Electrophysiological analysis of adrenergic neurotransmission and its modulation by chronic denervation in canine saphenous veins.
The present experiments were undertaken to investigate the electrophysiological responses of the canine saphenous vein evoked by perivascular nerve stimulation, norepinephrine or selective alpha adrenergic agonists before and after chronic sympathetic denervation. Unilateral sympathectomy was performed from T12 to L9 in adult female dogs. After 3 to 5 weeks, the denervated saphenous veins were removed. Innervated saphenous veins were obtained from unoperated dogs. In innervated but not in denervated veins, electrical stimulation generated excitatory junction potentials and a slow depolarization. The slow depolarization was inhibited by rauwolscine or phentolamine, but not by prazosin, whereas excitatory junction potentials were not inhibited by alpha adrenergic blockers. Exogenously applied norepinephrine caused a depolarization of the membrane that was inhibited by rauwolscine but not by prazosin. The selective alpha-1 adrenergic agonist, phenylephrine, and the selective alpha-2 adrenergic agonist, UK 14,304, caused depolarization. In denervated veins, the threshold concentrations of norepinephrine or UK 14,304 required to depolarize the smooth muscle cell membrane were reduced. Responses to phenylephrine were not affected by denervation. These results indicate that in the canine saphenous vein norepinephrine, whether added exogenously or released from sympathetic nerves, causes predominant depolarization by activating alpha-2 adrenergic receptors. Denervation augments selectively the electrical response to alpha-2 adrenergic stimulation.
Komori
K
K
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota.
Flavahan
N A
NA
Miller
V M
VM
Vanhoutte
P M
PM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D009121:Muscle Denervation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D012501:Saphenous Vein; D009435:Synaptic Transmission / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D009638:Norepinephrine; D011224:Prazosin