Enhanced Expression of Gi-Protein Precedes the Development of Blood Pressure in Spontaneously Hypertensive Rats

Marcil, Josée; Thibault, Christelle; Anand‐Srivastava, Madhu B.

doi:10.1006/jmcc.1996.0343

Cited by 71 publications

(60 citation statements)

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“…PT (1.5 g/100 g body wt) did not appear to have adverse effects on the health of animals in the study, because all rats treated with PT maintained or gained weight during the period of the studies (body weights were as follows: for WKY rats, 160Ϯ7.8 g; for PT-treated WKY rats, 154Ϯ7.4 g; for SHR, 150Ϯ7.0 g; and for PT-treated SHR, 149Ϯ3.9 g). In addition, as reported earlier, 23 the ratio of heart weight to body weight was not different in 6-and 8-week-old SHR Figure 1. Effect of in vivo PT treatment on development of high BP.…”

Section: Effect Of In Vivo Pt Treatment On Development Of High Bpsupporting

confidence: 84%

“…21,23 PT-Catalyzed ADP Ribosylation ADP ribosylation of heart membranes by PT was performed as described previously. 15 The heart membranes were solubilized with Lubrol PX (0.3%; Sigma) at 25°C for 10 minutes and were centrifuged at 10 000g for 1 hour.…”

Section: Preparation Of Heart and Mesenteric Artery Particulate Fractionmentioning

confidence: 99%

“…Figure 5A shows the relationship between PT-induced inactivation of G i proteins with receptor-dependent functions. Angiotensin II (Ang II), C-ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] , and oxotremorine, which interact with Ang II type 1, ANP-C, and muscarinic receptor, respectively, and inhibit adenylyl cyclase activity through G i proteins, 27,28 inhibited adenylyl cyclase activity in hearts from 6-week-old SHR and WKY rats; however, as reported earlier, 15,23 the extent of inhibition was significantly greater in SHR. For example, Ang II, C-ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] , and oxotremorine inhibited adenylyl cyclase activity by Ϸ15%, 20%, and 30%, respectively, in WKY rats and Ϸ25%, 30%, and 45%, respectively, in SHR.…”

Section: Effect Of Pt Treatment On G I Functionsmentioning

confidence: 99%

“…[15][16][17] The increased levels of G i␣ were shown to be associated with hypertension and not with hypertrophy, 21 whereas the decreased levels of G s␣ were associated with hypertrophy and not with hypertension. 22 We have recently shown that the increased expression of G i␣ proteins occurs before the onset of hypertension in SHR 23 and in DOCA-salt hypertensive rats, 24 suggesting that the enhanced levels of G i␣ proteins may be one of the contributing factors in the pathogenesis of hypertension. The present studies were undertaken to investigate the effect of inactivation of G i␣ protein by pertussis toxin (PT) treatment on the development of high BP in SHR.…”

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Inactivation of Enhanced Expression of G _i Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats

Anand‐Srivastava

2002

Circulation Research

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Abstract-We have previously shown that the enhanced expression of G i proteins in spontaneously hypertensive rats (SHR) that precedes the development of high blood pressure may be one of the contributing factors in the pathogenesis of hypertension. In the present study, we demonstrate that the inactivation of G i proteins by intraperitoneal injection of pertussis toxin (PT, 1.5 g/100 g body wt) into 2-week-old prehypertensive SHR prevented the development of hypertension up to 4 weeks and that, thereafter, it started to increase and reached the same level found in untreated SHR after 6 weeks. A second injection of PT after 4 weeks delayed the increase in blood pressure for another week. The PT-induced decrease in blood pressure in 6-week-old SHR was associated with a decreased level of G i␣ -2 and G i␣ -3 proteins in the heart, as determined by in vitro ADP ribosylation and immunoblotting. The decreased level of G i proteins was reflected in decreased G i functions. Furthermore, an augmentation of blood pressure to the same level in PT-treated SHR as found in untreated SHR was associated with enhanced expression and function of G i . These results indicate that the inactivation of G i proteins by PT treatment in prehypertensive SHR attenuates the development of hypertension and suggest that the enhanced levels of G i proteins that result in the decreased levels of cAMP and associated impaired cellular functions may be contributing factors in the pathogenesis of hypertension in SHR. Key Words: pertussis toxin Ⅲ ADP ribosylation Ⅲ G proteins Ⅲ blood pressure Ⅲ spontaneously hypertensive rats G uanine nucleotide regulatory proteins (G proteins) are a family of GTP-binding proteins that play an important role in the regulation of a variety of signal transduction systems, including the adenylyl cyclase/cAMP system. The adenylyl cyclase system is composed of three components: receptor, catalytic subunit, and stimulatory (G s ) and inhibitory (G i ) guanine nucleotide regulatory proteins. 1,2 The stimulation and inhibition of adenylyl cyclase by hormones are mediated by these two distinct G proteins (G s and G i , respectively), which couple the receptor to the catalytic subunit. The G proteins are heterotrimeric and are composed of ␣, ␤, and ␥ subunits. The ␣ subunits bind and hydrolyze GTP and confer specificity in receptor and effector interactions. Molecular cloning has revealed four different forms of G s␣ resulting from the differential splicing of one gene 3-5 and three distinct forms of G i␣ (G i␣ -1, G i␣ -2, and G i␣ -3) encoded by three distinct genes. 6 All three forms of G i␣ (G i␣ 1 to G i␣ 3) are implicated in adenylyl cyclase inhibition 6 and in the activation of atrial K ϩ channels. 7 The adenylyl cyclase/cAMP system has been implicated in both the control of heart contractility and vascular smooth muscle tone. 8,9 The levels of cAMP are regulated by G s and G i proteins. G i protein and associated adenylyl cyclase signaling has been shown to be implicated in a variety of cellular functions, including ...

