The effect of 17β‐oestradiol on regional blood flow in anaesthetized pigs

The present study was designed to investigate the effects of 17β-oestradiol on the mesenteric, renal, iliac and coronary circulations and to determine the mechanisms involved. In pigs anaesthetized with sodium pentobarbitone, changes in blood flow in the superior mesenteric, left renal, left external iliac and left circumflex coronary arteries caused by intravenous infusion of 17β-oestradiol at constant heart rate and arterial pressure were assessed using electromagnetic flowmeters. In eight pigs, infusion of 2 μg h−1 of the hormone caused an increase in renal, iliac and coronary blood flow without affecting mesenteric blood flow, left ventricular dP/dtmax (rate of change of left ventricular systolic pressure) and filling pressures of the heart. In four pigs, these vasodilator effects were enhanced by graded increases in the dose of the hormone between 1, 2 and 3 μg h−1; the highest dose also caused an increase in mesenteric blood flow. In five pigs, blockade of muscarinic cholinoceptors and adrenoceptors with the intravenous administration of atropine, propranolol and phentolamine did not affect the vasodilator responses caused by infusion of 2 μg h−1 of 17β-oestradiol. The increases in renal, iliac and coronary blood flow caused by infusion of 2 μg h−1 of 17β-oestradiol were prevented, respectively, by the injection of Nω-nitro-L-arginine methyl ester (L-NAME) into the renal artery (five pigs), the iliac artery (five pigs) or the coronary artery (five pigs). In five pigs, all responses were prevented by injection of L-NAME into all three arteries. In two pigs, injection of L-NAME into the mesenteric, renal, iliac and coronary arteries abolished the vasodilator responses to the infusion of 3 μg h−1 of 17β-oestradiol. The present study shows that intravenous infusion of 2 μg h−1 of 17β-oestradiol primarily dilated renal, iliac and coronary circulations and that a higher dose of the hormone also caused vasodilatation in the mesenteric vascular bed. The mechanism of these responses was shown to be nitric oxide dependent. It is widely accepted that oestrogens have a vasodilator effect on the coronary, genito-urinary and limb vasculature (Magness et al. 1993; Volterrani et al. 1995; Riedel et al. 1995; Rosenfeld et al. 1996) and are thought to play an important role in the lower incidence of cardiovascular disease in women (Samaan & Crawford, 1995). Controlled experiments in animals have shown that acute administration of 17β-oestradiol causes relaxation of coronary smooth muscle (Collins et al. 1994; Wellman et al. 1996; Lamping & Nuno, 1996; Thompson & Weiner, 1997) and vasodilatation (Eckstein et al. 1994; Gorodeski et al. 1995; Sudhir et al. 1995). However, little is known about the effect of this hormone on abdominal, renal and iliac vascular beds despite their known involvement in cardiovascular regulation. Indeed it has been reported in ewes that these vascular beds are not responsive to this hormone (Nuwayhid et al. 1975). Also, renal blood flow in the rat is suggested to increase following administration of 17β-oestradiol (Kapitola et al. 1994) and to decrease in women at high plasma levels of the hormone (Oelkers, 1996). The mechanisms of the known regional vasodilator effect of oestrogens have been controversial. In isolated vessels such as the aorta (Cheng et al. 1994; Paredes-Carbajal et al. 1995) and the coronary artery (Collins et al. 1994; Wellman et al. 1996; Thompson & Weiner, 1997) and in the isolated perfused heart (Gorodeski et al. 1995), the vasodilatation has been attributed mainly to nitric oxide. In anaesthetized dogs this mechanism was not confirmed as the cause of oestrogen-induced coronary vasodilatation (Sudhir et al. 1995). The present investigation was planned to find out the effect of acute administration of 17β-oestradiol on mesenteric, renal, iliac and coronary blood flow in anaesthetized female pigs and to determine whether the mechanism of this effect involved vascular muscarinic cholinoceptors and adrenoceptors and/or nitric oxide. For this purpose, experiments were performed under constant heart rate and arterial pressure to avoid interference from systemic reflex responses and local effects.