Vol. 276, Issue 2, H464-H471, February 1999
Influence of chronic ethanol consumption on arterial
tone in young and aged rats
Mika
Kähönen1,4,
Kirsi
Karjala3,
Nina
Hutri-Kähönen1,5,
Xiumin
Wu1,
Pia
Jaatinen2,6,
Päivi
Riihioja2,
Antti
Hervonen2, and
Ilkka
Pörsti1,6
1 Department of Pharmacological
Sciences and 2 School of Public
Health, University of Tampere Medical School, FIN-33101 Tampere;
3 Department of Pharmacology and
Toxicology, University of Helsinki, FIN-00014 Helsinki; Departments
of 4 Clinical Physiology,
5 Pediatrics, and
6 Internal Medicine, Tampere
University Hospital, FIN-33521 Tampere, Finland
The aim of this work was to evaluate the effects
of long-term ethanol consumption on arterial responses in vitro in
young and aged rats. Therefore, Wistar rats (ages 3 and 29 mo,
respectively) were allocated to six groups: control-young,
sucrose-young, ethanol-young, control-aged, sucrose-aged, and
ethanol-aged. The ethanol-fed groups were given 25% ethanol by
intragastric gavage three times a day 4 days a week. Responses of
mesenteric arterial rings were examined in standard organ chambers
after 5 treatment weeks. In norepinephrine-precontracted arterial
rings, endothelium-dependent relaxations to acetylcholine, as well as
endothelium-independent relaxations to isoproterenol, were attenuated
in aged rats when compared with young controls. Relaxation responses to
isoproterenol, but not to acetylcholine and nitroprusside, were clearly
improved by ethanol treatment in both young and aged rats. The
cyclooxygenase inhibitor diclofenac, which reduces the synthesis of
dilating and constricting prostanoids, enhanced the relaxation to
acetylcholine in all three aged rat groups but was without significant
effect in the young rats. In the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl
ester the relaxation to acetylcholine in control and sucrose-fed aged
rats was markedly reduced compared with control rats, whereas in the
young controls and in both young and aged ethanol-exposed groups,
distinct relaxations to higher concentrations of acetylcholine were
still present. The endothelium-independent relaxations to cromakalim, a
hyperpolarizing vasodilator acting via ATP-sensitive potassium
channels, were also markedly augmented by ethanol feeding in both young
and aged rats. In conclusion, ethanol consumption in both young and
aged rats was associated with markedly improved arterial relaxations to
isoproterenol and cromakalim, as well as clearly augmented relaxation
to acetylcholine during inhibition of cyclooxygenase and nitric oxide
synthase. These findings suggest that especially the potassium
channel-related component of arterial relaxation was augmented by
long-term ethanol exposure.
arterial smooth muscle; aging; endothelium; hyperpolarization; Wistar rat
