Role of adrenomedullin and its receptor system in renal pathophysiology.

Adrenomedullin (AM), a potent vasorelaxing, natriuretic and cell growth-modulating peptide, is thought to act as an autocrine/paracrine regulator in renal glomeruli and tubules. AM receptors comprise the calcitonin receptor-like receptor (CRLR) and a family of receptor-activity-modifying proteins (RAMPs 1-3); however, the pathophysiological role of AM and its receptor system in the kidney remains to be clarified. We examined the regulation of their expression in a rat model of renal injury and found that RAMP1, RAMP2 and CRLR expressions were markedly upregulated upon induction of fibrosis during obstructive nephropathy. Since AM exerts potent antiproliferative effects in various cell types, upregulation of the AM receptor system may play important roles in modulating the progression of renal diseases.