Gender differences in the effect of age on electrical field stimulation (EFS)-Induced adrenergic vasoconstriction in rat mesenteric resistance arteries
Jc. Sullivan et Ca. Davison, Gender differences in the effect of age on electrical field stimulation (EFS)-Induced adrenergic vasoconstriction in rat mesenteric resistance arteries, J PHARM EXP, 296(3), 2001, pp. 782-788
Citations number
39
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
The objective of this study was to examine the effects of gender and age on
electrical field stimulation (EFS)-induced vasoconstriction. Fisher 344 ra
ts were studied: young females (YF, n = 38), young males (YM, n = 29), old
females (OF, n = 33), and old males (OM, n = 30). Isolated mesenteric resis
tance arteries (endothelium-intact or denuded) were pressurized, and outer
diameter was monitored. Dose-response curves were performed to KCl and phen
ylephrine (PE). EFS (0.1-16 Hz) responses were expressed as percentage of c
onstriction from baseline. Area under the curve (AUC) was calculated and co
mparisons were made using analysis of variance and t tests. Females became
less responsive to EFS-induced constriction with age, whereas constrictor r
esponses among males were unaffected (AUC: YF = 454 +/- 15, OF = 284 +/- 22
, p< 0.001; YM = 391 +/- 35, OM = 357 +/- 31, p = 0.22). Endothelial denuda
tion produced a significant increase in EFS-induced constriction in OF and
OM. Endothelium removal in OF increased the EFS constrictor response to the
level seen in arteries from YF. BQ 123 (ETA receptor antagonist) significa
ntly decreased EFS-induced constriction in YM and OM. In YM, SQ 29,548 [thr
omboxane A(2) (TXA(2))/PGH(2) receptor antagonist] and indomethacin depress
ed constrictor responses. There were no differences among groups in the sen
sitivity to KCl, but YF were the most sensitive to PE. In conclusion, EFS-i
nduced vasoconstriction declined with age among females but not males. The
decrease in EFS constrictor responses in OF may be due to a selective decre
ase in vascular smooth muscle sensitivity to adrenergic agonists and an inc
rease in the production of an endothelium-derived vasodilator. Among males
there is also an endothelin-1 and TXA(2)/PGH(2) component to EFS-induced co
nstriction that is absent among females.