Summary
Neuropeptide Y (NPY), neurotensin, arginine vasopressin (AVP), angiotensin II (ANG II), atrial natriuretic peptide (ANP) and calcitonin gene-related peptide (CGRP) have been suggested as putative neurotransmitters in the nucleus tractus solitarii (NTS) where baro- and chemoreceptor afferents terminate. To investigate modulation of the aortic baroreceptor reflex by neuropeptides, we microinjected these neuropeptides into the medial area of the rat NTS and examined their effects on the depressor and bradycardic responses to electrical stimulation of the aortic nerve which contains mainly baroreceptor afferent fibers in rats. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. NPY (3 ng) and neurotensin (0.3 ng) injected into the NTS caused a decrease in blood pressure and/or heart rate, and facilitated the depressor and bradycardic responses to aortic nerve stimulation. AVP (3 ng) produced an increase in blood pressure and heart rate, and inhibited the responses to aortic nerve stimulation, whereas d(CH) 5Tyr(Me)AVP (100 ng), a V1 vasopressin receptor antagonist, did not affect the basal cardiovascular parameters and the baroreflex responses. ANG 11(0. 3 and 3 ng) caused a decrease in blood pressure and heart rate whereas at 0.3 ng it did not affect the baroreflex responses. ANP (3 ng) and CGRP (3 ng) did not affect the basal blood pressure and heart rate, and the responses to aortic nerve stimulation. These findings indicate that NPY, neurotensin and AVP microinjected into the rats NTS can modify the aortic baroreceptor reflex. Some of these neuropeptides may play a role in modulation of the aortic baroreceptor reflex within the NTS.
Similar content being viewed by others
References
Buijs RM (1978) Intra- and extrahypothalamic vasopressin and oxytocin pathways in the rat. Pathways to the limbic system, medulla oblongata and spinal cord. Cell Tiss Res 192:423–435
Carter DA, Vallejo M, Lightman SL (1985) Cardiovascular effects of neuropeptide Y in the nucleus tractus solitarius of rats: relationship with noradrenaline and vasopressin. Peptides 6:421–425
Casto R, Phillips MI (1985) Neuropeptide action in nucleus tractus solitarius: angiotensin specificity and hypertensive rats. Am J Physiol 249: R341-R347
Casto R, Phillips MI (1986) Angiotensin 11 attenuates baroreflexes at nucleus tractus solitarius of rats. Am J Physiol 250:R193-R198
Ciriello J (1983) Brainstem projections of aortic baroreceptor afferent Fibers in the rat. Neurosci Lett 36:37–42
Ciriello J, Calaresu FR (1980) Role of paraventricular and supraoptic nuclei in central cardiovascular regulation in the cat. Am J Physiol 239:R137-R142
De Quidt ME, Emson PC (1986) Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system — II. Immunohistochemical analysis. Neuroscience 18:545–618
Ganten D, Fuxe K, Phillips MI, Mann JFE, Ganten U (1978) The brain isorenin-angiotensin system: biochemistry, localization, and possible role in drinking and blood pressure regulation. In: Ganong WF, Martini L (eds) Frontiers in neuroendocrinology. Raven, New York, vol. 5, pp 61–99
Gehlert DR, Speth RC, Healy DP, Wamsley JK (1984) Autoradiographic localization of angiotensin II receptors in the rat brainstem. Life Sci 34:1565–1571
Gerstberger R, Fahrenholz F (1989) Autoradiographic localization of V1 vasopressin binding sites in rat brain and kidney. Eur J Pharmacol 167:105–116
Gibson TR, Wildey GM, Manaker S, Glembotski CC (1986) Autoradiographic localization and characterization of atrial natriuretic peptide binding sites in the rat central nervous system and adrenal gland. J Neurosci 6:2004–2011
Haeusler G, Osterwalder R (1980) Evidence suggesting a transmitter or neuromodulatory role for substance P at the first synapse of the baroreceptor reflex. Naunyn-Schmiedeber's Arch Pharmacol 314:111–121
