TY - JOUR T1 - Gender Differences in the Effect of Age on Electrical Field Stimulation (EFS)-Induced Adrenergic Vasoconstriction in Rat Mesenteric Resistance Arteries JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 782 LP - 788 VL - 296 IS - 3 AU - Jennifer C. Sullivan AU - Cathy A. Davison Y1 - 2001/03/01 UR - http://jpet.aspetjournals.org/content/296/3/782.abstract N2 - The objective of this study was to examine the effects of gender and age on electrical field stimulation (EFS)-induced vasoconstriction. Fisher 344 rats 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 resistance arteries (endothelium-intact or denuded) were pressurized, and outer diameter was monitored. Dose-response curves were performed to KCl and phenylephrine (PE). EFS (0.1–16 Hz) responses were expressed as percentage of constriction from baseline. Area under the curve (AUC) was calculated and comparisons were made using analysis of variance and ttests. Females became less responsive to EFS-induced constriction with age, whereas constrictor responses among males were unaffected (AUC: YF = 454 ± 15, OF = 284 ± 22,p < 0.001; YM = 391 ± 35, OM = 357 ± 31, p = 0.22). Endothelial denudation 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) significantly decreased EFS-induced constriction in YM and OM. In YM, SQ 29,548 [thromboxane A2(TXA2)/PGH2 receptor antagonist] and indomethacin depressed constrictor responses. There were no differences among groups in the sensitivity to KCl, but YF were the most sensitive to PE. In conclusion, EFS-induced vasoconstriction declined with age among females but not males. The decrease in EFS constrictor responses in OF may be due to a selective decrease in vascular smooth muscle sensitivity to adrenergic agonists and an increase in the production of an endothelium-derived vasodilator. Among males there is also an endothelin-1 and TXA2/PGH2 component to EFS-induced constriction that is absent among females. The American Society for Pharmacology and Experimental Therapeutics ER -