VASCULAR INJURY AUGMENTS ADRENERGIC NEUROTRANSMISSION

Background We have observed persistent desensitization to exogenous no repinephrine after balloon injury. We postulated that this desensitiza tion may be due to a local increase in the release of neuronal norepin ephrine. Methods and Results New Zealand White rabbits underwent left iliac artery angioplasty; 4 weeks later, both iliac arteries were harv ested. Maximal response to exogenous norepinephrine was reduced in inj ured 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 i nduce neuronal norepinephrine release) was significantly greater in in jured tissues (36+/-7% versus 14+/-3%; values expressed as percent of maximal contraction to exogenous norepinephrine; P=.025). Direct measu rement of tissue norepinephrine revealed a threefold increase 4 weeks after injury (1236+/-410 versus 466+/-97 pg/mg; injured versus noninju red). To determine if desensitization to exogenous norepinephrine was due to a persistent increase in neuronal norepinephrine release, the e xperiments were repeated after chemical sympatholysis using 6-hydroxyd opamine (6-OHDA) (65 mg/kg). To determine if activation of vascular an giotensin II contributed to facilitation of adrenergic neurotransmissi on, other animals received ramipril (RAM; 1 mgikg per day). Both treat ments were initiated 7 days before angioplasty. In the 6-OHDA group th ere was no evidence of desensitization, judged by maximal response to exogenous norepinephrine (7.5+/-0.6 versus 7.5+/-0.8, noninjured versu s injured). Similar results were obtained in RAM animals (9.9+/-0.8 ve rsus 9.6+/-1.2, noninjured versus injured). Conclusions This is the fi rst study to demonstrate enhanced adrenergic neurotransmission after b alloon injury. The facilitation of adrenergic neurotransmission may be due to increased local concentrations of angiotensin II and is associ ated with desensitization to exogenous norepinephrine.