Adrenomedullin 2 attenuates the pressor but not adrenal responses to angiotensin II in conscious sheep.

Biological actions attributed to the adrenomedullin (AM) peptides, AM and AM2, include reduction of arterial pressure and peripheral resistance. While AM has been shown to reduce aldosterone secretion from the adrenal, little information is available regarding possible actions of AM2 on aldosterone. Evidence suggests that AM may act as a functional antagonist to angiotensin II (Ang II) but such a role has not been investigated for AM2. Accordingly, we have examined hemodynamic and adrenal responses to stepped Ang II infusions with or without co-infusions of AM2 (33ng/(kgmin)) in conscious sheep under controlled conditions of a low sodium intake. The dose-dependent pressor response (5-50mmHg) of Ang II was both delayed and attenuated (p<0.001) by AM2 which also stimulated heart rate (p<0.001) and cardiac output (p<0.001). AM2 prevented Ang II-induced increases in peripheral resistance (p<0.001). In contrast, plasma aldosterone responses to Ang II were not significantly altered by concomitant AM2 infusion. In conclusion, low dose infusion of AM2 administered to conscious sheep on a low salt diet clearly antagonized the vasopressor action of administered Ang II while stimulating cardiac output and heart rate. In contrast to AM, AM2 had no restraining influence on the aldosterone response to Ang II. The data suggest a possible role for AM2 in cardiovascular homeostasis in part through antagonism of the vasopressor action of Ang II.