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Section: Effect Of In Vivo Pt Treatment On Development Of High Bpsupporting

confidence: 84%

Section: Preparation Of Heart and Mesenteric Artery Particulate Fractionmentioning

confidence: 99%

Section: Effect Of Pt Treatment On G I Functionsmentioning

confidence: 99%

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confidence: 99%

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Inactivation of Enhanced Expression of G _i Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats

Anand‐Srivastava

2002

Circulation Research

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“…Several studies implicate overexpression of G i proteins in some tissues in SHRs. [23][24][25][26][27] However, our studies suggest normal levels of G i proteins in SHR preglomerular microvessels 28 and indicate a role for the G i protein/phospholipase C/protein kinase C/c-src/phosphatidylinositol 3-kinase pathway in the interaction between Ang II and the G i signal transduction pathway in SHRs. 29 Although we do not know why coincidence signaling between the Ang II signal transduction pathway and the G i signal transduction pathway is enhanced in SHR kidneys, it appears to be because of a downstream event in the aforementioned signal transduction pathway.…”

Section: Discussionmentioning

confidence: 53%

Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II–Induced Renal Vasoconstriction

Dubinion

Zhu

et al. 2006

Hypertension

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Abstract-TheKey Words: receptors Ⅲ neuropeptides Ⅲ peptides Ⅲ hypertension T he renin-angiotensin system (RAS) is essential for the development and maintenance of genetic hypertension in spontaneously hypertensive rats (SHRs). 1,2 Moreover, transplantation studies reveal that, in addition to the RAS, the SHR kidney is pivotal to the pathophysiology of hypertension in the SHR. 3,4 Finally, the renal sympathetic nervous system also appears to importantly contribute to the pathophysiology of hypertension in SHRs. In support of this latter concept, chronic denervation of the SHR kidney both delays the development of hypertension and attenuates the maximum increase in blood pressure in SHR. [5][6][7][8] Thus, there appears to be a coinvolvement of the RAS, the sympathetic nervous system, and the kidney in SHR hypertension.Many studies have been performed in search of a possible explanation for the coinvolvement of the RAS and the kidney in SHR hypertension. In this regard, studies do not support an increased expression of renal angiotensin II (Ang II) receptors 9 or increased levels of circulating 10 or renal 11 Ang II; also, SHRs do not have altered renal Ang II degradation rates. 12 However, SHRs do exhibit increased renovascular responses to Ang II, 13,14 and this appears to be the explanation for the coinvolvement of the RAS and the kidney in SHR hypertension.Our previous research indicates that G i mediates, in part, the enhanced renovascular response to Ang II in SHR. For example, pertussis toxin, an inhibitor of G i , abolishes the increased renovascular response to Ang II in SHR. 15,16 Importantly, activation of renal sympathetic nerves leads to the release of neuropeptide Y (NPY). 17 NPY is an example of a pancreatic polypeptide (PP)-fold peptide, 18 and NPY binds with high affinity to Y 1 , Y 2 ,

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Angiotensin II Enhances the Expression of Giα in A10 Cells (Smooth Muscle): Relationship with Adenylyl Cyclase Activity

Palaparti

Anand‐Srivastava

1999

Archives of Biochemistry and Biophysics

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Enhanced Expression of Gi-Protein Precedes the Development of Blood Pressure in Spontaneously Hypertensive Rats

Cited by 71 publications

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Inactivation of Enhanced Expression of G _i Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats

Inactivation of Enhanced Expression of G _i Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats

Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II–Induced Renal Vasoconstriction

Angiotensin II Enhances the Expression of Giα in A10 Cells (Smooth Muscle): Relationship with Adenylyl Cyclase Activity

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Enhanced Expression of Gi-Protein Precedes the Development of Blood Pressure in Spontaneously Hypertensive Rats

Cited by 71 publications

References 0 publications

Inactivation of Enhanced Expression of G i Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats

Inactivation of Enhanced Expression of G i Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats

Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II–Induced Renal Vasoconstriction

Angiotensin II Enhances the Expression of Giα in A10 Cells (Smooth Muscle): Relationship with Adenylyl Cyclase Activity

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Inactivation of Enhanced Expression of G _i Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats

Inactivation of Enhanced Expression of G _i Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats