Angiotensin 1–7 decreases nerve stimulated Norepinephrine (NE) and Neuropeptide Y (NPY) overflow from the mesenteric arterial beds of SHR

Abstract

NPY is a cotransmitter with NE and ATP in sympathetic nerves. There is evidence for increased activity of the sympathetic nervous system and the renin‐angiotensin system (RAS) as well as a role for NPY in the development of hypertension in experimental animal models and in humans. Angiotensin II (Ang II) is known to facilitate sympathetic neurotransmission; an effect greater in Spontaneously Hypertensive Rats (SHR) than normotensive Wistar‐Kyoto (WKY) rats. A newly discovered product of the RAS is the peptide Angiotensin 1–7 (Ang 1–7). There is evidence suggesting that Ang 1–7 opposes the actions of Ang II resulting in hypotensive effects. The objective of this study was to investigate the role of Ang 1–7 on the nerve stimulated overflow of NE and NPY from the mesenteric arterial bed of SHR and the receptors mediating any effects produced.Ang 1–7 (0.001, 0.01, 0.1μM) decreased nerve stimulated NE and NPY overflow, as well as perfusion pressure in preparations obtained from SHR. This effect was greater in preparations of SHR than WKY controls. Administration of the Mas Receptor Antagonist (MRA), D‐Ala Ang 1–7, and the Angiotensin Type 2 Receptor Antagonist (AT2A), PD12339 attenuated this effect.Ang 1–7 decreases the nerve stimulated overflow of NE and NPY in preparations of SHR, while Ang II enhances it. Therefore, Ang 1–7 may counteract the effects of Ang II by acting on AT2 and Mas Receptors. (Sponsored by NIH HL60260 and AHA)