A. Ratajska et al., ANGIOTENSIN-II ASSOCIATED CARDIAC MYOCYTE NECROSIS - ROLE OF ADRENAL CATECHOLAMINES, Cardiovascular Research, 28(5), 1994, pp. 684-690
Objective: Cardiac myocyte necrosis is associated with an endogenous i
ncrease in angiotensin II or a subpressor dose of angiotensin II. In e
ach case, raised plasma angiotensin II, together with aldosterone, res
ults in cardiac myocyte necrosis followed by scarring. Arterial hypert
ension is non-contributory. The aim of this study was to determine whe
ther myocyte necrosis is induced directly by angiotensin II, or indire
ctly by catecholamines or aldosterone released from adrenal glands in
response to angiotensin II. Methods: Right and left ventricular myocar
dium was examined over a two week period in rats receiving a subpresso
r yet cardiotoxic dose of angiotensin II (150 ng.min(-1).kg(-1) subcut
aneously) alone or together with total adrenalectomy, bilateral medull
ectomy, or the aldosterone receptor antagonist spironolactone (150-200
mg.d(-1).kg(-1)). Findings were compared to unoperated age/sex matche
d controls. Coronal sections obtained from the base, equator and apex
of the heart were stained with antifibronectin antibody to detect myoc
yte injury, picrosirius red for fibrillar collagen, or haematoxylin an
d eosin. Results: In both right and left ventricles (a) fibronectin la
belling was distributed within injured cardiac myocytes and adjacent i
nterstitium of both ventricles in rats receiving angiotensin II or ang
iotensin II plus spironolactone; (b) fibronectin labelling of myocytes
was markedly diminished or absent in the ventricles of rats with tota
l adrenalectomy or bilateral medullectomy; and (c) there was microscop
ic scarring of both ventricles after two weeks of either angiotensin I
I or angiotensin II plus spironolactone, but not in medullectomised or
adrenalectomised animals. Conclusions: In the presence of increased c
irculating levels of angiotensin II, bilateral medullectomy and total
adrenalectomy (in contrast to spironolactone) reduced myocyte injury a
nd scarring of the right and left ventricular myocardium, suggesting t
hat the cytotoxic effect of angiotensin II is largely indirect and rel
ated to circulating catecholamines released by the adrenal medulla.