Mineralocorticoid receptors contribute to ethanol-induced vascular hypercontractility through reactive oxygen species generation and up-regulation of cyclooxygenase 2

The effects on blood pressure produced byethanol consumption include both vasoconstriction and activation of the renin-angiotensin-aldosterone system (RAAS), although the detailed relationship between these processes is yet to be accomplished. Here, we sought to investigate the contribution of miner...

Full description

Saved in:
Bibliographic Details
Published in:European journal of pharmacology 2023-06, Vol.949, p.175723-175723, Article 175723
Main Authors: Dourado, Thales M.H., Assis, Victor O., Awata, Wanessa M.C., de Mello, Marcela M.B., Cárnio, Evelin C., Castro, Michele M., Tirapelli, Carlos R.
Format: Article
Language:English
Subjects:
Animals
Cyclooxygenase 2
Cyclooxygenase 2 - metabolism
Endothelium, Vascular
Ethanol
Ethanol - adverse effects
Hypertension - chemically induced
Hypertension - metabolism
Male
Mineralocorticoid receptors
Rats
Rats, Wistar
Reactive oxygen species
Reactive Oxygen Species - metabolism
Receptors, Mineralocorticoid - metabolism
Thromboxane A2
Up-Regulation
Vasoconstriction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The effects on blood pressure produced byethanol consumption include both vasoconstriction and activation of the renin-angiotensin-aldosterone system (RAAS), although the detailed relationship between these processes is yet to be accomplished. Here, we sought to investigate the contribution of mineralocorticoid receptors (MR) to ethanol-induced hypertension and vascular hypercontractility. We analyzed blood pressure and vascular function of male Wistar Hannover rats treated with ethanol for five weeks. The contribution of the MR pathway to the cardiovascular effects of ethanol was evaluated with potassium canrenoate, a MR antagonist (MRA). Blockade of MR prevented ethanol-induced hypertension and hypercontractility of endothelium-intact and -denuded aortic rings. Ethanol up-regulated cyclooxygenase (COX)2 and augmented vascular levels of both reactive oxygen species (ROS) and thromboxane (TX)B2, a stable metabolite of TXA2. These responses were abrogated by MR blockade. Hyperreactivity to phenylephrine induced by ethanol consumption was reversed by tiron [a scavenger of superoxide (O2∙–)], SC236 (a selective COX2 inhibitor) or SQ29548 (an antagonist of TP receptors). Treatment with the antioxidant apocynin prevented the vascular hypercontractility, as well as the increases in COX2 expression and TXA2 production induced by ethanol consumption. Our study has identified novel mechanisms through which ethanol consumption promotes its deleterious effects in the cardiovascular system. We provided evidence for a role of MR in the vascular hypercontractility and hypertension associated with ethanol consumption. The MR pathway triggers vascular hypercontractility through ROS generation, up-regulation of COX2 and overproduction of TXA2, which will ultimately induce vascular contraction. [Display omitted]
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2023.175723