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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Mechanisms underlying vascular hypocontractility induced by ethanol withdrawal: Role of cyclooxygenase 2-derived prostacyclin

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Gonzaga, Natalia A. [1, 2] ; Awata, Wanessa M. C. [1, 2] ; Tanus-Santos, Jose E. [1] ; Padovan, Julio C. [3] ; Tirapelli, Carlos R. [2]
Total Authors: 5
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Programa Posgrad Farmacol, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Escola Enfermagem Ribeirao Preto DEPCH, Fac Ciencias Farmaceut Ribeirao Preto DFQ, Ribeirao Preto, SP - Brazil
[3] Rockefeller Univ, Lab Blood & Vasc Biol, New York, NY 10065 - USA
Total Affiliations: 3
Document type: Journal article
Source: European Journal of Pharmacology; v. 847, p. 103-112, MAR 15 2019.
Web of Science Citations: 1

The effects on the vasculature produced by ethanol withdrawal include both vasodilatation and hypocontractility, although a detailed biochemical understanding of these processes is yet to be accomplished. Here, we sought to investigate some of the mechanisms underlying vascular hypocontractility induced by ethanol withdrawal. Male Wistar rats were treated with increasing doses of 3-9% ethanol (v/v) for 21 days and the impact of ethanol withdrawal on the vascular function was assessed 48 h after immediate ethanol suspension. Endothelium-denuded rat aortic rings showed a reduced contractile response to phenylephrine, angiotensin II, serotonin and KC1 after ethanol withdrawal, but the same phenomenon was not observed in endothelium-intact rings. Indomethacin, but not L-NAME, tiron, PEG-catalase and SC560, restored the contractile response to phenylephrine of endothelium-denuded aortas from abstinent rats. Hyporeactivity to phenylephrine induced by ethanol withdrawal was reversed by SC236, a selective cyclooxygenase (COX)-2 inhibitor. Similarly, Ro1138452, a selective prostacyclin IP receptor antagonist, reversed vascular hypocontractility induced by ethanol withdrawal. Increased concentrations of 6-keto-prostaglandin (PG)F-1(alpha), a stable product of PGI(2), was detected in endothelium-denuded aortas from abstinent rats, and this response was prevented by indomethacin. However, no changes in aortic PGE(2) levels were detected after ethanol withdrawal. In situ quantification of hydrogen peroxide (H2O2 ) and nitric oxide (NO) using fluorescent dyes revealed that ethanol withdrawal decreased the levels of these two compounds in the tunica media. Our studies show that the vascular hypocontractility induced by ethanol withdrawal is independent of the endothelium and it is mediated by PGI(2) derived from COX-2. (AU)

FAPESP's process: 15/22046-8 - Role of AT1 receptors on ethanol withdrawal-induced hypertension and vascular oxidative stress
Grantee:Carlos Renato Tirapelli
Support Opportunities: Regular Research Grants
FAPESP's process: 13/00808-8 - Consequences of ethanol withdrawal on the vasculature and the systemic and local renin-angiotensin system (ras)
Grantee:Carlos Renato Tirapelli
Support Opportunities: Regular Research Grants