Summary
Microinjection of noradrenaline or phenylephrine into the nucleus locus coeruleus of cats induced a dose dependent and long lasting hypotension. Clonidine was required in a dose of 1 μg for eliciting a significant hypotension while its lower doses (up to 500 ng) failed to elicit any significant cardiovascular alteration. The effects on heart rate evoked by these agents were insignificant. Microinjection of α-adrenoceptor antagonists prazosin, piperoxan and RX 781094 per se did not evoke any significant cardiovascular effects and only prazosin pretreatment showed dose dependent antagonism of the hypotensivee effect of clonidine. Piperoxan was required in four times higher dose (20 μg) to partially antagonize the clonidine induced hypotension. RX 781094, a selective α2-adrenoceptor antagonist, however, even up to a dose of 20 μg (four times that of prazosin) did not alter the effect of clonidine. Similar pattern of antagonism was also seen for noradrenaline and phenylephrine. The results demonstrate the presence of α1-adrenoceptors in the nucleus locus coeruleus, the activation of which leads to a fall in blood pressure.
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References
Ader JP, Postema F, Korf J (1979) Contributions of the locus coeruleus to the adrenergic innervation of the rat spinal cord: a biochemical study. J Neural Transmission 44:159–173
Bhargava KP, Jain IP, Saxena AK, Sinha JN, Tangri KK (1978) Central adrenoceptors and cholinoceptors in cardiovascular control. Br J Pharmacol 63:7–15
Cambridge D, Davey MJ, Massingham R (1977) The pharmacology of antihypertensive drugs with special reference to vasodilators α-adrenergic blocking drugs and prazosin. Med J Aust (2 suppl) 1:2–6
Chapelo CB, Doxey JL, Myers PL, Roach AG (1981) RX 781094. A new potent, selective antagonist of α2-adrenoceptors. Br J Pharmacol 74:842P
Commissioning JW, Hellstrom SO, Neff NH (1978) A new projection from locus coeruleus to the spinal ventral columns: histochemical and biochemical evidence. Brain Res 148:207–213
Dahlstrom A, Fuxe K (1965) Evidence for the existence of monoamine neurones in the central nervous system. Acta Physiol Scand [64 suppl] 246:1–85
Debire H, Mouille P, Andrejak M, Fournier B, Schmitt H (1981) Pre- and post-synaptic α-adrenoceptor blockade by (imidazolinyl-2-)-2-benzodioxane 1–4 (170150). Antagonistic action on central effects of clonidine. Arch Int Pharmacodyn 254:262–270
DeJong W (1974) Noradrenaline: Central inhibitory control of blood pressure and heart rate. Eur J Pharmacol 29:179–181
Dettmar PW, Lynn AG, Tulloch IF (1981) Neuropharmacological evaluation of RX 781094 a new selective α-adrenoceptor antagonist. Br J Pharmacol 74:843P
Gunn CG, Sevelius G, Puiggari J, Myers FK (1968) Vagal cardioinhibitory mechanisms in the hind brain of the dog and cat. Am J Physiol 214:258–262
Gurtu S, Sinha JN, Bhargava KP (1982a) Receptors in the medullary cardioinhibitory loci. I. Nucleus tractus solitarius: Catecholaminergic modulation of baroreflex induced bradycardia. Ind J Pharmacol 14:37
Gurtu S, Sinha JN, Bhargava KP (1982b) Involvement of α-adrenoceptors of the nucleus tractus solitarius in baroreflex mediated bradycardia. Naunyn-Schmiedeberg's Arch Pharmacol 321:38–43
Gurtu S, Sharma DK, Sinha JN, Bhargava KP (1983) Evidence of the involvement of α2-adrenoceptors in the nucleus ambiguus in baroreflex mediated bradycardia. Naunyn-Schmiedeberg's Arch Pharmacol 323:199–204
Gurtu S, Pant KK, Sinha JN, Bhargava KP (1984) Mechanism of the cardiovascular effects evoked by electrical stimulation of nucleus locus coeruleus and subcoeruleus in the cat. Brain Res 301:59–64
Guyenet PG (1980) The coeruleospinal noradrenergic neurones: Anatomical and electrophysiological studies in the rat. Brain Res 189:121–133
Hannah JAM, Hamilton CA, Reid JL (1983) RX 781094, a new potent α2-adrenoceptor antagonist. In vivo and in vitro studies in the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 322:221–227
Jacobowitz D, Kostrzewa R (1971) Selective action of 6-hydroxydopa on noradrenergic terminals: Mapping of preterminal axons of the brain. Life Sci 10:1329–1342
Kawamura H, Gunn CG, Frohlich CD (1978) Cardiovascular alteration by nucleus locus coeruleus in spontaneously hypertensive rat. Brain Res 140:137–147
Kobayashi RM, Palkovits M, Jacobowitz DM, Kopin IJ (1975) Biochemical mapping of the noradrenergic projection from the locus coeruleus. Neurology 25:223–233
Kostowski W (1975) Interaction between serotonin and catecholaminergic systems in brain. J Pharmacol [suppl] 27:15–24
Kubo T, Misu Y (1981) Pharmacological characterization of the α-adrenoceptors responsible for a decrease in blood pressure in the nucleus tractus solitarius of the rat. Naunyn-Schmiedeberg's Arch Pharmacol 317:120–125
