. Roles of adrenomedullin 2 in regulating the cardiovascular and sympathetic nervous systems in conscious rats. Am J Physiol Heart Circ Physiol 290: H1120 -H1127, 2006. First published October 14, 2005; doi:10.1152/ajpheart.00461.2005.-Recently, a new member of the calcitonin gene-related peptide (CGRP) family, adrenomedullin 2 (AM2) or intermedin (IMD), was identified. AM2/ IMD has been shown to have a vasodilator effect in mice and rats and an effect on urine formation in rats. In the present study, we investigated the effects of intravenously infused rat AM2 (rAM2) on blood pressure (BP), heart rate (HR), renal sympathetic nerve activity (RSNA), and renal blood flow (RBF) in conscious unrestrained rats relative to the effects of rat adrenomedullin (rAM) and proadrenomedullin NH 2-terminal 20 peptide (rPAMP). Intravenous infusion of rAM2 (5 nmol/kg) significantly decreased BP and increased HR, RSNA, and RBF. These hypotensive and sympathoexcitatory effects diminished after 20 min, and HR returned to control levels 30 min after cessation of the infusion. In contrast, a significant increase in RBF was still evident 60 min after cessation of the peptide infusion. The duration of BP, HR, and RSNA responses was longer with rAM (5 nmol/kg) than with rAM2 infusion, whereas the increases in RBF induced by rAM2 and rAM were similar in their amplitude and duration. Infusion of rPAMP (200 nmol/kg) increased HR and RSNA but had no effect on RBF. Baroreceptor denervation suppressed, but did not diminish, the increases in HR and RSNA to rAM2. These findings indicate that the physiological roles of rAM2 and rAM are similar and that rAM2 also has a long-lasting vasodilator action on the renal vascular bed.hemodynamics; sympathetic outflow; vasodilation ADRENOMEDULLIN (AM), a potent 52-amino acid vasodilator, was originally isolated from tissue extracts of human pheochromocytoma (15). AM is a multifunctional peptide that exhibits various actions, such as cardiovascular, renal, and respiratory regulation, as well as central nervous system regulation and regulation of other hormone secretions (2,10,12,16,21,28). AM has also been implicated in various disease states, such as heart failure and renal dysfunction (1,7,9,14,17,18,20). Recently, a new member of the calcitonin generelated peptide (CGRP) family, adrenomedullin 2 (AM2) or intermedin (IMD), was identified (23, 26). Administration of AM2/IMD decreased blood pressure (BP) in mice and rats (23,26), and this effect was partially blocked by AM and CGRP receptor antagonists (23). Takei et al. (26) reported AM2 expression in the kidneys, lungs, gastrointestinal system, thymus, and brain. Most recently, Taylor et al. (27) demonstrated that IMD protein immunoreactivity was present in plasma, as well as in heart, lungs, kidneys, stomach, pituitary gland, and brain. These findings suggest that AM2/IMD is present in various organs of mammals and that AM2/IMD may have physiological effects similar to those of AM and CGRP.Intrarenal infusion of human AM2 decreased BP in a dosedepende...