Abstract
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.
Footnotes
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Send reprint requests to: Dr. Jennifer C. Sullivan, Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Ave., Albany, NY 12208. E-mail: jsullivan{at}mcg.edu
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This work was supported by grants (to C.A.D.) from the National Institutes of Health (AG15658), the American Heart Association (9950341N), and (to J.C.S) Pharmaceutical Research and Manufacturers of America Foundation.
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This work is a part of the doctoral thesis of Jennifer C. Sullivan.
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A portion of this work was previously presented in abstract form at Experimental Biology 2000 [Sullivan JC and Davison CA (2000) Effect of age and gender on electrical field stimulation (EFS)-induced vasoconstriction. FASEB J14:A482.12].
- Abbreviations:
- EFS
- electrical field stimulation
- PE
- phenylephrine
- ET
- endothelin
- TXA2
- thromboxane A2
- PGH2
- prostaglandin endoperoxide 2
- LNA
- Nω-nitro-l-arginine
- AUC
- area under the curve
- ANOVA
- analysis of variance
- YF
- young female
- OF
- old female
- YM
- young male
- OM
- old male
- NO
- nitric oxide
- EDHF
- endothelium-derived hyperpolarizing factor
- Received July 28, 2000.
- Accepted November 3, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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