ANGIOTENSIN-II ASSOCIATED CARDIAC MYOCYTE NECROSIS - ROLE OF ADRENAL CATECHOLAMINES

Objective: Cardiac myocyte necrosis is associated with an endogenous increase in angiotensin II or a subpressor dose of angiotensin II. In each case, raised plasma angiotensin II, together with aldosterone, results in cardiac myocyte necrosis followed by scarring. Arterial hypertension is non-contributory. The aim of this study was to determine whether myocyte necrosis is induced directly by angiotensin II, or indirectly by catecholamines or aldosterone released from adrenal glands in response to angiotensin II. Methods: Right and left ventricular myocardium was examined over a two week period in rats receiving a subpressor yet cardiotoxic dose of angiotensin II (150 ng.min(-1).kg(-1) subcutaneously) alone or together with total adrenalectomy, bilateral medullectomy, or the aldosterone receptor antagonist spironolactone (150-200 mg.d(-1).kg(-1)). Findings were compared to unoperated age/sex matched controls. Coronal sections obtained from the base, equator and apex of the heart were stained with antifibronectin antibody to detect myocyte injury, picrosirius red for fibrillar collagen, or haematoxylin and eosin. Results: In both right and left ventricles (a) fibronectin labelling was distributed within injured cardiac myocytes and adjacent interstitium of both ventricles in rats receiving angiotensin II or angiotensin II plus spironolactone; (b) fibronectin labelling of myocytes was markedly diminished or absent in the ventricles of rats with total adrenalectomy or bilateral medullectomy; and (c) there was microscopic scarring of both ventricles after two weeks of either angiotensin II or angiotensin II plus spironolactone, but not in medullectomised or adrenalectomised animals. Conclusions: In the presence of increased circulating levels of angiotensin II, bilateral medullectomy and total adrenalectomy (in contrast to spironolactone) reduced myocyte injury and scarring of the right and left ventricular myocardium, suggesting that the cytotoxic effect of angiotensin II is largely indirect and related to circulating catecholamines released by the adrenal medulla.