Adrenergic and ischaemic challenge on the activities of lipid metabolising enzymes in the perfused rat heart.

Abstract

This investigation was undertaken to study the effects of adrenergic and ischaemic challenge on the activity of lipid metabolising enzymes in the perfused rat heart. Perfusion with adrenaline or the beta agonist isoprenaline produced an increase in triglyceride lipase (TGL) activity and a fall in glycerol 3-phosphate acyltransferase (GPAT) activity. No change was seen in carnitine palmitoyl transferase (CPT) activity. These changes could be imitated by incubation of heart homogenates with cAMP-dependent protein kinase. The non-selective alpha agonist phenylephrine, and the alpha2 agonist clonidine produced the opposite affect, a fall in TGL activity and a rise in GPAT activity. Methoxamine, an alpha1, had no affect on TGL activity but reduced GPAT activity. Changes in GPAT activity were localized mainly in the microsomal fraction. The changes in TGL and GPAT activity are consistant with both enzymes being regulated via a cyclic AMP-dependent protein kinase system and via alpha adrenergic mechanisms. Ischaemia was produced by occlusion of the left descending coronary artery for 10 minutes. Compared to activities measured in tissue from normally perfused hearts, GPAT activity measured in tissue from the ischaemic area was considerably reduced while TGL activity in the ischaemic area was markedly increased. No change was seen in GPAT or TGL activity measured in tissue from the non-ischaemic area or in CPT activity measured in both areas. The changes in activities produced by ischaemia were prevented by pre-perfusion with the cardio-selective beta antagonist Atenolol. Reperfusion of the ischaemic area resulted in TGL activity returning to the value measured in tissue from normally perfused hearts. However, GPAT activity, after 1 minute of reperfusion, fell to a value lower than after 10 minutes ischaemia. This reperfusion-induced fall in GPAT activity was prevented by pre-perfusion with the alpha1 antagonist Doxasozin. Pre-perfusion of the alpha2 antagonist Yohimbine resulted in a prolongation of the increased TGL activity in the ischaemic area during reperfusion. All changes in enzyme activities were prevented when endogenous noradrenaline stores were depleted by injection of 6 OH-dopamine 24 hours before hearts were removed. These changes in enzyme activities show that during ischaemia there is an increased beta-adrenergic drive. On reperfusion the beta-adrenergic drive is removed but an alpha1 adrenergic drive becomes apparent.

Date of Award	1985
Original language	English
Awarding Institution	University of Bath