Activation of a renin-angiotensin system in ischemic cardiac sympathetic nerve endings and its association with norepinephrine release Academic Article uri icon

Overview

MeSH Major

  • Biopsy, Fine-Needle
  • Melanoma
  • Skin Neoplasms

abstract

  • We had reported that in the ischemic heart, locally formed bradykinin (BK) and angiotensin II (Ang II) activate B2- and AT1-receptors on sympathetic nerve terminals (SNE), promoting reversal of the norepinephrine (NE) transporter in an outward direction (i.e., carrier-mediated NE release). Although both BK and Ang II contribute to ischemic NE release, Ang II is likely to play a more important role. Since BK is formed by ischemic SNE, we questioned whether cardiac SNE also contribute to local Ang II formation, in addition to being a target of Ang II. SNE were isolated from surgical specimens of human right atrium and incubated in ischemic conditions. These SNE released large amounts of endogenous NE via a carrier-mediated mechanism, as evidenced by the inhibitory effect of desipramine on this process. Moreover, two renin inhibitors, pepstatin-A and BILA 2157 BS, the ACE inhibitor enalaprilat and the AT1-receptor antagonist EXP3174 prevented ischemic NE release. Western blot analysis revealed the presence of renin in cardiac SNE. Renin abundance increased more than three-fold during ischemia. Thus, renin is present in cardiac SNE and is activated during ischemia, eventually culminating in Ang II formation, stimulation of AT1-receptors and carrier-mediated NE release. Our findings uncover a novel autocrine mechanism, by which Ang II, formed at SNE in myocardial ischemia, elicits carrier-mediated NE release by activating prejuntional AT1-receptors.

publication date

  • December 2002

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/S1567-5769(02)00148-0

Additional Document Info

start page

  • 1965

end page

  • 73

volume

  • 2

number

  • 13-14