Differential Effects of Angiotensin II and Aldosterone on Cardiovascular Hypertrophy.

Abstract

The objective of this study was to determine the relative importance of angiotensin II (Ang II) and aldosterone in cardiovascular hypertrophy. Rats were given an infusion of Ang II (200 ng/kg/min) subcutaneously for 8 weeks with a mini-osmotic pump, with or without oral spironolactone (200 mg/kg) or MK-954 (30 mg/kg) daily. Ang II infusion resulted in marked hypertension of around 207 mmHg, which was associated with cardiac hypertrophy, with a heart-to-body-weight ratio of 0.35 ± 0.005% and thoracic aorta medial thickness of 0.166 ± 0.005 mm (vs. 0.285 ± 0.002% and 0.113 ± 0.003 mm, respectively, in control rats). Concomitant administration of spironolactone or MK-954 reduced the blood pressure in rats given Ang II to the same degree (164 and 171 mmHg, respectively). Aldosterone receptor blockade by spironolactone prevented Ang II-induced cardiac hypertrophy (heart-to-body-weight ratio = 0.307 ± 0.009% , but the Ang II-receptor antagonist MK-954 did not (heart-to-body-weight ratio = 0.331 ± 0.007%), although aortic vascular wall thickening in rats given Ang II was attenuated by both drugs. Renal hypertrophy induced by Ang II was not completely normalized by either drug. These results suggest that blockade of mineralocorticoid receptors is more effective than antagonism of Ang II receptors in preventing cardiac hypertrophy, and is as effective as antagonism of Ang II receptors in reducing vascular medial hypertrophy. They also indicate that, in addition to Ang II, aldosterone may play a pivotal role in regulating the growth of cardiac myocytes and vascular smooth muscle cells during Ang II-dependent hypertension. (Hypertens Res 1994; 17 233-237)

Aldosterone-Induced Organ Damage: Plasma Aldosterone Level and Inappropriate Salt Status

“…The Ang II-induced organ damage in this experimental model was inhibited by spironolactone (17). Plasma aldosterone levels in Ang II-treated rats were about 5.4 times higher than those seen in control rats, suggesting the intervention of the effects of aldosterone with excess salt, although these plasma aldosterone levels were markedly lower than those seen in former experimental models (6)(7)(8).…”

“…Robert et al reported that cardiac fibrosis induced by aldosterone with a high-salt diet can be inhibited not only by the MR antagonist, but also by an Ang II type 1 (AT1) receptor antagonist (ARB), suggesting the possible involvement of Ang II via the AT1 receptor in aldosterone actions via nonepithelial MR (14). ed by spironolactone (17). These reports strongly suggest that the "circulating" aldosterone is closely related, at least in part, to the organ damage directly induced by Ang II under salt loading, although the details remain obscure due to the lack of comparison with experiments under low-salt intake.…”

Eplerenone: A Selective Aldosterone Receptor Antagonist (SARA)

“…In addition to the classical epithelial actions, aldosterone binds to MR in nonepithelial tissues, such as the heart, brain, and blood vessels, where it is capable of mediating several pathophysiological actions (2,15,26,28,(46)(47)(48)50,51). For example, aldosterone has been reported to mediate hypertension in rats via central nervous system actions (21,22,57), and lead to stroke (42), malignant nephrosclerosis (42,43), cardiac fibrosis (49,55), ventricular hypertrophy (14,25,54), and myocardial necrosis (45).…”