FREQUENCY-DEPENDENT AND TRAIN LENGTH-DEPENDENT VARIATION IN THE ROLES OF POSTJUNCTIONAL ALPHA-1-ADRENOCEPTOR AND ALPHA-2-ADRENOCEPTOR FOR THE FIELD STIMULATION-INDUCED NEUROGENIC CONTRACTION OF RAT TAIL ARTERY

The present paper examines the roles of postjunctional alpha1- and alpha2-adrenoceptors for the noradrenaline (NA)-induced neurogenic contractile response to field stimulation mainly with 1 - 100 pulses at 2 or 20 Hz, in the tail artery of adult normotensive rats. Pharmacological tools were employed to isolate and characterize the alpha1- and alpha2-adrenoceptor-mediated components of this response. The degree to which the drugs influenced NA release or reuptake was assessed by their effects on the electrochemically determined, stimulation-induced rise in the NA concentration at the innervated outer surface of the media. This response was unaffected by alpha,beta-methylene ATP (10 muM) or suramin (500 muM), added to desensitize or block P2-purinoceptors, respectively prazosin (0.1 muM) or SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxyl]-3-methyl-1H-2,3,4,5-tetrohydro-3-benzazepine, 0.1 muM), used to block postjunctional alpha1- and alpha2-adrenoceptors respectively, nifedipine (10 muM), blocker of Ca2+ influx through L-type channels, and ryanodine (10 muM), which blocks mobilization of Ca2+ from intracellular stores; it was moderately enhanced by yohimbine (0.1 muM), blocker of pre- and postjunctional alpha2-adrenoceptors, and strongly enhanced by cocaine (3 muM) or desipramine (1 muM), blockers of NA reuptake. Judging from their inhibitory effects on the contractile responses to the alpha1- and alpha2-adrenoceptor agonists, phenylephrine and xylazine, prazosin (0.1 muM) and SK & F 104078 (0.1 muM) could be used to selectively block alpha1- and alpha2-adrenoceptors respectively, while yohimbine (0.1 muM) was less selective, strongly depressing alpha2- and slightly depressing alpha1-adrenoceptor-mediated responses. The alpha1-adrenoceptor-mediated component of the contractile response to short trains at 20 Hz was fast in onset, brief in duration and abolished by ryanodine; that mediated by alpha2-adrenoceptors was more delayed, prolonged and insensitive to ryanodine. Both components were dose-dependently depressed by nifedipine (0.1 - 10 muM). The small contractile responses to single pulses, or up to 50 pulses at 2 Hz, or short train (< 4 pulses) at 20 Hz, were more markedly depressed by 0.1 muM yohimbine or SK & F 104078 than by 0.1 muM prazosin and, hence, mediated mainly by a2-adrenoceptors. The reverse was true of the much larger response to longer trains at 20 Hz, which thus probably was mediated mainly by alpha1-adrenoceptors. Cocaine or desipramine, as well as alpha,beta-methylene ATP or suramin, amplified both components of the NA-induced contractile response especially that mediated via alpha-adrenoceptors and caused by single pulses or short trains. The main conclusions are (i) that the small NA-induced contractile responses of this artery to single pulses, or pulses at low frequency, or in short trains at high frequency, are mediated mainly via alpha2-, and the larger responses to longer trains at high frequency increasingly via alpha1-adrenoceptors, (ii) that the alpha1- and alpha2-adrenoceptor-mediated components interact cooperatively, probably at least in part by utilizing two different pathways to increase the intracellular Ca2+, (iii) that neuronal reuptake of NA strongly restricts both components of the NA-induced contraction, especially the alpha1-adrenoceptor-mediated response to single pulses or short trains, and (iv) that both components of the NA-induced contraction, especially that mediated by alpha1-adrenoceptors, may be depressed by ATP released by field stimulation and acting via P2x-purinoceptors on smooth muscle. Based on these results a novel working hypothesis is proposed, in which it is assumed that the geometry of NA-mediated neuromuscular transmission in this vessel varies with the frequency and number of impulses in a stimulus train.