| 19926936 |
Martinez AC, Pagan RM, Prieto D, Recio P, Garcia-Sacristan A, Hernandez M, Benedito S: Modulation of noradrenergic neurotransmission in isolated rat radial artery. J Pharmacol Sci. 2009 Nov;111(3):299-311.
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. |
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