Alterations of the renin-angiotensin system at the RVLM of transgenic ratswith low brain angiotensinogen

The transgenic rats TGR(ASrAOGEN) (TGR) with low levels of brain angiotensi nogen were analyzed for cardiovascular reactivity to microinjections of ANG II and angiotensin receptor (AT(1)) antagonists [CV-11974, AT(1) specific; A-779, ANG(1-7) selective; sarthran, nonspecific] into the rostral ventrol ateral medulla (RVLM) of conscious rats. Microinjection of ANG II resulted in a significantly higher increase in the mean arterial pressure (MAP) of T GR than control [Sprague-Dawley (SD)] rats, suggesting an upregulation of A NG II receptors in TGR. CV-11974 produced an increase in MAP of SD but not in TGR rats. A-779 produced a depressor response in SD but not in TGR rats. Conversely, sarthran produced a similar decrease of MAP in both rat groups . The pressor effect of the AT(1) antagonist may indicate an inhibitory rol e of AT(1) receptors in the RVLM. On the other hand, ANG-(1-7) appears to h ave a tonic excitatory role in this region. The altered response to specifi c angiotensin antagonists in TGR further supports the functionally relevant decrease in angiotensins in the brains of TGR and corroborates the importa nce of the central renin-angiotensin system in cardiovascular homeostasis.