APPS November 2002 Meeting Abstract 2425


Hala A. Raghib, Timothy V. Murphy, Harry Majewski, Division of Biosciences, School of Medical Sciences, RMIT University, Vic.

The incidence and severity of cardiovascular disease is lesser in pre-menopausal women than men of the same age. The beneficial effects of estrogen on the cardiovascular system may partly explain in this effect1. The current study attempted to examine the role of estrogen in altering the expression and activity of cyclo-oxygenase (COX), an enzyme involved in regulation of vascular tone through metabolism of arachidonic acid to produce the vasodilator prostacyclin and the vasoconstrictor thromboxane A2, amongst other prostanoids. The expression of the COX isoenzymes 1 and 2 in the aorta from age-matched male, female and ovariectomised female Sprague-Dawley rats was assessed by western blotting. COX enzyme activity was measured using rings of aorta isolated from the three models and mounted in an organ bath containing warmed (37C), oxygenated Kreb's solution. The α1-adrenoceptor agonist phenylephrine (10 M) was used to stimulate COX activity and samples of bathing fluid were collected and analysed for 6-keto PGF1α, a stable metabolite of prostacyclin, using EIA. Ovariectomy increased the expression of both COX-1 and 2 in the aorta of female rats, COX-1 (but not COX-2) expression was also higher in male rats compared to female rats. In studies measuring COX activity, basal 6-keto PGF1α production was higher in the aorta from female rats compared to ovariectomised or male rats. Both the COX-1 inhibitor piroxicam (100 M) and the COX-2 inhibitor NS-398 (10 M) reduced basal 6-keto PGF1α production in all three models, suggesting that both COX-1 and 2 contributed to prostacyclin production. Phenylephrine increased 6-keto PGF1α production significantly in female aortas only, an effect blocked by both piroxicam and NS-398. These observations suggest that estrogen may decrease COX expression in the aorta, however the relationship between estrogen and COX activity may be a complex one involving other enzymes and arachidonic acid levels.

(1) Geary G, Krause D, Duckles S. American Journal of Physiology. 2000;279:511-519.

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