Anti-hypertensive effects of Rosuvastatin are associated with decreased inflammation and oxidative stress markers in hypertensive rats.
Among their pleiotropic effects, statins exert antioxidant and anti-inflammatory properties. The aim of this study was to evaluate in normotensive (WKY) and in spontaneously hypertensive rats (SHR) the effect of rosuvastatin (ROSU) treatment on (1) plasma inflammation markers and endogenous NO synthase inhibitor (ADMA) levels, (2) reactive oxygen species (ROS) generated by circulating leukocytes and (3) vascular oxidative stress and tissue inflammation markers. Plasma cytokines were higher in SHR than in WKY, except for IL-4, which was lower in SHR than in WKY. SHR monocytes exhibited higher production of ROS than did WKY monocytes. In the experimental conditions, ROSU did not modify plasma cholesterol levels in SHR but attenuated the increase in systolic blood pressure. In SHR only, ROSU lessened pro-inflammatory cytokines and ADMA levels, increased IL-4 and reduced ROS production in circulating monocytes. These results demonstrate the beneficial effects of ROSU in SHR, independently of any lowering of cholesterol levels.
Sicard
Pierre
P
Laboratory of Experimental Cardiovascular Pathophysiology and Pharmacology, Faculties of Medicine and Pharmacy, Dijon, France. sicard123@yahoo.fr
Delemasure
Stéphanie
S
Korandji
Claudia
C
Segueira-Le Grand
Anabelle
A
Lauzier
Benjamin
B
Guilland
Jean-Claude
JC
Duvillard
Laurence
L
Zeller
Marianne
M
Cottin
Yves
Y
Vergely
Catherine
C
Rochette
Luc
L
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001794:Blood Pressure; D005464:Fluorobenzenes / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*
D000959:Antihypertensive Agents; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D015847:Interleukin-4; C018524:N,N-dimethylarginine; D000068718:Rosuvastatin Calcium; D001120:Arginine; D019255:NADPH Oxidases