Gender differences in the effect of age on electrical field stimulation (EFS)-Induced adrenergic vasoconstriction in rat mesenteric resistance arteries

Citation
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
ISSN journal
00223565 → ACNP
Volume
296
Issue
3
Year of publication
2001
Pages
782 - 788
Database
ISI
SICI code
0022-3565(200103)296:3<782:GDITEO>2.0.ZU;2-Q
Abstract
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.