Gender Difference in the Contribution of an Indomethacin-Sensitive Constrictor Factor to Phenylephrine Responsiveness in Rat Mesenteric Arteries
The mechanism for gender differences in cardiovascular disease may be due, in part, to differences in vascular function. Based on previous studies from our laboratory, we hypothesized that there is enhanced production of a vasoconstrictor cyclooxygenase product in arteries from males when compared to those from females. We studied three month-old male and female Sprague-Dawley rats (n=6 in each group). Small mesenteric arteries (∼400 μm) were isolated, pressurized, and the outer diameter was measured. Arteries from each rat were paired: one had intact endothelium (ENDO +) and the other was mechanically denuded (ENDO -). Dose-response curves to the α1-adrenergic agonist, phenylephrine (PE), were performed in the absence and presence of the cyclooxygenase inhibitor, indomethacin (INDO; 10 μM). Negative log EC50 values were calculated as an index of PE sensitivity and compared between groups using ANOVA and lsd. There were no differences in the sensitivity to PE in ENDO + arteries from males (6.07±0.07) and females (6.12±0.10, p=0.93). In ENDO + arteries from females, the PE sensitivity was unchanged in the presence of INDO (6.11±0.13, p=0.94 when compared to control). However, INDO significantly decreased PE sensitivity in ENDO + arteries from males (5.70±0.08, p=0.01 when compared to control). Endothelium denudation had no significant effect on PE sensitivity in males or females. In denuded arteries from females, INDO produced no change in PE sensitivity (denuded female: 6.08±0.09, denuded + INDO: 5.88±0.13, p=0.23). In contrast, INDO produced a significant decrease in sensitivity in denuded arteries from males (denuded male: 6.33±0.14, denuded + INDO (5.94±0.09, p=0.03). The magnitude of the shift in PE sensitivity produced by INDO (Δ EC50)in males was equivalent in ENDO + (0.37±0.07) and ENDO - (0.39±0.09, p=0.9, Student’s t-test) arteries. In conclusion, arteries from male rats produce more of an indomethacin-sensitive vasoconstrictor factor than arteries from female rats. The site of enhanced production of this cyclooxygenase product in males is not the endothelium, but may be vascular smooth muscle.