanism by which oxidative stress enhances the expression of Gi proteins appears to be through the activation of mitogen activated protein (MAP) kinase activity.

Keywords: G-proteins, Angiotensin II, oxidative stress, MAPkinase, adenylyl cyclase, hypertension, neurotransmitter, inorganic phosphate, sarcoplasmic, deoxycorticosterone, antihypertensive, nitrendipin, losartan, cAMP, mRNA, volume-overload hypertro-phy

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Article Details

Year: 2010
Page: [298 - 308]
Pages: 11
DOI: 10.2174/157340310793566046
Price: $65

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