Effects of Adrenoceptor Blockade on Cardiac Hypertrophy and Myocardial Phospholipids

Abstract

Catecholamines have been proposed as a stimulus for the hypertrophic response to pressure overload of the heart and could also mediate the membrane lipid changes associated with cardiac hypertrophy. To address both of these possibilities, cardiac hypertrophy was induced by aortic constriction in the presence or absence of chronic alpha- or beta-adrenoceptor blockade. Heart weights and heart weight to body weight ratios in aortic-constricted rats of the adrenoceptor-blocked and vehicle-treated groups were elevated to the same extent when compared with values in sham-operated rats of each group. Analysis of the fatty acyl composition of the major phospholipid classes revealed that similar changes occurred in vehicle-treated, alpha-blocked, and beta-blocked aortic-constricted rats when compared with respective groups of sham-operated rats. Specifically, linoleic acid was reduced in the phosphatidylcholine, phosphatidylethanolamine (PE), and cardiolipin (CL) fractions in all groups of aortic-constricted rats. This reduction was accompanied by increased docosahexaenoic acid, arachidonic acid, or palmitic acid in phosphatidylcholine; docosahexaenoic acid in phosphatidylethanolamine; and oleic acid in cardiolipin fractions. Adrenoceptor blockade did not prevent or attenuate the major changes in the fatty acyl composition of phospholipids or the increase in heart weight associated with aortic constriction. This suggests that a change in the level of adrenoceptor stimulation is not the stimulus for cardiac hypertrophy or the observed alterations in phospholipid composition in the pressure-overloaded rat heart.

Change in the Membranous Lipid Composition Accelerates Lipid Peroxidation in Young Rat Hearts Subjected to 2 Weeks of Hypoxia Followed by Hyperoxia

“…There was also a concomitant increase in n-3 PUFA, which was mainly related to C22:6 in total lipids and PE. This finding is similar to previous reports of the fatty acid composition of cardiac phospholipids in membrane lipids in adolescents animals exposed to high doses of catecholamines, 19 aortic constriction 20 or intermittent high altitude hypoxia. 21 Although exposure to chronic hypoxia is initially associated with an increase in adrenergic activity, 22,23 adrenoceptor blockade does not attenuate the changes in the fatty acid composition of phospholipids.…”

“…21 Although exposure to chronic hypoxia is initially associated with an increase in adrenergic activity, 22,23 adrenoceptor blockade does not attenuate the changes in the fatty acid composition of phospholipids. 20 In our preliminary study, the fatty acid composition of hypoxic rat hearts followed by 2 weeks ofnormoxia was not remarkably different in the comparison with that of normoxic rat hearts (data not shown). We believe from these results that the change in fatty acid composition after 2 weeks of hypoxic exposure is reversible by re-establishing a normoxic environment.…”

“…13 Hypoxia is associated with an increase in adrenergic activity, 20,21 which may be responsible for the reduction in body weight.…”

Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure

“…Early evidence of CL alterations in the failing heart come from studies conducted by O'Rourke, Reibel, and colleagues (42,43), who reported a reduction in the BW, final body weight; sham, animals euthanized at 4 weeks after sham TAB surgery; TAB, animals euthanized at 1 week after thoracic aortic banding surgery; TAB1HS, animals fed an 8% NaCl diet for 3 weeks after a 1 week recovery from TAB surgery. Data are presented as means 6 SEM.…”

Cardiolipin Remodeling in the Heart

“…The earliest evidence of CL's role in heart failure was a reduction of the linoleate content of the cardiac CL pool in rats that were induced to pressure overload hypertrophy by chronic aortic banding. 129,130 In spontaneously hypertensive heart failure rat hearts, temporal studies were carried out that followed tetralinoleoyl CL throughout the stages of the animals' pathology. 131 These animals develop early hypertension, followed by cardiac hypertrophy, and heart failure resulting in decompensated hypertrophy, pulmonary congestion, and death at 21-24 months of age.…”