SCN − ions induce contraction of vascular muscle from male but not female rats

Abstract

It has been suggested that anions may play important roles in the regulation of membrane potentials, intracellular calcium and pH of vascular smooth muscle. It is, thus, possible that anions may be important in the sex-linked differences observed in contractile functions of vascular smooth muscle. With this in mind, we investigated the influence of alteration of the anionic environment, i.e., Cl − chloride ions, on the contractile activity of isolated aortic strips and rings from sexually mature male and female rats. After a few minutes of changing the incubation medium from normal chloride-containing Krebs-Ringer bicarbonate (NKRB) to a SCN − (thiocyanate) modified Krebs-Ringer bicarbonate solution (SCN-KRB; 118 mM SCN − substituted for 118 mM Cl −), resting tension increased dramatically, e.g., to about 85% of KCl maximum in males, but not in females. This increased resting tension could not be inhibited or attenuated by specific adrenergic, cholinergic, histaminergic, serotoninergic or cyclo-oxygenase inhibitors. Likewise use of a local anesthetic in high concentration (i.e., procaine HCl, 10 −3 M) also failed to inhibit or attenuate the SCN −-induced contractions. However, use of 5 mM EGTA, incubation in Ca 2+-free SCN-KRB media or addition of [Mg 2+] o (extracellular Mg 2+) (2.4–14.4 mM) all resulted in inhibition of the enhancement of vascular tone in aortas from male animals, whereas addition of 5 mM CaNa 2EDTA or removal of [Mg 2+] o from SCN −KRB potentiated it. Use of intact aortic rings or aortic strips produced identical results in response to SCN-KRB and the experimental maneuvers. Our results suggest that the gender differences in the contractile responsiveness of vascular smooth muscle are probably related to anionic metabolism and distribution of Cl − ions across the vascular smooth muscle cell membranes. Chloride and other anions may mediate the diverse effects and actions of sex hormones on vascular tone, reactivity and calcium movement in vascular smooth muscle.