Angiotensin peptides acting at rostral ventrolateral medulla contribute to hypertension of TGR(mREN2)27 rats.
We have previously demonstrated that microinjections of the selective angiotensin-(1-7) [ANG-(1-7)] antagonist, A-779, into the rostral ventrolateral medulla (RVLM) produces a significant fall in mean arterial pressure (MAP) and heart rate (HR) in both anesthetized and conscious rats. In contrast, microinjection of angiotensin II (ANG II) AT(1) receptor antagonists did not change MAP in anesthetized rats and produced dose-dependent increases in MAP when microinjected into the RVLM of conscious rats. In the present study, we evaluated whether endogenous ANG-(1-7) and ANG II acting at the RVLM contribute to the hypertension of transgenic rats harboring the mouse renin Ren-2 gene, TGR(mREN2)27. Unilateral microinjection of A-779 (0.1 nmol) produced a significant fall in MAP (-25 +/- 5 mmHg) and HR (-57 +/- 20 beats/min) of awake TGR rats. The hypotensive effect was greater than that observed in Sprague-Dawley (SD) rats (-9 +/- 2 mmHg). Microinjection of the AT(1) antagonist CV-11974 (0.2 nmol) produced a fall in MAP in TGR rats (-14 +/- 4 mmHg), contrasting with the pressor effect observed in SD rats (33 +/- 9 mmHg). These results indicate that endogenous ANG-(1-7) exerts a significant pressor action in the RVLM, contributing to the hypertension of TGR(mREN2)27 transgenic rats. The role of ANG II at the RVLM seems to be dependent on its endogenous level in this area.
Fontes
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MA
Laboratório de Hipertensão, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte MG, Brazil.
Baltatu
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Caligiorne
S M
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Campagnole-Santos
M J
MJ
Ganten
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Bader
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Santos
R A
RA
D000803:Angiotensin I / Q000008:administration & dosage / Q000378:metabolism*; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D008845:Microinjections; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics*; D013777:Tetrazoles / Q000008:administration & dosage
C092006:7-Ala-angiotensin (1-7); D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010446:Peptide Fragments; D013777:Tetrazoles; D000804:Angiotensin II; D000803:Angiotensin I; D012083:Renin; C118790:angiotensin I (1-7); C081643:candesartan