Differential regulation of circulating Mg2+ in the rat by beta 1- and beta 2-adrenergic receptor stimulation

Extracellular Mg2+ homeostasis was studied in vivo in the anesthetized rat. Animals were infused with isoproterenol (ISO) for 10 minutes, and serum Mg2+ was measured after the infusion and then 10 and 20 minutes later. A dose-dependent increase in circulating Mg2+ was observed in animals infused with ISO at a rate of 0.1 microgram.kg-1.min-1 or higher. The time course of the effect demonstrated that circulating Mg2+ continued to increase 20 minutes after the end of the ISO infusion. A predicted maximal increase in serum Mg2+ concentration of 19.3% was derived with a predicted EC50 of 0.08 microgram.kg-1.min-1. The maximal percent increase corresponded to a net increase of 6.7 mumol/300 g body wt. Because infusion of ISO resulted in changes in hemodynamic parameters, most notably a drop in blood pressure, a group of animals was infused with nitroprusside to mimic the hypotensive response via a nonadrenergic mechanism. Under these conditions, there was a transient increase in circulating Mg2+ that was largely inhibited by propranolol, indicating that hypotension per se was not responsible for the mobilization of Mg2+. Infusion of salbutamol, but not prenalterol, also induced an increase in circulating Mg2+. Pretreatment with butoxamine, ICI-118551, or propranolol prevented the ISO-induced increase in serum Mg2+. Pretreatment with atenolol minimally affected the ISO-induced changes in circulating Mg2+. Pretreatment with CGP-20271A actually enhanced the ISO-induced increase in circulating Mg2+. This evidence demonstrates the existence of a pool of Mg2+ that is mobilized into the circulation in response to selective beta 2-adrenergic stimulation.