The role of Angiotensin II and Angiotensin (1-7) on the overflow of Neuropeptide Y and Norephinephrine in Spontaneously Hypertensive Rats.

摘要

Neuropeptide Y (NPY) is a cotransmitter with Norepinephrine (NE) and Adenosine Triphosphate 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 and maintenance of hypertension. Angiotensin II (Ang II) is known to facilitate sympathetic neurotransmission; an effect greater in Spontaneously Hypertensive Rats (SHR) than normotensive rats. A newly discovered product of the RAS is Angiotensin (1-7). There is evidence suggesting that Ang (1-7) opposes the hypertensive actions of Ang II. The objective of this study was to investigate the role of Ang II and Ang (1-7) on the nerve stimulated NE and NPY overflow from the mesenteric arterial bed of SHR.;Ang II increased the basal and nerve stimulated NPY overflow from the mesenteric bed; an effect that is greater in preparations of SHR than age matched normotensive controls. Preparations obtained from prehypertensive (4-6 week old) SHR appear to behave similarly to those of hypertensive (10-12 week old) SHR with respect to Ang II induced changes in nerve stimulated NPY overflow. This facilitatory effect of Ang II is mediated by the AT1 and the AT2 receptors. In addition, Captopril and the AT1 receptor antagonist EMD66684 decreased neurotransmitter overflow from SHR preparations, suggesting the presence of an active local RAS. In contrast, Ang (1-7) decreased nerve stimulated NE and NPY overflow from mesenteric arteries. This effect was greater in preparations of SHR than WKY. Administration of a Mas receptor antagonist, attenuated the Ang (1-7) induced decrease in NE and NPY overflow. However, the AT2 receptor antagonist attenuated the effect of Ang (1-7) on NE overflow, but not NPY overflow. Moreover, in the presence of L-NAME and Bradykinin B2 receptor antagonist, Ang (1-7) decreased NPY overflow but not NE overflow.;Ang (1-7) decreases, whereas Ang II enhances the nerve stimulated NE and NPY overflow from SHR preparations. Therefore, Ang (1-7) may counteract the effects of Ang II by acting on AT2 and Mas Receptors. In addition, our data suggests that Ang (1-7) modulates sympathetic neurotransmission through a nitric oxide dependent mechanism.