Healy DP, Rettig R, Nguyen T, Printz MP (1989) Quantitative autoradiography of angiotensin 11 receptors in the rat solitary-vagal area: effects of nodose ganglionectomy or sinoaortic denervation. Brain Res 484:1–12
Hökfelt T, Everitt BJ, Fuxe K, Kalia M, Agnati L, Johansson O, Härfstrand A, Lundberg JM, Terenius L, TheodorssonNorheim E, Goldstein M (1984) Transmitter and peptide systems in areas involved in the control of blood pressure. Clin Exp Hypertens [A] 6:23–41
Jennes L, Stumpf WE, Kalivas PW (1982) Neurotensin: topographical distribution in rat brain by immunohistochemistry. J Comp Neurol 210:211–224
Kawai Y, Takami K, Shiosaka S, Emson PC, Hillyard CJ, Girgis S, MacIntyre I, Tohyama M (1985) Topographic localization of calcitonin gene-related peptide in the rat brain: an immunohistochemical analysis. Neuroscience 15:747–763
Kawata M, Ueda S, Nakao K, Morii N, Kiso Y, Imura H, Sano Y (1985) Immunohistochemical demonstration of α-atrial natriuretic polypeptide-containing neurons in the rat brain. Histochemistry 83:1–3
King KA, Pang CCY (1987) Cardiovascular effects of injections of vasopressin into the nucleus tractus solitarius in conscious rats. Br J Pharmacol 90:531–536
Kruger L, Mantyh PW, Sternini C, Brecha NC, Mantyh CR (1988) Calcitonin gene-related peptide (CGRP) in the rat central nervous system: patterns of immunoreactivity and receptor binding sites. Brain Res 463:223–244
Kruszynski M, Lammek B, Manning M, Seto J, Haldar J, Sawyer WH (1980) (1-(β-mercapto-β,β-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine) arginine-vasopressin and 1-(β-mercapto-β, β-cyclopentamethylenepropionic acid) argininevasopressin, two highly potent antagonists of the vasopressor response to arginine-vasopressin. J Med Chem 23:364–368
Kubo T, Amano H (1986) Vasopressin-induced pressor responses in rats to bilateral electrolytic lesioning of the caudal portion of the nucleus tractus solitarii. Brain Res 363:183–187
Kubo T, Kihara M (1978a) Blood pressure modulation by substance P in the rat nucleus tractus solitarius. Brain Res 413:379–383
Kubo T, Kihara M (1987b) Evidence for the presence of GABAergic and glycine-like systems responsible for cardiovascular control in the nucleus tractus solitarii of the rat. Neurosci Lett 74:331–336
Kubo T, Kihara M (1988a) Evidence of N-methyl-D-aspartate receptor-mediated modulaton of the aortic baroreceptor reflex in the rat nucleus tractus solitarii. Neurosci Lett 87:69–74
Kubo T, Kihara M (1988b) Evidence for γ-aminobutyric acid receptor-mediated modulation of the aortic baroreceptor reflex in the nucleus tractus solitarii of the rat. Neurosci Lett 89:156–160
Kurihara M, Saavedra JM, Shigematsu K (1987) Localization and characterization of atrial natriuretic peptide binding sites in discrete areas of rat brain and pituitary gland by quantitative autoradiography. Brain Res 408:31–39
Matsuguchi H, Sharabi FM, Gordon FJ, Johnson AK, Schmidt PG (1982) Blood pressure and heart rate responses to microinjection of vasopressin into the nucleus tractus solitarius region of the rat. Neuropharmacology 21:687–693
McKitrick DJ, Calaresu FR (1988) Cardiovascular responses to microinjection of ANF into dorsal medulla of rats. Am J Physiol 255:R182-R187
McKitrick DJ, Calaresu FR (1989) Baroreceptor activation or glutamate coinjection facilitates depressor responses to ANF microinjection into NTS. Am J Physiol 257:R405-R409
Mendelsohn FAO, Quirion R, Saavedra JM, Aguilera G, Catt KJ (1984) Autoradiographic localization of angiotensin 11 receptors in rat brain. Proc Natl Acad Sci USA 81:1575–1579
Michelini LC, Bonagamba GH (1988) Baroreceptor reflex modulation by vasopressin microinjected into the nucleus tractus solitarii of conscious rats. Hypertension (Suppl I):I-75–I-79
