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PPARα ligand clofibrate ameliorates blood pressure and vascular reactivity in spontaneously hypertensive rats

  
@article{APS7740,
	author = {Zivar Yousefipour and Mohammad Newaz},
	title = {PPARα ligand clofibrate ameliorates blood pressure and vascular reactivity in spontaneously hypertensive rats},
	journal = {Acta Pharmacologica Sinica},
	volume = {35},
	number = {4},
	year = {2016},
	keywords = {},
	abstract = {Zivar YOUSEFIPOUR1, Mohammad NEWAZ2
1College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA; 2College of Pharmacy, Chicago State University, Chicago, IL, USA
 
Aim: Peroxisome proliferator activated receptors (PPARs) are nuclear transcription factors that regulate numerous genes influencing blood pressure.  The aim of this study was to examine the effects of clofibrate, a PPARα ligand, on blood pressure in spontaneously hypertensive rats (SHR). 
Methods: Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), 8–9 weeks old, were randomly allocated into groups treated with vehicle or clofibrate (250 mg·kg-1·d-1, ip for 21 d).  Systolic blood pressure (SBP) was measured before and after the study period using tail-cuff plethysmography.  Rats were sacrificed under anesthesia and blood, urine and tissue samples were processed for subsequent analysis. 

Results: SHR rats showed significantly higher SBP compared with WKY rats (198±6 mmHg vs 93±7 mmHg), and a 3-fold increase in urinary protein excretion.  Clofibrate treatment reduced SBP by 26%±2% and proteinuria by 43%±9% in SHR but not in WKY rats.  The urinary nitrite/nitrate excretion in SHR rats was nearly 2-fold greater than that in WKY, and was further increased by 30%±4% and 48%±3%, respectively, following clofibrate treatment.  In addition, PPARα protein expression and PPARα activity were significantly lower in SHR than that in WKY rats.  Clofibrate treatment significantly increased PPARα protein expression and PPARα activity in SHR rats, but not in WKY rats.  Moreover, the vasoconstrictor response of aortic ring was markedly increased in SHRs, which was blunted after clofibrate treatment. 

Conclusion: PPARα contributes to regulation of blood pressure and vascular reactivity in SHR, and clofibrate-mediated reduction in blood pressure and proteinuria is probably through increased NO production.

 
Keywords: PPARα; clofibrate; hypertension; proteinuria; vascular reactivity
 
This study was supported by American Heart Association, Texas Affiliate grant (0365001Y to Dr Mohammad NEWAZ. We acknowledge the use of Research Centers in Minority Institutions (RCMI) facilities of Texas Southern University for this study.
* To whom correspondence should be addressed. 
E-mail mnewaz@csu.edu
Received 2013-7-29    Accepted 2013-12-23},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/7740}
}