Elsevier

Life Sciences

Volume 65, Issue 21, 15 October 1999, Pages 2241-2249
Life Sciences

Regulation of cardiac adrenomedullin-mRNA in different stages of experimental heart failure

https://doi.org/10.1016/S0024-3205(99)00489-0Get rights and content

Abstract

Adrenomedullin (AM) is a peptide hormone with vasodilating and natriuretic properties. AM plasma concentrations are elevated in heart failure. Whether cardiac AM-mRNA synthesis is increased in heart failure is not known. We measured AM-mRNA/GAPDH-mRNA in all four heart chambers in compensated and overt heart failure in rats with two different sizes of aortocaval shunt. Left and right atrial AM-mRNA expressions were unchanged in both heart failure models. Similarly, left and right ventricular AM-mRNA expressions were unchanged in compensated heart failure. In overt heart failure, however, the AM-mRNA expression was significantly increased in the left ventricle (145 ± 20 vs. 100 ±3 % of control, p < 0.05). The right ventricular AM-mRNA expression was significantly increased only in a subgroup of animals with pulmonary congestion (lung weight > 2.0 g, 141 ± 16 vs. 100 ± 11 % of control, p < 0.05). Ventricular AM concentrations were elevated in both ventricles in overt heart failure. AM plasma concentrations were significantly higher in the subgroup with pulmonary congestion than in rats with compensated heart failure (496 ± 95 vs. 143 ± 7 pmol/l, p < 0.01). These data indicate that ventricular AM-mRNA expression and AM concentrations were upregulated only in advanced stages of heart failure. However, the exact contribution of cardiac AM synthesis to the increased AM plasma levels remains to be established.

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      AM concentration decreased in the left atrium of renovascular hypertension [28] and in volume overloaded atria in rats [32], possibly due to the release from the intracellular stores of atrial cardiac myocytes. Atrial AM mRNA and concentration did not change in the failing hearts of rats, dogs, and humans, compared with that in the heart of controls [34,38,39]. The stimulatory G protein-adenylate cyclase-cAMP to activate protein kinase A is a major pathway that increases cardiac contractility [40].

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