Interactions of the systemic and brain renin-angiotensin systems in the control of drinking and the central mediation of pressor responses

Most of the biological actions of the circulating (a.k.a., the systemic or blood-borne) renin-angiotensin system require the generation of the octapep tide angiotensin (ANG) II from the decapeptide ANG I. In the case of circul ating ANG I, the lungs are generally considered the major site for this con version. The present experiments explored the possibility that under condit ions of marked elevations of blood-borne ANG I, the generation of ANG II ta kes place within brain-associated target tissues, most notably circumventri cular organs (CVOs) that lack a blood-brain barrier. The first important re sult of these experiments demonstrates that intracerebroventricular (i.c.v. ) infusion of the converting enzyme inhibitor, captopril, completely blocks the drinking response and significantly attenuates the presser response pr oduced by systemically infused ANG I. This result indicates that under phys iological/pathophysiological conditions associated with large elevations of circulating ANG I, an important part of the biological responses derived f rom blood-borne ANG may result from local conversion of ANG I to ANG II wit hin specific brain target tissues which have high concentrations of convert ing enzyme. This local conversion process provides an important mechanism t hat would act to reinforce the "classic" conversion process which takes pla ce in the lungs thereby delivering more ANG II immediately to central targe t receptors. The second important finding from these studies showed that dr inking produced by systemically infused ANG II was not attenuated by an i.c .v. dose of captopril which was effective in blocking a comparable dipsogen ic response induced by i.v. ANG I. This observation suggests that drinking induced by systemic ANG II does not require an intact metabolic cascade wit hin the brain for the formation of ANG II (or ANG II-like effector peptide) from ANG I. (C) 1999 Elsevier Science B.V. All rights reserved.