Vascular injury augments adrenergic neurotransmission

Robert C. Candipan, Paul T.C. Hsiun, Richard Pratt, John P. Cooke

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Background: We have observed persistent desensitization to exogenous norepinephrine after balloon injury. We postulated that this desensitization may be due to a local increase in the release of neuronal norepinephrine. Methods and Results: New Zealand White rabbits underwent left iliac artery angioplasty; 4 weeks later, both iliac arteries were harvested. Maximal response to exogenous norepinephrine was reduced in injured compared with noninjured vessels (12.3±1.0 g versus 10.3±1.5 g; n=7, P=.056). By contrast, response to electrical stimulation (to induce neuronal norepinephrine release) was significantly greater in injured tissues (36±7% versus 14±3%; values expressed as percent of maximal contraction to exogenous norepinephrine; P=.025). Direct measurement of tissue norepinephrine revealed a threefold increase 4 weeks after injury (1236±410 versus 466±97 pg/mg; injured versus noninjured). To determine if desensitization to exogenous norepinephrine was due to a persistent increase in neuronal norepinephrine release, the experiments were repeated after chemical sympatholysis using 6-hydroxydopamine (6-OHDA) (65 mg/kg). To determine if activation of vascular angiotensin II contributed to facilitation of adrenergic neurotransmission, other animals received ramipril (RAM; 1 mg/kg per day). Both treatments were initiated 7 days before angioplasty. In the 6-OHDA group there was no evidence of desensitization, judged by maximal response to exogenous norepinephrine (7.5±0.6 versus 7.5±0.8, noninjured versus injured). Similar results were obtained in RAM animals (9.9±0.8 versus 9.6±1.2, noninjured versus injured). Conclusions: This is the first study to demonstrate enhanced adrenergic neurotransmission after balloon injury. The facilitation of adrenergic neurotransmission may be due to increased local concentrations of angiotensin II and is associated with desensitization to exogenous norepinephrine.

Original languageEnglish (US)
Pages (from-to)777-784
Number of pages8
JournalCirculation
Volume89
Issue number2
DOIs
StatePublished - Feb 1994

Keywords

  • angioplasty
  • angiotensin
  • norepinephrine
  • restenos

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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