N005: Changes in left ventricular adrenomedullin gene expression in pressure overload by angiotensin II in rats in vivo

• Published in: American journal of hypertension Vol. 13; no. S2; p. 308A
• Main Authors: Földes, G., deChâtel, R., Szokodi, I., Lakó-Futó, Z., Ruskoaho, H., Tóth, M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2000
• Subjects: adrenalectomy; Adrenomedullin; angiotensin II; cardiac hypertrophy
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(00)01101-8

Adrenomedullin (AM), a vasodilative, antiproliferative and positive inotropic peptide may play a regulative role in cardiovascular homeostasis. However, stimuli and time course of its activation remain unclear. We studied the effect of pressure overload induced by angiotensin II (AII) on AM production in the left ventricles (LV) of rats in vivo. Male SD rats were treated with continuous infusions of AII in a pressure-elevating dose (33 μg/kg/h) for 12 or 72 hours. In order to dissect the relative roles of cardiac and plasma AM, which is thought to have the major source from the adrenal glands, the experiments were done in intact and also in adrenalectomized (Adx) rats. AII has elevated mean blood pressure averaged at 40 mmHg, as proven by in vivo telemetry. AII was also found to be a potent agent elevating LV/body weight ratio (mean ± SEM, AII: 2.57 ± 0.02; sham: 2.25 ± 0.02, P < 0.001) at 72 h. Northern analysis revealed that AII induced at 12 hours 1.4-fold AM gene expression, and 3.6-fold ANP gene expression, which was used as a biological marker for cardiac hypertrophy. AM plasma peptide level was also increased by AII and changes were more prominent at 12 as at 72 hours (AII: 48.2 ± 4.4; sh: 19.7 ± 1.1 fmol/ml at 12 h, P < 0.05). Interestingly, Adx elevated basal and AII-induced changes in plasma AM indicating that in this model the adrenals are not the only determinant of plasma AM. Our results therefore indicate that AM is involved in the early endocrine changes in the course of cardiac hypertrophy induced by angiotensin II. Plasma-born or locally produced AM can serve as a protective mechanism in cardiac hypertrophy.