Altered expression of Gi-protein and adenylyl cyclase activity in hearts from one kidney one clip hypertensive rats

Abstract

These data suggest that 1K-1C hypertensive rats exhibit enhanced expression of Gialpha proteins and associated functions that may be attributable to the enhanced levels of Ang II in this model of hypertension.

Natriuretic Peptide Receptor-C Attenuates Hypertension in Spontaneously Hypertensive Rats

“…NPR-A and NPR-B are membrane guanylyl cyclase receptors, whereas NPR-C does not possess guanylyl cyclase activity. Two different subtypes of NPR-C with molecular mass of 67 and 77 kDa have been identified with a broad range of ligands, including ANP, brain natriuretic peptide, C-type natriuretic peptide, and C-ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] [des(Gln, 18 Ser, 19 Gly, 20 Leu, 21 ; however, C-ANP 4-23 is specific for NPR-C and has no affinity for NPR-A or NPR-B. 8,9 The 77-kDa protein is implicated in ligand internalization as a clearance receptor, 10 whereas 67-kDa protein is coupled to adenylyl cyclase inhibition through inhibitory guanine nucleotide regulatory protein Gi 7,11 or to activation of phospholipase C (PLC).…”

“…8,9 The 77-kDa protein is implicated in ligand internalization as a clearance receptor, 10 whereas 67-kDa protein is coupled to adenylyl cyclase inhibition through inhibitory guanine nucleotide regulatory protein Gi 7,11 or to activation of phospholipase C (PLC). 12 However, we showed that NPR-C activation by C-ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] and resultant decrease in cAMP levels contribute to the activation of phosphatidyl inositol turnover signaling and suggested a cross-talk between NPR-C-mediated adenylyl cyclase inhibition and PLC signaling pathways. 13 The activity of adenylyl cyclase is regulated by 2 guanine nucleotide regulatory proteins (G proteins): Gs (stimulatory) and Gi (inhibitory).…”

“…An increased expression of Gi proteins and their mRNA in hearts and aortae has been shown in several models of hypertensive rats including spontaneously hypertensive rats (SHRs). 3,[19][20][21] Furthermore, the inactivation of Giα proteins by a single injection of pertussis toxin in prehypertensive rats (2-week-old SHRs) has been reported to prevent the development of BP, 22 suggesting the implication of enhanced expression of Gi proteins in the pathogenesis of hypertension.…”

“…C-ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] that specifically interacts with NPR-C has been reported to decrease the levels of Giα proteins in A10 vascular smooth muscle cell (VSMC) 23 and in VSMC from SHRs. 24 In addition, C-ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] was also shown to attenuate the enhanced oxidative stress in VSMC from SHRs 24 that contributes to the enhanced expression of Giα proteins in SHRs.…”

“…24 In addition, C-ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] was also shown to attenuate the enhanced oxidative stress in VSMC from SHRs 24 that contributes to the enhanced expression of Giα proteins in SHRs. 25 Taken together, it may be possible that C-ANP 4-23 treatment of SHRs could also attenuate the high BP in SHRs.…”