Vascular injury augments adrenergic neurotransmission.

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.

Attenuated inhibition of adrenergic contraction by nitric oxide in injured guinea pig femoral artery

“…The diminished response to NA in injured arteries at a late period (I8) is in accordance with findings of a previous study with balloon-injured rabbit FA [34]. As suggested in that study [34], elevated tissue catecholamine levels could be causative of the diminished response to NA we noted in I8.…”

The balloon catheter induces an increase in contralateral carotid artery reactivity to angiotensin II and phenylephrine

“…This effect may be the consequence of an increased production of inducible nitric oxide in the ipsilateral vessel wall, as suggested by several studies (Major et al, 1985;Joly et al, 1992;Douglas et al, 1994;Hansson et al, 1994). The decreased response to Phe could also be related to the desensitisation to exogenous ligands (Candipan et al, 1994), to a decrease in a1-adrenoceptors from day 3 up to 10 weeks after injury (Bruijns et al, 1998) or increased production of inducible nitric oxide in injured vessel (Major et al, 1985;Joly et al, 1992;Douglas et al, 1994;Hansson et al, 1994;Yan & Hansson, 1998).…”

Effects of Chemical Sympathectomy on Angiotensin II-Induced Neointimal Growth in the Balloon-Injured Rat Carotid Artery

“…One possible explanation may be the increased exposure of the vessel to neurogenic and circulating catecholamines after balloon injury that may downregulate α 1 -adrenoceptors. Indirect evidence for this possibility is provided in the rabbit iliac artery injury model where the increase in local facilitation of adrenergic neurotransmission after injury resulted in decreased contractile responses to exogenous catecholamines [38]. However, in contrast to β 2 -adrenoceptors, α 1 -adrenoceptors have been reported to be rather resistant to homologous downregulation [39].…”