Alterations of the renin-angiotensin system at the RVLM of transgenic rats with low brain angiotensinogen.
The transgenic rats TGR(ASrAOGEN) (TGR) with low levels of brain angiotensinogen 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 ventrolateral medulla (RVLM) of conscious rats. Microinjection of ANG II resulted in a significantly higher increase in the mean arterial pressure (MAP) of TGR than control [Sprague-Dawley (SD)] rats, suggesting an upregulation of ANG 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 role of AT(1) receptors in the RVLM. On the other hand, ANG-(1--7) appears to have a tonic excitatory role in this region. The altered response to specific angiotensin antagonists in TGR further supports the functionally relevant decrease in angiotensins in the brains of TGR and corroborates the importance of the central renin-angiotensin system in cardiovascular homeostasis.
Baltatu
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Max Delbrück Center for Molecular Medicine, D-13092 Berlin-Buch, Germany. baltatu@mdc-berlin.de
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D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000808:Angiotensinogen / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D007839:Functional Laterality; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010446:Peptide Fragments; D013777:Tetrazoles; D000808:Angiotensinogen; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; C081643:candesartan