Kinin B₂ receptor localization and expression in the hypothalamo-pituitary-adrenal axis of spontaneously hypertensive rats

Objective: An enhanced hypothalamo-pituitary-adrenocortical (HPA) activity has been demonstrated during onset of high blood pressure in spontaneously hypertensive rats (SHR). Furthermore, compared to normotensive Wistar-Kyoto (WKY) rats, SHR show hypersensitivity to bradykinin (BK)-induced pressor responses which may be caused by an upregulation of B₂ receptor expression in the brain. Methods: We performed an immuohistochemical localization and measured gene expression of B₂ receptors in the hypothalamus, pituitary and adrenal glands of SHR at three ages corresponding to the development of hypertension, i.e. prehypertensive phase, onset of hypertension and established hypertension. Using reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot technique, B₂ receptor mRNA and protein levels, respectively, were measured. Results: A specific immunostaining for B₂ receptors was observed in the hypothalamic nuclei paraventricularis (PVN) and supraopticus (SON). In the pituitary and adrenal glands, a strong immunostaining was observed in neurohypophysis (NH) and adrenal medulla, respectively. At all ages tested, B₂ receptor mRNA and protein levels were higher in the hypothalamus and adrenal glands of SHR compared to age-matched WKY rats. Among SHR, the mRNA level was increased in neurohypophysis with age, and no difference was found in the adenohypophysis (AH) between SHR and WKY rats. Conclusion: The data demonstrate a specific localization and an upregulation of B₂ receptor expression in the hypothalamus and adrenal glands of SHR, providing an anatomical and molecular basis for a possible contributory role to bradykinin-induced hypersensitivity of cardiovascular responses. The increased B₂ receptor expression in the hypothalamus and adrenal glands may also play a role in the abnormalities of the HPA axis in SHR during the development of hypertension.