Morin-Surun MP, Marlot D, Kessler JP, Denavit-Saubié M (1986) The excitation by neurotensin of nucleus tractus solitarius neurons induces apneustic breathing. Brain Res 384:106–113
Nakajima T, Yashima Y, Nakamura K (1986) Quantitative autoradiographic localization of neuropeptide Y receptors in the rat lower brainstem. Brain Res 380:144–150
Palkovits M (1981) Neuropeptides and biogenic amines in central cardiovascular control mechanisms. In: Buckley JP, Ferario CM (eds) Central nervous system mechanisms in hypertension. Raven, New York, pp 73–87
Palkovits M, Zaborszky L (1977) Neuroanatomy of central cardiovascular control. Nucleus tractus solitarii: afferent and efferent neuronal connections in relation to the baroreceptor reflex arc. Prog Brain Res 47:9–34
Petty MA, De Jong W, De Wied D (1982) An inhibitory role of β-endorphin in central cardiovascular regulation. Life Sci 30:1835–1840
Philippu A (1988) Regulation of blood pressure by central neurotransmitters and neuropeptides. Rev Physiol Biochem Pharmacol 111:1–115
Pittman QJ, Franklin LG (1985) Vasopressin antagonist in nucleus tractus solitarius/vagal area reduces pressor and tachycardia responses to paraventricular nucleus stimulation in rats. Neurosci Lett 56:155–160
Rettig, R, Healy DP, Printz MP (1986) Cardiovascular effects of microinjections of angiotensin 11 into the nucleus tractus solitarii. Brain Res 364:233–240
Saper CB, Standaert DG, Currie MG, Schwartz D, Geller DM, Needleman P (1985) Atriopeptin-immunoreactive neurons in the brain: presence in cardiovascular regulatory areas. Science 5:1047–1049
Sapru HN, Krieger AJ (1977) Carotid and aortic chemoreceptor function in the rat. J Appl Physiol 42:344–348
Sapru HN, Gonzalez E, Krieger AJ (1981) Aortic nerve stimulation in the rat: cardiovascular and respiratory responses. Brain Res bull 6:393–398
Sofroniew MV (1980) Projections from vasopressin, oxytocin, and neurophysin neurons to neural targets in the rat and human. J Histochem Cytochem 28:475–478
Talman WT, Reis DJ (1981) Baroreflex actions of substance P microinjected into the nucleus tractus solitarii in rat: a consequence of local distortion. Brain Res 220:402–407
Tseng C-J, Mosqueda-Garcia R, Appalsamy M, Robertson D (1988) Cardiovascular effects of neuropeptide Y in rat brainstem nuclei. Circulation Res 64:55–61
Uhl GR, Goodman RR, Snyder SH (1979) Neurotensin-containing cell bodies, fibers and nerve terminals in the brain stem of the rat: immunohistochemical mapping. Brain Res 167:77–91
Vallejo M, Carter DA, Lightman SL (1984) Haemodynamic effects of arginine-vasopressin microinjections into the nucleus tractus solitarius: a comparative study of vasopressin, a selective vasopressin receptor agonist and antagonist, and oxytocin. Neurosci Lett 52:247–252
Vallejo M, Lightman S, Marshall I (1988) Central cardiovascular effects of calcitonin gene-related peptide: interaction with noradrenaline in the nucleus tractus solitarius of rats. Exp Brain Res 70:221–224
Yamazoe M, Shiosaka S, Emson PC, Tohyama M (1985) Distribution of neuropeptide Y in the lower brainstem: an immunohistochemical analysis. Brain Res 335:109–120
Young WS III, Kuhar MJ (1981) Neurotensin receptor localization by light microscopic autoradiogaphy in rat brain. Brain Res 206:273–285
Author information
Authors and Affiliations
Additional information
Send offprint requests to T. Kubo at the above address
Rights and permissions
About this article
Cite this article
Kubo, T., Kihara, M. Modulation of the aortic baroreceptor reflex by neuropeptide Y, neurotensin and vasopressin microinjected into the nucleus tractus solitarii of the rat. Naunyn-Schmiedeberg's Arch Pharmacol 342, 182–188 (1990). https://doi.org/10.1007/BF00166962
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00166962