Atorvastatin upregulates nitric oxide synthases with Rho-kinase inhibition and Akt activation in the kidney of spontaneously hypertensive rats

Abstract

ATV upregulates eNOS and nNOS expressions with Rho-kinase inhibition and Akt activation in the kidney of SHRs. The renal nitric oxide system, Rho-kinase and Akt may contribute to the antihypertensive and renoprotective effects of statins.

Simvastatin and GGTI-2133, a geranylgeranyl transferase inhibitor, increase erythrocyte deformability but reduce low O2tension-induced ATP release

“…Statin drugs increase the expression of endothelial nitric oxide synthase (eNOS) by inhibiting Rho activity as a result of decreased Rho geranylgeranylation (15,44). Therefore, a statin-induced increase in eNOS expression can be used to indicate inhibition of Rho activity in an animal by measuring eNOS expression in highly vascularized tissues, such as those of the kidney (19). Increased expression and activity of eNOS and improved endothelial function associated with HMG-CoA reductase inhibitors are mediated through inhibition of the Rho/Rho kinase signaling pathway (36) and occur before any significant changes in serum cholesterol levels (32).…”

Critical Promoter Region for Statin-Induced Human Endothelial Nitric Oxide Synthase (eNOS) Transcription in EA.hy926 Cells

“…For instance, anti-inflammatory and anticoagulant activities of statins have been demonstrated 6) . Statins may also directly improve endothelial function and increase the expression and activity of eNOS [7][8][9] . Statins induce eNOS expression at least partly by stabilizing eNOS mRNA 10) , and these drugs may upregulate eNOS transcription.…”

Serum Lipids and Statin Treatment During Acute Stroke

“…The effect of statins on the cerebrovascular system and the brain tissue is based on their pleiotrophic effect beyond the direct lipid effect. The vasoeffective action is based on a direct upregulation of the endothelial nitric oxide synthase (eNOS), increase of the bioavialability of NO 20-22 [Ito et al, 2010;Laufs et al, 2000;Nakata et al, 2007;Yagi et al, 2010;Ye et al, 2008;] and inhibition of NADPH oxidase [Antoniades et al, 2010;Rueckschloss et al, 2001]. This vascular effect precedes the lipid one.…”

“…The multiple mechanisms of statins on ischemic brains are based on the different targets of action. Statins increase eNOS [Ito et al, 2010;Ye et al, 2008] and reduce activity of nicotinamide adenine dinucleotide phosphate oxidase and decrease endothelin 1 and 2 and the expression of AT 1 receptor [Yagi et al, 2010]. It also acts on the inflammatory system by decreasing the nkFB [Nakata et al, 2007;Ye et al, 2008] and the expression of interleukin (IL) 1p, IL6 and MCP.…”