Angiotensin-(1-7) and baroreflex function in nucleus tractus solitarii of (mRen2)27 transgenic rats

Background: Endogenous angiotensin (Ang)-(1-7) enhances, while Ang 11 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 11 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-Ala 7)-Ang-(1-7). Results: (mRen2) 27 rats exhibited a similar to 50% impairment in BRS as compared with SD (P < 0.05). (D-Ala 7)-Ang-(1-7) attenuated BRS by similar to 50% in SD rats, but was without effect in (mRen2) 27 rats. (DAla 7)-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, neptilysin, or the mas receptor in medullary tissue from SD versus (mRen2)27 rats. Conclusion: 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.