Parasympathetic muscarinic stimulation limits noradrenaline induced myocardial creatine kinase release: a study in the isolated perfused working rat heart.
It has long been known that high concentrations of catecholamines may induce myocardial damage, and aggravate ischaemic injury. It has also been shown that beta-blockade may protect the myocardium from ischaemic damage. Stimulation of muscarinic receptors modulates beta-adrenergic receptor affinity for isoproterenol and attenuates isoproterenol induced adenylyl cyclase activation. Effects of muscarinic receptor stimulation were therefore investigated in isolated anterogradely perfused rat hearts under different experimental conditions. One group of hearts was perfused with noradrenaline, 10(-6) mol l-1 for 45 min, and another group was perfused with different carbachol concentrations (3 x 10(-7)-10(-5) mol l-1) with or without noradrenaline 10(-6) mol l-1, for 45 min. Release of creatine kinase to the perfusion buffer was taken as a sign of cell damage. Heart rate, left ventricular maxdP/dt and left ventricular pressure were measured throughout the perfusion time by insertion of a 20 gauge cannula through the left ventricular wall near the base. Carbachol (3 x 10(-7) mol l-1) alone induced a decrease of heart rate by 25% and maxdP/dt by 13%. Noradrenaline produced a 20% increase in heart rate, whereas the combination of noradrenaline plus carbachol induced a minor decrease in heart rate. Muscarinic receptor stimulation alone decreased myocardial contractility. However, when combined with noradrenaline no decrease in contractility was seen. Also, the release of creatine kinase to the perfusion buffer containing the combination of carbachol plus noradrenaline was reduced. Thus, muscarinic receptor stimulation protected the myocardium from catecholamine induced damage at concentrations where no change in contractility was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Waldenström
A
A
Department of Cardiology, University Hospital, University of Uppsala, Sweden.
Martinussen
H J
HJ
Kock
J
J
Ronquist
G
G
Hultman
J
J
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*
D011976:Receptors, Muscarinic; D002217:Carbachol; D000242:Cyclic AMP; D003402:Creatine Kinase; D009638:Norepinephrine