Receptor activity modifying protein 2 distribution in the rat central nervous system and regulation by changes in blood pressure

The neuropeptide, adrenomedullin, acts in the central nervous system (CNS) to regulate blood pressure, at least partly through an adrenomedullin receptor which is composed of receptor activity modifying protein 2 (RAMP-2) and calcitonin receptor-like receptor (CRLR). We used in situ hybridization to localize RAMP-2 mRNA throughout the brain, and we performed reverse transcription-polymerase chain reaction to detect CRLR mRNA in the brain. We found that RAMP-2 mRNA is expressed in numerous areas, including autonomic nuclei such as the paraventricular, supraoptic, arcuate and ventromedial nuclei, as well as the nucleus of the solitary tract (NTS), area postrema and dorsal motor nucleus of the vagus. Many regions expressing RAMP-2 mRNA also express low levels of CRLR mRNA. We examined changes in the mRNA expression of RAMP-2 and preproadrenomedullin in the brain in response to blood pressure manipulations. Rats received intravenous infusions of nitroprusside or phenylephrine to decrease or increase blood pressure, respectively. Decreased blood pressure elicited an increase in RAMP-2 mRNA expression in the NTS and a decrease in preproadrenomedullin mRNA expression in the paraventricular nucleus (PVN). Increased blood pressure elicited a decrease in RAMP-2 mRNA expression in the PVN and NTS. The CNS distribution and modulation of adrenomedullin signalling components by changes in blood pressure provide anatomical and physiological evidence for a homeostatic role for adrenomedullin in the brain.