Endothelium-Dependent GenderDifferences inthe Response of the Rat Pulmonary Arteryto theThromboxane Mimic(U46619)1

ABSTRACT The pulmonaryarteriesof ratswere studiedinorderto determine the existence of sexual dimorphism. Gender differences, in the sensitivity (EC@)and maximum contractility (T,,,@) of ring prepa rations of the main pulmonary arteries of adult male and female rats, were evaluated with the syntheticendoperoxideanalog [(15S)-hydroxy-11a,9a-(epoxymethano)-prosta-5Z, I 3E-dienoic acid,] (U46619) and norepinephrine. There were no significant gender differences in the T@ values obtained with either U46619 or norepinephnne. However, when the intimal surface of vessel segments from female rats was rubbed, U46619 but not norep inephnne elicited a significantly lower T@. In contrast, no change inT@ was observedwithdenudedvesselsegmentsfrommales. Removal of the endothelium did not significantly affect the ECse of U46619 or norepinephnne in segmentsfrom either sex. The inhibitory effect of verapamil on the U46619-induced contractile responsewas studiedon both intactand denudedvesselsfrom rats of both gender. The T@ of intact vesselsfrom males but not femaleswas significantly attenuatedby verapamil(P < .05). The ECrevalues with verapamil were not significantly different in any of the vessel preparations. We suggest that the endothelium of the pulmonaryartery of female rats significantly potentiates the contractile response to U46619 and attenuates the inhibitory effectof verapamil. Sexual dimorphism in the vascular reactivity of isolated pulmonary blood vessels is of considerable interest owing to the reported gender differences in the incidence of primary pulmonary hypertension. After sexual maturation, women pres ent with this disease three times more frequently than men (Wagenvoort and Wagenvoort, 1970). Recent studies demonstrate that the endothelium mediates the response of the underlying smooth muscle to several ago nists (DeMey and Vanhoutte, 1982; Singer and Peach, 1983) and may be involved in the development of pulmonary hyper tension (Molteni et at., 1984). An EDRF was reported by Furchgott and Zawadski (1980) and has subsequently been verified in various vascular preparations including the human pulmonary artery In addition to EDRF, the pulmonary endothelium may also release a contractile substance. Exuded lung surface fluid and lymph fluid collected during vasoconstriction, caused by bilat eral and unilateral hypoxia, elicited contractile responses of isolated helical strip preparations of the canine pulmonary artery (Benumofet at., 1978). In addition, hypoxic vasoconstric tion of porcine pulmonary artery rings requires the presence of the endothelium and may involve the release of an endothe lium-dependent contractile factor The purpose of this study was to investigate in pulmonary this drug is currently used in the clinic for treating primary pulmonary hypertension Methods Animals. A total of 51 mature(12 weeksof age)Sprague-Dawley rats from the Charles River Breeding Laboratories (Wilmington, MA) were housed in a controlled environment with food and water ad libitum. The females and males weighed 234.2 ±6.42 and 260.83 Â