Experiments were conducted to examine the effects of certain aminoglycoside antibiotics on contractile responses.and related calcium ion (Ca2+) 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 Ca2+ concentration of the bathing solution was decreased from 1.5 mM (normal Ca2+ solution) to 0.05 mM (low Ca2+ solution). The uptake of radiocalcium ("'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 4"Ca uptake was shown to be dependent upon the concentration of gentamicin employed and to be more evident in a 0.1 mM Ca2+ solution than in a normal Ca2+ solution. In addition, the rate of 4"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 Ca2+-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.Severe hypotensive episodes have been observed occasionally in man (3,9,24,25) and repeatedly in experimental animals (3,4,18,20,21) after the administration of aminoglycoside antibiotics (neomycin-streptomycin group). Although the mechanism(s) involved in this adverse side effect has not been completely resolved, recent studies suggest that these agents may alter peripheral vascular smooth muscle contractility. In the constant flow-rate perfused hind-limb preparation of thf dog, Cohen et al.(3) observed that the intraarterial administration of streptomycin and kanamycin decreased hind-limb vascular resistance. Evidence of streptomycin-induced dilatation of the renal vasculature was obtained in the in situ perfused canine kidney by Wolf and Wigton (30). The pharmacologic action involved in this peripheral vasomotor effect has not been determined, but several reports have associated this group of antibiotics with alteration of calcium ion (Ca2+) function in certain mammalian organ systems.

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A series of five structurally distinct ACE inhibitors were evaluated for their ability to inhibit tissue ACE activity in the SHR after oral administration. In the first series of experiments, the ACE inhibitors captopril, enalapril, pentopril, CGS 14824A and CGS 16617 were given to groups of SHR at doses that produced a 15 to 20 mm Hg reduction in blood pressure within 1 hour. Under these conditions of dose and time, only captopril significantly inhibited brain ACE activity (43%), whereas inhibition of serum ACE activity ranged from 72% to 99% with these agents. Inhibition of aortic ACE activity ranged from 54% to 87%, and lung ACE inhibition varied from 50% to 83%. In the second series of experiments, SHR were administered higher doses of each ACE inhibitor such that these compounds produced peak reductions in blood pressure (-25 mm Hg to -33 mm Hg) within a range of 2 to 6 hours. When tissue ACE activity was measured at the time corresponding to peak reduction in blood pressure, all five ACE inhibitors produced a significant inhibition of brain ACE activity ranging from 21% to 76%. Serum ACE activity was almost completely inhibited by these agents, with the exception of captopril (62% inhibition). The inhibition of aortic ACE activity ranged from 79% to 99%, while the inhibition of lung ACE activity did not increase under these conditions. These data suggest that ACE inhibitors may exert their maximal antihypertensive effects by inhibiting ACE in vascular tissues and brain.

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