Comparative actions of adrenomedullin and nitroprusside: interactions with ANG II and norepinephrine

The role of adrenomedullin (ADM) in volume and pressure homeostasis remains undefined. Accordingly, we compared the biological responses to infusions of ADM and nitroprusside (NP; matched for reduction of arterial pressure) and assessed their effects on responses to ANG II and norepinephrine in eight conscious sheep. During matched falls in arterial pressure (8-10 mmHg, both P < 0.001) ADM and NP induced similar increases in heart rate. ADM increased cardiac output (P < 0.001), and the fall in calculated peripheral resistance was greater with ADM than NP (P = 0.013). ADM infusions raised plasma ADM levels (P < 0.001), plasma renin activity (P = 0.001), and ANG II (P < 0.001) but tended to blunt any concurrent rise in aldosterone compared with NP (P = 0.056). ADM maintained both urine flow (P < 0.001) and sodium excretion (P = 0.01) compared with falls observed with NP. ADM attenuated the vasopressor actions of exogenous ANG II (P = 0.006) but not norepinephrine. In addition, ADM antagonized the ANG II-induced rise in plasma aldosterone (P < 0.001). In conclusion, ADM induces a different spectrum of hemodynamic, renal, and endocrine actions to NP. These results clarify mechanisms by which ADM might contribute to volume and pressure homeostasis.