Effects of extracellular magnesium and beta adrenergic stimulation on contractile force and magnesium mobilization in the isolated rat heart.
This study investigates the metabolism of the divalent cation, magnesium (Mg2+) in the isolated perfused Langendorff's rat heart and ventricular slices in the absence and presence of catecholamines including isoprenaline, noradrenaline and adrenaline. Perfusion of the isolated rat heart with a physiological salt solution containing elevated extracellular Mg2+ [Mg2+]o (2.4 mM-6.0 mM) resulted in a marked and progressive decrease in the amplitude of contraction compared to control [Mg2+]o (1.2 mM). In contrast, perfusion of hearts with low (0-0.6 mM) [Mg2+]o caused a small transient increase in the amplitude of contraction which was often accompanied by arrhythmic activity. Perfusion of the heart with a nominally Mg2+ free medium resulted in a time-dependent net efflux of Mg2+ reaching a steady state after approximately 40-50 min of perfusion. This release of Mg2+ was associated with a concurrent decrease in total heart Mg2+. Stimulation of the heart with the beta adrenergic agonist, isoprenaline (10(-7) M) caused large increases in net Mg2+ efflux which was associated with marked increased in both rate and the amplitude of contraction. Similar effects on Mg2+ efflux were also observed during perfusion of the heart with the adenylate cyclase activator, forskolin (10(-5) M). Superfusion of paced ventricular segments with either isoprenaline, adrenaline or noradrenaline (all 10(-6) M) also resulted in a marked transient net efflux of Mg2+. Pre-treatment of segments with the beta adrenergic antagonist, propranolol (10(-5) M) competitively blocked the Mg2+ efflux evoked by the catecholamines. Similarly, pre-treatment of segments with the calcium (Ca2+) channel blocker, verapamil (10(-5) M) caused a significant (P < 0.05) decrease in net Mg2+ efflux evoked by isoprenaline. The results of this study indicate that (1) the perturbation of [Mg2+]o has an important influence on myocardial contractility and (2) the mobilization of Mg2+ in the heart is associated with beta adrenergic stimulation possibly via an elevation in intracellular adenosine 3.5 cyclic monophosphate (cyclic AMP).
Howarth
F C
FC
Department of Applied Biology, University of Central Lancashire, Preston, England, UK.
Waring
J
J
Hustler
B I
BI
Singh
J
J
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013054:Spectrophotometry, Atomic; D014700:Verapamil / Q000494:pharmacology
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D014700:Verapamil; D000242:Cyclic AMP; D008274:Magnesium; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine