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1 The dose-response curves for angiotensin II and four analogues in rat colon and uterus, and in rabbit aorta, were obtained.2 The ED(50) values of angiotensin II as well as the ED(50)s and intrinsic activities of angiotensin analogues varied between the three organs.3 The interaction of two competitive antagonists with angiotensin II receptors was also examined. The K(I) values obtained with both antagonists on the uterus differed from the values on the other tissues.4 It is concluded that angiotensin II receptors may be different in the three organs examined.

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.

1 L-DOPA (1-2 mg i.v.) in the pithed rat reduced the arterial and increased the venous pressure responses to noradrenaline.2 Infusions of dopamine (4-8 mug kg(-1) min(-1)) and noradrenaline (500 ng kg(-1) min(-1)) also reduced the pressor responses to noradrenaline. The pressor response did not recover after stopping dopamine infusions, but it usually did so after stopping noradrenaline infusions.3 The effect of L-DOPA on the response to noradrenaline was prevented by the prior injection of the dopa decarboxylase inhibitor NSD 1024.4 The prior injection of the dopamine-beta-hydroxylase inhibitor diethyldithiocarbamate, only partially prevented the effect of L-DOPA on pressor responses to noradrenaline.5 The perfusion of noradrenaline (400 ng kg(-1) min(-1)) together with Krebs solution (10 ml/min) through an organ bath containing an isolated aortic strip, depressed the response of the strip to doses of noradrenaline after the infusion was stopped. Infusions of dopamine (0.5-8.0 mug kg(-1) min(-1)) had a similar effect. Fifteen minutes after adding L-DOPA (0.5 mg) to the bath and 10 min after washing it out, the response to noradrenaline was depressed in three out of four experiments.6 Infusions of noradrenaline (1 mug kg(-1) min(-1)) in an isolated heart perfused by Langendorf's method blocked the response to injected noradrenaline whilst perfusion was in progress. Infusions of dopamine (4-8 mug kg(-1) min(-1)) or of L-DOPA (200 mug kg(-1) min(-1)) did not have this effect.7 It is concluded that the effect of L-DOPA on pressor responses to noradrenaline in the pithed rat are mediated by its conversion to dopamine and noradrenaline.

1. The predominant effect of morphine, diamorphine, pethidine or nalorphine on the blood pressure of the anaesthetized cat or rabbit is hypotension although, occasionally, a pressor action may predominate or intervene.2. Possible mechanisms of the depressor phases of action have been studied on cardiac and vascular preparations both in situ and in vitro.3. While in the whole animal, catecholamine release from the adrenal medulla and histamine liberation may be implicated in the responses, the vasodilator and vascular relaxant actions of morphine and, probably, pethidine, nalorphine and diamorphine on the isolated preparations are not mediated by the liberation of known peripheral transmitters or autacoids or by interaction with their specific receptors.