Differential effects of angiotensin II and angiotensin-(1-7) at the nucleus tractus solitarii of transgenic rats with low brain angiotensinogen.
OBJECTIVE
In this study, we investigated the effects of angiotensin II and angiotensin-(1-7) at the nucleus tractus solitarii (nTS) in transgenic rats with a severe deficit in brain angiotensinogen production, TGR(ASrAOGEN) (TGR).


METHODS
Angiotensin II (10 pmol), angiotensin-(1-7) (10 pmol) or NaCl (0.9%/50 nl) were microinjected into the nTS of urethane-anaesthetized TGR (n = 36) and Sprague Dawley (SD) (n = 34) rats. Mean arterial pressure (MAP) and heart rate were measured via a femoral artery catheter and the baroreflex control of heart rate was evaluated after increases in MAP induced by phenylephrine (baroreflex bradycardia).


RESULTS
Angiotensin II microinjections into the nTS of the TGR induced a higher decrease in MAP and heart rate (-37 +/- 5 mmHg and -69 +/- 12 b.p.m., respectively) in comparison to SD rats (-18 +/- 1 mmHg and -43 +/- 5 b.p.m., respectively). In contrast, changes after angiotensin-(1-7) microinjections into the nTS of TGR (-6 +/- 1 mmHg and -13 +/- 4 b.p.m.) were significantly smaller than that induced in SD (-11 +/- 2 mmHg and -24 +/- 6 b.p.m.). The baseline baroreflex sensitivity to phenylephrine of TGR was accentuated in comparison to SD rats (0.70 +/- 0.06 versus 0.44 +/- 0.03 ms/mmHg). Angiotensin II microinjection into the nTS produced similar attenuation in the baroreflex bradycardia in both SD (0.28 +/- 0.07 versus 0.5 +/- 0.07 ms/mmHg, before injection) and TGR (0.44 +/- 0.1 versus 0.82 +/- 0.1 ms/mmHg, before injection). In contrast, angiotensin-(1-7) microinjection elicited a facilitation of the baroreflex bradycardia in SD (0.68 +/- 0.12 versus 0.41 +/- 0.03 ms/mmHg, before injection), while in TGR, angiotensin-(1-7) induced an attenuation of baroreflex bradycardia (0.34 +/- 0.07 ms/mmHg versus 0.55 +/- 0.05 ms/mmHg, before injection).


CONCLUSIONS
These results indicate that a permanent inhibition of angiotensinogen synthesis in the brain can lead to an increase in the sensitivity of the baroreflex control of heart rate (baroreflex bradycardia) and an increase in angiotensin II responsiveness at the nTS. However, the nTS effect of angiotensin-(1-7) was significantly attenuated in these transgenic rats. These data further indicate that the decrease in brain angiotensins in the transgenic rats may be functionally relevant and support the concept of differential regulatory mechanisms for the effects of the two angiotensin peptides.
Couto
Aurea S
AS
Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Baltatu
Ovidiu
O
Santos
Robson A S
RA
Ganten
Detlev
D
Bader
Michael
M
Campagnole-Santos
Maria J
MJ
D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000808:Angiotensinogen / Q000172:deficiency*; D000818:Animals; D030801:Animals, Genetically Modified; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism*; D002319:Cardiovascular System / Q000187:drug effects; D006339:Heart Rate; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology; D008845:Microinjections; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D017552:Solitary Nucleus / Q000187:drug effects*
D010446:Peptide Fragments; D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)