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 (200ng/kg/min) subcutaneously for 8 weeks with a mini-osmotic pump, with or without oral spironolactone (200mg/kg) or MK-954 (30mg/kg) daily. Ang II infusion resulted in marked hypertension of around 207mmHg, 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±0.005mm (vs. 0.285±0.002% and 0.113±0.003mm, 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 171mmHg, 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)