Role of magnesium ions in the excitation of vascular smooth muscle : effects of hypermagnesaemia and hypomagnesaemia on drug-induced contractions of mammalian arteries with special reference to the involvement of changed tissue calcium ion concentration or distribution in the observed responses
Studies on the perfused rabbit ear artery preparation showed that withdrawal of Mg 2+ from extracellular fluid potentiated the responses to histamine and ATP but not to catecholamines. Similar results were obtained in [2xCa2+] Krebs solution. Increases in [Mg 2+] decreased responses to the three agonists to a similar extent. In subsequent experiments attempts were made to alter the availability of calcium for contraction induced by these agonists either by changing the [Ca 2+] of the Krebs solution or by using Ca 2+ influx inhibitors, ouabain and ryanodine. The effects of these agonists were compared to those observed when Mg2+ was altered. In general, the results obtained in perfused rabbit ear artery supported the hypothesis that changes in extracellular [Mg2+] affect the availability of calcium for contraction but were not consistent with the suggestion that Mg2+ alters Ca2+ influx. In a second type of preparation tension responses of superfused rings of ear artery were studied. Responses to changes in extracellular [Ca2+] and[ Mg2+] were found to differ slightly from those obtained in the perfused artery. A simultaneously perfused and superfused arterial preparation showed that responses to changes in [ Mg2+] and[Ca2+] were different if the agonist was administered to the adventitial surface of the vessel rather than via the intimal surface. The effects of alterations in extracellular [Mg 2+] were studied in mesenteric arteries from weight matched normotensive and spontaneously hypertensive rats (SHR). No differences in response to NA or ATP when extracellular [Mg 2+ ] was either increased or reduced were observed in the SHR compared to the normotensive animal. However, a difference in calcium dependence was demonstrated between the two types of vessels to NA. In contrast to mesenteric arteries, experiments on aortae from normotensive rats and SHR showed no differences in the calcium dependence of NA responses between normotensive and SHR vessels, whereas, [4xMg2+ ] Krebs solution reduced the responses of normotensive aorta to NA more than SHR. These results in the rat were not consistent with the hypothesis that alteration in [Mg 2+] can be explained in terms of altered calcium availability. Attempts to increase intracellular cyclic AMP with theophylline showed that the response to ED50 NA in both mesenteric arteries and aortae from normotensive were reduced more than SHR. It is concluded that the effect of changes in extracellular [Mg2+] on the reactivity of vascular muscle varies depending on the type of vessel and species of animal from which the vessel is taken. In addition when all the experimental results are considered, it is not possible to explain all the actions of altered [ Mg2+ ] simply in terms of changed calcium availability.