Observations of idazoxan and xylazine on the myometrial response of the normal, cycling virgin rat in vitro

Abstract

The aim of this study was to determine the contractile responses of normal virgin rat uterine smooth muscle to the ⍺₂ adrenergic agonist, xylazine HCl, in the presence or absence of the selective ⍺₂ adrenoceptor blocker, idazoxan HCl. Sections of full thickness uterus measuring 5 x 1 x 1 mm taken from mature, virgin Sprague-Dawley rats were used in isolated tissue baths containing 37°C Krebs-bicarbonate solution, and continually aerated with 95% O₂ and 5% CO₂. Following stabilization of spontaneous contractions, the tissues were exposed to either no idazoxan (control), 10⁻⁵ M idazoxan (low), 10⁻⁴ M idazoxan (medium), or 10⁻³ M idazoxan (high). Five minutes later, xylazine was added to all baths in a cumulative manner at quarter log increments from 1 x 10⁻⁵ through 1 x 10⁻³ M. The % response in peak developed tension and effective concentration resulting in a 50% response (EC₅₀) for the four treatment groups were examined. Results indicated that xylazine alone, at a concentrations greater than 1 x 10⁻⁴ M, caused a significant negative inotropic response. Pre-treatment with idazoxan at a concentration greater than 10⁻⁴ M enhanced the negative inotropic effect of xylazine in a dose-dependent manner. The mechanism of this synergism is unknown but is proposed to be a local anesthetic action due to sodium channel blockade.