Modulation of noradrenergic neurotransmission in isolated rat radial artery

J Pharmacol Sci. 2009 Nov;111(3):299-311. doi: 10.1254/jphs.09135fp.

Abstract

The present study was designed to characterize the neurogenic contraction of rat radial artery. Electrical field stimulation (EFS) evoked frequency-dependent contraction that was abolished by tetrodotoxin (neuronal Na(+) channel blocker), guanethidine (sympathetic neuron blocker), or phentolamine (alpha-adrenoceptor blocker). The alpha(1)-adrenoceptor antagonist prazosin inhibited endothelium-independent contractions to EFS, noradrenaline (NA), and the alpha(1)-adrenoceptor agonist phenylephrine. Rauwolscine, an alpha(2)-adrenoceptor antagonist, augmented nerve-mediated contractions and reduced sensitivity to NA and the alpha(2)-adrenoceptor agonist BHT-920. The beta-adrenoceptor antagonist propranolol diminished EFS-elicited contractions, while sensitivity to NA was enhanced by propranolol. Relaxations evoked by isoproterenol, a beta-adrenoceptor agonist, were abolished by propranolol. N(G)-Nitro-L-arginine (L-NOARG), a nitric oxide (NO) synthase inhibitor, increased both nerve-mediated and NA-induced responses in endothelium-intact, but not in endothelium-denuded arteries. Moreover, endothelium-dependent responses to BHT-920 and isoproterenol were modified by L-NOARG. Tetraethylammonium (TEA) or 4-aminopyridine, the Ca2+-activated (K(Ca)) or voltage-dependent K+ (K(V)) channel blockers, respectively, enhanced the neurogenic contractions observed. TEA but not 4-aminopyridine increased NA-induced contractions. The ATP-sensitive K+ (K(ATP))-channel blocker glibenclamide failed to modify adrenergic contractions. Blockade of capsaicin-sensitive primary afferents increased EFS-induced contractions. In conclusion, adrenergic contractions are predominantly mediated by muscular alpha(1)-adrenoceptors, while endothelial alpha(2)- and beta-adrenoceptors play a minor role. Presynaptic alpha(2)- and beta-adrenoceptors cannot be precluded. Noradrenergic neurotransmission in rat radial artery seems to be modulated by both stimulation of endothelial NO, K(Ca), and K(V) channels and sensory C-fiber activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Capsaicin / pharmacology
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Neurons, Afferent / drug effects
  • Nitric Oxide / metabolism
  • Norepinephrine / physiology*
  • Potassium Channels / drug effects
  • Radial Artery / innervation
  • Radial Artery / physiology*
  • Rats
  • Rats, Wistar
  • Sensory Receptor Cells / drug effects
  • Synaptic Transmission / physiology*
  • Vasoconstriction / physiology

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Potassium Channels
  • Nitric Oxide
  • Capsaicin
  • Norepinephrine