Alteration of Contractile Function and Calcium Ion Movements in Vascular Smooth Muscle by Gentamicin and Other Aminoglycoside Antibiotics

Abstract

Experiments were conducted to examine the effects of certain aminoglycoside antibiotics on contractile responses and related calcium ion (Ca 2+ ) movements in isolated vascular smooth muscle. Gentamicin, kanamycin, and streptomycin decreased contractile responses produced by norepinephrine, histamine, and high K + in rabbit aortic strips. The inhibitory action of these antibiotics on mechanical function was more pronounced when the Ca 2+ concentration of the bathing solution was decreased from 1.5 mM (normal Ca 2+ solution) to 0.05 mM (low Ca 2+ solution). The uptake of radiocalcium ( 45 Ca) into the isolated media-intimal layer of rabbit aortae was decreased in a maintained manner by each antibiotic. With gentamicin, the inhibitory effect on 45 Ca uptake was shown to be dependent upon the concentration of gentamicin employed and to be more evident in a 0.1 mM Ca 2+ solution than in a normal Ca 2+ solution. In addition, the rate of 45 Ca efflux from the rabbit aortic media-intimal layer was increased in a sustained manner by gentamicin, streptomycin, and kanamycin. Furthermore, contractile responses induced by high K + and norepinephrine in canine carotid arterial strips were inhibited by gentamicin. Present findings indicate that aminoglycoside antibiotics interfere with Ca 2+ -linked events leading to activation of the contractile mechanism of vascular smooth muscle. These in vitro findings may partially explain the occurrence of in vivo cardiovascular depression that has occasionally been observed after the administration of chemically related antimicrobial agents.