Binding of angiotensin and atrial natriuretic peptide in brain of hypertensive rats

Abstract

Atrial natriruretic peptides, produced in the mammalian cardiac atrium, are released into the general circuhtion and may be actively invotved in the control of blood pressure and in fluid homeostasis as antagonists of the peripheral angiotensin systemri. Certain cardiovascular efrects of strial natriurctic peptides may be centrally mediated, as binding sites for atrial natriuretic factor (8-33) (ANF) h¡ye been localized to the subfornicel organs, This circumventricul¡r structu¡e lacLs a blood-b¡ai¡ barrie¡ and is therefore accessible to circulating p€ptides. It contains large numbers of angiotensin II (AII) binding sites, and hrs been suggested as the main central site of action for circulation -{II in the regulat¡o! of blood pressure and fluid m€tabolism67. He¡e we have studied bitrding sites for rat ¡tri¡l n¡triuretic peptide(6-33) (ÍANP) and AII in the brains of spontaneously (genetic) hypertensive rats (SHR) ¡nd their normotedsive controls, Wistar Kyoto (wKY) rats3, by quantitatiye autoradiographys'Lrr. atnding aites fo¡ both peptides were highly localized in the subfornical crgan. The ¡umberof rANP binditrg sitesw¡s decre¡sed in th€ subfornic¡l organ of both young (4 ryeeks old) and adult (14 rye€ks old) SHR compared with age-matched normotetsive controls. Conversely, the number of AII binding sites was h¡gher in both young ¡nd adult SHR compared with WKY rats. Our results suggest a central role for rANP and AII in genetic hypertension; they may act as mutual antagonists in br¡in a¡eas involved in coÍt¡ol of blood pressure a¡d fluid regulation. rANP closely resembles rat