Angiotensin-(1-7) and baroreflex function in nucleus tractus solitarii of (mRen2)27 transgenic rats.
BACKGROUND
Endogenous angiotensin (Ang)-(1-7) enhances, while Ang II attenuates, baroreceptor sensitivity (BRS) for reflex control of heart rate (HR) in Sprague-Dawley (SD) rats. In (mRen2)27 renin transgenic rats [(mRen2)], there is overexpression of the mouse Ren2 gene in brain, leading to elevated Ang II and reduced Ang-(1-7) in brain medullary, and associated with hypertension and impaired BRS.


METHODS
We therefore tested the contribution of endogenous Ang-(1-7) to BRS for control of HR and responses to cardiac vagal chemosensitive afferent fiber activation (CVA) with phenylbiguanide (PBG) in anesthetized SD and (mRen2) 27 rats before and after bilateral nucleus of the solitary tract (nTS) injection of the Ang-(1-7) receptor antagonist (D-Ala7)-Ang-(1-7).


RESULTS
(mRen2) 27 rats exhibited a approximately 50% impairment in BRS as compared with SD (P < 0.05). (D-Ala7)-Ang-(1-7) attenuated BRS by approximately 50% in SD rats, but was without effect in (mRen2) 27 rats. (D-Ala7)-Ang-(1-7) did not alter the responses to CVA by PBG (iv bolus) in either strain. There were no differences in the depressor effects of Ang-(1-7) injected into the nTS, nor were levels of mRNA different for angiotensin-converting enzyme, angiotensin-converting enzyme 2, neprilysin, or the mas receptor in medullary tissue from SD versus (mRen2)27 rats.


CONCLUSIONS
Endogenous Ang-(1-7) does not provide tonic input in the nTS to modulate BRS for control of HR in (mRen2)27 rats, which may contribute to impairment of BRS in these animals.
Diz
Debra I
DI
Hypertension & Vascular Research Center, Division of Surgical Sciences, Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032, USA. ddiz@wfubmc.edu
Garcia-Espinosa
Maria Antonia
MA
Gallagher
Patricia E
PE
Ganten
Detlev
D
Ferrario
Carlos M
CM
Averill
David B
DB
D000803:Angiotensin I / Q000502:physiology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects*; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*
C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D001645:Biguanides; D010446:Peptide Fragments; C473112:Ren2 protein, mouse; D000804:Angiotensin II; D010656:Phenylephrine; D000803:Angiotensin I; D012083:Renin; C118790:angiotensin I (1-7); C008846:phenyl biguanide