Prostaglandin output from and the spontaneous inotropism of uterine horns isolated from underfed rats at different stages of the sex cycle. smooth muscle contractile influences of indomethacin and of methoxamine

Abstract

The influences of a period of 15 days of restricted diet (50% of the normal food intake) in rats sacrificed at different stages of the sex cycle (proestrus, estrus, metestrus and diestrus), were explored on: (1) the magnitude of uterine spontaneous phasic contractions (isometric developed tension= IDT); (2) the release of prostaglandins (PGs) F_2α and E₂; from the uterus and (3) the myometrial inotropic responses evoked by methoxamine and indomethacin. At estrus and at proestrus, preparations from restricted diet rats exhibited greater initial (postisolation) IDT and better contractile constancy during 60 min than did uteri from normal fed rats. This enhanced contractile constancy, but not that of preparations from control fed rats, was prevented by incubation “in vitro” with indomethacin (10⁻⁶M). At metestrus and at diestrus, uteri from normal fed rats presented higher initial levels of IDT and even more sustained contractile constancy than at estrus or at proestrus. Moreover, contractile profiles remained unaltered following the dietary restriction and the presence of indomethacin evoked similar negative inotropic actions in both experimental groups (fed and underfed). Dose-response curves for methoxamine documented its possitive, but different, inotropic actions in the two groups and at the four periods of the estrous cycle. Indeed, in the underfed group at estrus and at proestrous, dose-response curves for methoxamine were shifted to the left of those in fed controls,a situation prevented by indomethacin (10-6M); whereas at metestrus and at diestrus, no differences in the inotropic reactivity towards methoxamine between the two experimental groups, were detected. On the other hand, indomethacin shifted to the right dose-response curves for the agonist, both in preparations from normal fed and from restricted diet rats. The generation and release of PGF_2α and of PGE₂ were explored under normal and restricted diet conditions, both at estrus and at diestrus. Following the dietary restriction, the output of PGE₂ from estrous uteri was augmented in comparison to controls, whilst the release of PGF_2α was not affected. At diestrus, dietary restriction failed to alter the uterine output of either one of these PGs. Results suggest that a greater generation and release of PGE₂, following underfeeding, appears to subserve the increased spontaneous motility and the greater sensitivity of the rat uterus for — adrenoreceptor agonists.