Anti-platelet therapy with clopidogrel prevents endothelial dysfunction and vascular remodeling in aortas from hypertensive rats

Fernanda R. Giachini, Romulo Leite, David A. Osmond, Victor V. Lima, Edward W. Inscho, R Clinton Webb, Rita C. Tostes

Research output: Contribution to journalArticle

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Abstract

The aim was to investigate the beneficial effects of clopidogrel in thoracic aorta function and structure and to characterize if P2Y12 receptors contribute to these effects. Male Sprague Dawley rats were infused with angiotensin II [(Ang II) 60 ng.min-1, 14 days] or saline (control rats) and were simultaneously treated with clopidogrel (10 mg.kg -1.day-1) or vehicle. After 14 days, systolic blood pressure (mmHg) was similar in Ang II-hypertensive rats treated with clopidogrel or vehicle (199±9 vs. 190±11, respectively). Systolic blood pressure in control rats was not altered by clopidogrel treatment (128±1 vs. vehicle, 134±2). Endothelium-dependent relaxation induced by 2-MeS-ADP was decreased in aortas from vehicle-treated Ang II-hypertensive rats, compared to vehicle-treated control rats. This response was elicited via activation of P2Y1 and P2Y12 receptors. In the presence of L-NAME and indomethacin, 2-MeS-ADP induced contraction and this response was augmented in vehicle-treated Ang II-hypertensive rats, compared to vehicle-treated control rats. The contraction to 2-MeS-ADP was evoked by P2Y13 and P2Y12 receptor activation. Clopidogrel-treatment did not normalize relaxation or contractile responses induced by 2-MeS-ADP in aortas from Ang II-hypertensive rats. P2Y1 and P2Y12 protein expression was increased, whereas P2Y13 receptor expression was reduced in aorta from vehicle-treated Ang II-hypertensive rats. Endothelium-dependent relaxation upon acetylcholine-stimulation was reduced in vehicle-treated Ang II-hypertensive rats, and clopidogrel treatment was effective in improving endothelial function. Clopidogrel also prevented vascular remodeling, evidenced by augmented media thickness in aortas from Ang II-hypertensive rats. Clopidogrel has beneficial effects on the aortic endothelium of Ang II-hypertensive rats, but its effects do not seem to be directly related to the presence of P2Y12 receptors in this vessel. Copyright:

Original languageEnglish (US)
Article numbere91890
JournalPloS one
Volume9
Issue number3
DOIs
StatePublished - Mar 17 2014

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clopidogrel
Platelets
aorta
blood vessels
Angiotensin II
Aorta
Rats
angiotensin II
Blood Platelets
Rat control
therapeutics
rats
Therapeutics
Blood pressure
receptors
endothelium
Blood Pressure
Endothelium
Chemical activation
systolic blood pressure

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Anti-platelet therapy with clopidogrel prevents endothelial dysfunction and vascular remodeling in aortas from hypertensive rats. / Giachini, Fernanda R.; Leite, Romulo; Osmond, David A.; Lima, Victor V.; Inscho, Edward W.; Webb, R Clinton; Tostes, Rita C.

In: PloS one, Vol. 9, No. 3, e91890, 17.03.2014.

Research output: Contribution to journalArticle

Giachini, Fernanda R. ; Leite, Romulo ; Osmond, David A. ; Lima, Victor V. ; Inscho, Edward W. ; Webb, R Clinton ; Tostes, Rita C. / Anti-platelet therapy with clopidogrel prevents endothelial dysfunction and vascular remodeling in aortas from hypertensive rats. In: PloS one. 2014 ; Vol. 9, No. 3.
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AU - Lima, Victor V.

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AU - Webb, R Clinton

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