Angiotensin II/NaCl Increases FosB Expression in the Paraventricular and Supraoptic Nucleus

Abstract

The purpose of the present study is to examine changes in FosB immunohistochemistry evoked by an in vivo hypertension model, angiotensin II/high salt diet (ANGII), within the supraoptic nucleus (SON) and paraventricular nucleus of the hypothalamus (PVN). Immuno‐detection of Fos, a member of the AP‐1 family of transcription regulatory proteins, has been widely used as an indicator of neural activation. FosB is an inducible member of the Fos family that has been proposed to be a marker of chronic activation in the central nervous system, and increases in Fos expression have been shown to occur under several pathophysiological conditions. Angiotensin II and a high salt diet have been proposed to activate several brain regions involved in autonomic function. As such, we used FosB to determine the changes in neuronal activity in the forebrain of ANGII treated rats as compared to rats treated with high salt diet only, and rats on a normal diet (control group). By examining the changes in FosB, we can determine which hypothalamic brain regions are being chronically modulated by the ANGII model. For further comparison, we also measured changes in FosB in ANGII hypertensive rats treated with a kappa opioid receptor (KOR) agonist, which has been shown to produce effects on cardiovascular and renal function. Male Sprague‐Dawley rats were instrumented with osmotic mini‐pumps filled with angiotensin II for subcutaneous (s.c.) infusion. In addition, rats were implanted with an ICV cannula for delivery of drugs into the lateral cerebral ventricle. After recovering, rats were fed 2% high salt diet for 14 days and at day 15, injected with either U50‐488H, kappa opioid receptor agonist, or saline. Ninety minutes post injection, each rat was anesthetized with Inactin (100 mg/kg i.p.) and perfused with PBS and fixative [4% paraformaldehyde in phosphate buffered saline, PBS, pH =7.4]. The brains were removed and processed for FosB immunocytochemistry using a commercially available antibody (1:1000 rabbit anti‐FosB). Brain sections were examined using light microscope to identify FosB positive cells. ANGII hypertensive model increased FosB expression in the PVN when compared to high salt diet. ANGII also increase FosB expression in the PVN and SON when compared to naïve‐control rats. Although FosB expression increased in the PVN, there were no statistically significant changes in FosB expression between magnocellular and parvocellular region. U50‐488H administration decreased FosB expression in the SON and PVN. The PVN and SON have been shown to be involved in the control of blood pressure, fluid and electrolyte balance. Central KOR receptor inhibition of these forebrain regions may form part of the neuropathways involved in the decreases in water and sodium excretion evoked by KOR activation.