PMID- 37783376
OWN - NLM
STAT- MEDLINE
DCOM- 20231106
LR  - 20231106
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 217
DP  - 2023 Nov
TI  - AT(1) receptors modulate ethanol-induced loss of anticontractile effect of 
      perivascular adipose tissue.
PG  - 115840
LID - S0006-2952(23)00431-8 [pii]
LID - 10.1016/j.bcp.2023.115840 [doi]
AB  - Ethanol consumption activates renin-angiotensin-aldosterone system (RAAS), which 
      plays a major role in the pro-contractile and hypertensive effects linked to 
      ethanol. We hypothesized that ethanol consumption induces loss of the 
      anticontractile effect of perivascular adipose tissue (PVAT)through RAAS-mediated 
      mechanisms. We examined the contribution of angiotensin II type 1 receptors 
      (AT(1)R) to ethanol-induced PVAT dysfunction. With this purpose, male Wistar 
      Hannover rats were treated with ethanol 20 % (in volume ratio) and/or losartan 
      (antagonist of AT(1)R; 10 mg/kg/day, gavage) for 9 weeks. Losartan prevented the 
      increase in blood pressure and the loss of the anticontractile effect of PVAT 
      induced by ethanol consumption. PVAT dysfunction occurred after 3 and 9 weeks of 
      treatment with ethanol in an endothelium-dependent manner. Blockade of AT(1)R 
      prevented ethanol-induced reduction of adiponectin levels in PVAT from 
      ethanol-treated rats. Functional assays revealed that ethanol impaired the 
      anticontractile effect of PVAT-derived angiotensin (1-7) and endothelial nitric 
      oxide (NO). In conclusion, AT(1)R are implicated in ethanol-induced loss of the 
      anticontractile effect of PVAT. In PVAT, AT(1)R activation decreases the 
      production of adiponectin, a PVAT-derived factor that promotes vasorelaxation in 
      an endothelium-dependent manner. In the endothelium, AT(1)R favors the production 
      of superoxide (O(2)(*-)) leading to a reduction in NO bioavailability. These 
      responses impair the vasodilator action induced by PVAT-derived angiotensin 
      (1-7), which occurs via Mas receptors located in endothelial cells. 
      Ethanol-induced PVAT dysfunction favors vascular hypercontractility, a response 
      that could contribute to the hypertensive state associated with ethanol 
      consumption.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Awata, Wanessa M C
AU  - Awata WMC
AD  - Programa de Pos-Graduacao em Farmacologia, Faculdade de Medicina de Ribeirao 
      Preto, Universidade de Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil; 
      Laboratorio de Farmacologia, Escola de Enfermagem de Ribeirao Preto, USP, 
      Ribeirao Preto, Sao Paulo, Brazil.
FAU - Sousa, Arthur H
AU  - Sousa AH
AD  - Programa de Pos-Graduacao em Farmacologia, Faculdade de Medicina de Ribeirao 
      Preto, Universidade de Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil; 
      Laboratorio de Farmacologia, Escola de Enfermagem de Ribeirao Preto, USP, 
      Ribeirao Preto, Sao Paulo, Brazil.
FAU - de Mello, Marcela M B
AU  - de Mello MMB
AD  - Programa de Pos-Graduacao em Farmacologia, Faculdade de Medicina de Ribeirao 
      Preto, Universidade de Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil.
FAU - Dourado, Thales M H
AU  - Dourado TMH
AD  - Programa de Pos-Graduacao em Farmacologia, Faculdade de Medicina de Ribeirao 
      Preto, Universidade de Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil; 
      Laboratorio de Farmacologia, Escola de Enfermagem de Ribeirao Preto, USP, 
      Ribeirao Preto, Sao Paulo, Brazil.
FAU - Pinheiro, Lucas C
AU  - Pinheiro LC
AD  - Laboratorio de Farmacologia, Escola de Enfermagem de Ribeirao Preto, USP, 
      Ribeirao Preto, Sao Paulo, Brazil.
FAU - Elias-Oliveira, Jefferson
AU  - Elias-Oliveira J
AD  - Departamento de Bioquimica e Imunologia, Faculdade de Medicina de Ribeirao Preto, 
      USP, Ribeirao Preto, Sao Paulo, Brazil.
FAU - Rodrigues, Vanessa F
AU  - Rodrigues VF
AD  - Departamento de Bioquimica e Imunologia, Faculdade de Medicina de Ribeirao Preto, 
      USP, Ribeirao Preto, Sao Paulo, Brazil.
FAU - Carlos, Daniela
AU  - Carlos D
AD  - Departamento de Bioquimica e Imunologia, Faculdade de Medicina de Ribeirao Preto, 
      USP, Ribeirao Preto, Sao Paulo, Brazil.
FAU - Castro, Michele M
AU  - Castro MM
AD  - Programa de Pos-Graduacao em Farmacologia, Faculdade de Medicina de Ribeirao 
      Preto, Universidade de Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil.
FAU - Tirapelli, Carlos R
AU  - Tirapelli CR
AD  - Laboratorio de Farmacologia, Escola de Enfermagem de Ribeirao Preto, USP, 
      Ribeirao Preto, Sao Paulo, Brazil. Electronic address: crtirapelli@eerp.usp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231001
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Adiponectin)
RN  - JMS50MPO89 (Losartan)
RN  - 3K9958V90M (Ethanol)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Male
MH  - Rats
MH  - Animals
MH  - *Adiponectin/pharmacology
MH  - Losartan/pharmacology
MH  - Ethanol/toxicity
MH  - Endothelial Cells
MH  - Vasoconstriction
MH  - Rats, Wistar
MH  - Adipose Tissue
MH  - *Hypertension
MH  - Nitric Oxide/pharmacology
OTO - NOTNLM
OT  - Angiotensin II
OT  - Blood pressure
OT  - Ethanol
OT  - Perivascular adipose tissue
OT  - Renin-angiotensin-aldosterone system
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/03 00:41
MHDA- 2023/11/06 06:42
CRDT- 2023/10/02 19:24
PHST- 2023/08/25 00:00 [received]
PHST- 2023/09/28 00:00 [revised]
PHST- 2023/09/29 00:00 [accepted]
PHST- 2023/11/06 06:42 [medline]
PHST- 2023/10/03 00:41 [pubmed]
PHST- 2023/10/02 19:24 [entrez]
AID - S0006-2952(23)00431-8 [pii]
AID - 10.1016/j.bcp.2023.115840 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2023 Nov;217:115840. doi: 10.1016/j.bcp.2023.115840. Epub 2023 
      Oct 1.