Changes of adrenomedullin and its receptor components mRNAs expression in the brain stem and hypothalamus-pituitary-adrenal axis of stress-induced hypertensive rats.

In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the changes in mRNAs levels of preproadrenomedullin (ppADM) gene encoding adrenomedullin (ADM) and the essential receptor components of ADM, calcitonin receptor-like receptor (CRLR), and the receptor activity modifying protein 2 and 3 (RAMP2 and RAMP3) in the medulla oblongata, hypothalamus, midbrain, pituitary gland and adrenal gland of the stress-induced hypertensive rats. It was shown that chronic foot-shock and noise stress for 15 consecutive days induced a significant increase in systolic blood pressure (SBP) and unique changes in ppADM and its receptor components mRNAs in all areas studied. As compared with the control group, the level of ppADM mRNA, normalized against a glyceraldehydes-3-phosphate dehydrogenase (GAPDH) control, was up-regulated in the hypothalamus-pituitary-adrenal (HPA) axis, but down-regulated in the medulla oblongata and midbrain (P<0.01 and P<0.05, respectively). The relative amount of CRLR mRNA was higher in the hypothalamus than that in other areas. The level of CRLR mRNA expression was significantly increased in the medulla oblongata of the stress group (P<0.01), but decreased in the midbrain (P<0.01) as well as hypothalamus(P<0.05), as compared with that of the control group. Chronic stress for 15 consecutive days produced an increase in the level of RAMP2 mRNA expression in the medulla oblongata (P<0.01) and a decrease in the adrenal gland (P<0.01), as compared with the control. No significant stress-related changes in RAMP2 mRNA were observed in the midbrain, hypothalamus and pituitary gland. The amount of RAMP3 mRNA was relatively higher in the midbrain and hypothalamus than that in the medulla oblongata, adrenal gland and adrenal gland. Stress-induced hypertensive rats exhibited an increased RAMP3 mRNA expression in the hypothalamus and pituitary gland (P<0.01 and P<0.05, respectively) and a decrease in the adrenal gland and midbrain (P<0.05). No significant stress-related change in RAMP3 mRAN was observed in the medulla oblongata. Taken together, our results indicate that the significant changes in ppADM and its receptor components mRNAs expression in the HPA axis and autonomic centers may be related to the development of the stress-induced hypertension. Nevertheless, the pathophysiological significance of brain-derived ADM and its receptors in stress and blood pressure regulation and their roles in stress-induced hypertension still await further investigation.