Type 2 corticotropin-releasing hormone receptor mRNA expression in the heart in hypertensive rats

Novel subtype of corticotropin-releasing hormone receptor (CRHR), designated type-2 CRHR (CRHR-2), mRNA was expressed not only in the central nervous system but also in the peripheral tissues such as the heart and skeletal muscle. The previous finding that type-1 CRHR mRNA is not detected in heart leads us to speculate that systemic administration of CRH induces hypotensive effects through CRHR-2, and that alterations in CRHR-2 in the heart may be implicated in blood pressure regulation. Therefore we examined CRHR-2 mRNA expression in the heart (at the level of ventricle) in spontaneously hypertensive rats (SHR) or DOCA-salt hypertensive rats (DOCA) using in situ hybridization histochemistry, compared to age-matched normotensive control rats. CRHR-2 mRNA levels in the heart were significantly higher in 7-week-old SHR than in 12-week-old SHR. Furthermore, CRHR-2 mRNA levels in SHR heart were significantly higher than those in normotensive controls, Wistar-Kyoto rats (WKY), at both 7 and 12 weeks of age. In contrast, CRHR-2 mRNA levels in DOCA heart were significantly lower than that of sham-operated controls after 6-weeks of treatment. Thus, alterations of CRHR-2 mRNA are dependent on the strain or experimental condition rather than as a consequence of hypertension. Plasma CRH levels in SHR or DOCA were not different from their normotensive control rats. CRH content in the ventricular heart of SHR or DOCA were also similar to normotensive controls. These results suggest that heart CRHR-2 mRNA levels are not influenced by circulating or locally existing CRH. Since alterations in heart CRHR-2 mRNA, as seen in SHR and DOCA, were bi-directional, the role of heart CRHR-2 in the regulation of hypertension remains to be elucidated.