Langer SZ (1978) Modern concepts of adrenergic transmission. In: Legg NI (ed) Neurotransmitter systems and their clinical disorders. Academic Press, New York, pp 29–51
Langer SZ (1980) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362
Loewy AD, Neil JJ (1980) A role of descending monoaminergic systems in central control of blood pressure. Fed Proc 40:2778–2785
Loizou LA (1969) Projections of the nucleus locus coeruleus in the albino rat. Brain Res 15:563–566
Maeda T, Shimuju M (1972) Projections ascendantes du locus coeruleus et d'autres neuronen aminergiques pontiques au niveau du prosencephale du rat. Brain Res 36:19–35
Maruyama S (1981) Inhibition by topically applied clonidine and guanfacine of the pressor response to stimulation of the locus coeruleus in cats. Jap J Pharmacol 31:586–589
Nygren LG, Olson L (1977) A new major projection from the locus coeruleus: the main source of noradrenergic nerve terminals in the venttral and dorsal columns of the spinal cord. Brain Res 132:85–93
Olson L, Fuxe K (1972) Further mapping out of central noradrenaline systems: Projections of the subcoeruleus area. Brain Res 43:289–295
Pant KK, Gurtu S, Sharma DK, Sinha JN, Bhargava KP (1983) Cardiovascular effects of microinjection of morphine into the nucleus locus coeruleus in the cat. Jap J Pharmacol 33:253–256
Philippu A, Demmeler R, Roensberg G (1974) Reduced blood-pressure response to locus coeruleus stimulation. Naunyn-Schmiedeberg's Arch Pharmacol 282:389–400
Pickel VM, Joh TH, Reis DJ (1977) A serotonergic innervation of NA neurones in nucleus locus coeruleus: Demonstration by immunohistochemical localization of the transmitter specific enzymes tyrosine and tryptophan hydroxylase. Brain Res 131:197–214
Przuntek H, Philippu A (1973) Reduced pressor responses to stimulation of the locus coeruleus after lesion of the posterior hypothalamus. Naunyn-Schmiedeberg's Arch Pharmacol 276:119–122
Ross RA, Reis DJ (1974) Effects of lesions of locus coeruleus on regional distribution of dopamine β-hydroxylase activity in rat brain. Brain Res 73:161–166
Sakai K, Touret M, Salbert D, Leger L, Jouvet M (1977) Afferent projections to the cat locus coeruleus as visualised by the horseradish peroxidase technique. Brain Res 119:21–41
Sharma DK, Gurtu S, Sinha JN, Bhargava KP (1982) Receptors in the medullary cardioinhibitory loci. II. Nucleus ambiguus: Changes in heart rate and blood pressure following microinjection of adrenergic and cholinergic agents. Ind J Pharmacol 14:38
Sharma DK (1982) Further analysis of the central receptors involved in the baroreceptor reflex. Thesis for M. D. (Pharmacology) University of Lucknow, India
Sinha JN, Tangri KK, Bhargava KP, Schmitt H (1975) Central sites of sympatho-inhibitory effects of clonidine and l-dopa. International symposium on hypertension, Monte Carlo, Monaco. In: Milliez P, Safar M (eds) Recent advances in hypertension, vol 1. Boehringer-Ingelheim, Reims, pp 97–109
Sinha JN, Gurtu S, Bhargava KP (1981) Effects of microinjection of α-adrenoceptor agonists and antagonist into medullary cardioinhibitory loci. Proceedings of the VIII International Conference of IUPHAR, Tokyo, Japan. Abstract 374
Sinha JN, Gurtu S, Sharma DK, Bhargava KP (1982a) An investigation of the α-adrenoceptors of the nucleus ambiguus involved in the regulation of heart rate. Naunyn-Schmiedeberg's Arch Pharmacol [Suppl] 319:R47
Sinha JN, Gurtu S, Bhargava KP (1982b) Characterization of the receptors of the nucleus tractus solitarius (NTS) involved in regulation of heart rate. Neurosci Abstr [Suppl] 7:S 195
Shimiju N, Imamoto K (1970) Fine structure of the locus coeruleus in the rat. Arch Histol Jap 31:229–246
Snider RS, Niemer WT (1961) A stereotaxic atlas of cat brain. The University of Chicago Press
Starke K, Montel H, Gayk W, Merker R (1974) Comparison of the effects of clonidine and pre and post-synaptic adrenoceptors in the rabbit pulmonary artery: α-sympathomimetic inhibition of neurogenic vasoconstriction. Naunyn-Schmiedeberg's Arch Pharmacol 285:133–150
Starke K, Endo T, Taube HD (1975) Relative pre and post-synaptic potencies of α-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn-Schmiedeberg's Arch Pharmacol 291:55–78
Svensson TH, Bunney BS, Aghajanian GK (1975) Inhibition of both noradrenergic and serotonergic neurones in brain by the α-adrenergic agonist clonidine. Brain Res 92:291–306
Ward DG, Baertschi AJ, Gann DS (1975) Activation of solitary nucleus neurones from the locus coeruleus and vicinity. Neurosci Abstr p 658
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Sinha, J.N., Sharma, D.K., Gurtu, S. et al. Nucleus locus coeruleus: Evidence for α1-adrenoceptor mediated hypotension in the cat. Naunyn-Schmiedeberg's Arch. Pharmacol. 326, 193–197 (1984). https://doi.org/10.1007/BF00505317
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DOI: https://doi.org/10.1007/BF00505317