Modulation of noradrenergic neurotransmission in isolated rat radial artery.
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.
Martínez
Ana Cristina
AC
Department of Physiology, Faculty of Pharmacy, Complutense University, Spain.
Pagán
Rosa María
RM
Prieto
Dolores
D
Recio
Paz
P
García-Sacristán
Albino
A
Hernández
Medardo
M
Benedito
Sara
S
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D017534:Radial Artery / Q000294:innervation / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects; D009435:Synaptic Transmission / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D015221:Potassium Channels; D009569:Nitric Oxide; D002211:Capsaicin; D009638:Norepinephrine