Angiotensin-(1-7) modulates vascular resistance and sympathetic neurotransmission in kidneys of spontaneously XXXX @entity35 .

@entity101 @entity35 @entity1809 @entity1808 @entity1811 @entity1063
OBJECTIVE: Angiotensin (Ang)-(1-7) generated from @entity1808 is reported to act as an endogenous @entity1811 ( @entity1811 ) inhibitor and angiotensin type 1 ( @entity1809 )-receptor antagonist in vitro and in vivo. Ang-(1-7) has been suggested to play an important role in @entity101 . METHODS AND RESULTS: Therefore, we tested whether Ang-(1-7) differentially modulates vascular resistance and neurotransmission in isolated kidneys of spontaneously @entity101 @entity35 stroke prone (SHR-SP) and @entity35 -Kyoto @entity35 (WKY). Ang-(1-7) was administered in three concentrations (0.1, 1 and 10 micromol/l) to prevent Ang I- and Ang II-induced pressor responses and facilitation of @entity1063 release. There were indeed concentration-dependent strain differences. Ang-(1-7) prevented Ang I- and Ang II-mediated changes in vascular resistance more potently in SHR-SP than in WKY by inhibiting @entity1811 and by blocking @entity1809 -receptors. Ang-(1-7) by itself had no influence on renal vascular tone in both strains. Ang-(1-7) inhibited Ang I-mediated facilitation of @entity1063 release more potently than Ang II-mediated facilitation of @entity1063 release. Ang-(1-7) by itself enhanced @entity1063 release from SHR-SP, but not from WKY kidneys. CONCLUSION: Ang-(1-7) had a greater impact on Ang I and Ang II modulation of renal vascular resistance in SHR-SP than in normotensive @entity35 . Furthermore, Ang-(1-7) by itself has facilitatory presynaptic effects on @entity1063 release but no postsynaptic effects on renal vascular resistance in SHR-SP. Since plasma levels of Ang-(1-7) accumulate during @entity1811 -inhibitor or @entity1809 -receptor antagonist therapy, Ang-(1-7) could contribute to antihypertensive effects of these agents.
