Ethanol consumption alters the expression and reactivity of adrenomedullin in the rat mesenteric arterial bed.
OBJECTIVE
Adrenomedullin (AM) is a peptide that displays cardiovascular protective activity. We investigated the effects of chronic ethanol consumption on arterial blood pressure, vascular reactivity to AM and the expression of AM system components in the rat mesenteric arterial bed (MAB).


METHODS
Male Wistar rats were treated with ethanol (20% vol/vol) for 6 weeks. Systolic, diastolic and mean arterial blood pressure were monitored in conscious rats. Vascular reactivity experiments were performed on isolated rat MAB. Matrix metalloproteinase-2 (MMP-2) levels were determined by gelatin zymography. Nitrite and nitrate generation were measured by chemiluminescence. Protein and mRNA levels of pre-pro-AM, CRLR (calcitonin receptor-like receptor) and RAMP1, 2 and 3 (receptor activity-modifying proteins) were assessed by western blot and quantitative real-time polymerase chain reaction, respectively.


RESULTS
Ethanol consumption induced hypertension and decreased the relaxation induced by AM and acetylcholine in endothelium-intact rat MAB. Phenylephrine-induced contraction was increased in endothelium-intact MAB from ethanol-treated rats. Ethanol consumption did not alter basal levels of nitrate and nitrite, nor did it affect the expression of MMP-2 or the net MMP activity in the rat MAB. Ethanol consumption increased mRNA levels of pre-pro-AM and protein levels of AM in the rat MAB. Finally, no differences in protein levels or mRNA of CRLR and RAMP1, 2 and 3 were observed after treatment with ethanol.


CONCLUSIONS
Our study demonstrates that ethanol consumption increases blood pressure and the expression of AM in the vasculature and reduces the relaxation induced by this peptide in the rat MAB.
College of Nursing of Ribeirão Preto, University of São Paulo, Brazil.
Juliana T
JT
Rocha
Ulisses V
UV
Hipólito
Alisson
A
Martins-Oliveira
Daniela P C
DP
Tirapelli
Marcelo E
ME
Batalhão
Evelin C
EC
Carnio
Regina H
RH
Queiroz
Eduardo B
EB
Coelho
Thiago M
TM
Cunha
José E
JE
Tanus-Santos
Carlos R
CR
Tirapelli
D053607:Adrenomedullin / Q000378:metabolism*; D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D058286:Calcitonin Receptor-Like Protein / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D005786:Gene Expression Regulation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D058261:Receptor Activity-Modifying Proteins / Q000378:metabolism
D058286:Calcitonin Receptor-Like Protein; D058261:Receptor Activity-Modifying Proteins; D053607:Adrenomedullin; D000431:Ethanol; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat