Endothelin has previously been localised in perivascular nerves of the rat basilar artery. Considering its potent vasoconstrictor and mitogenic properties on vascular smooth muscle, the potential role of a neural source of this peptide in hypertension has been investigated. The trigeminal, superior cervical and sphenopalatine ganglia of Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 16 weeks of age have been examined for immunolocalisation of endothelin at the light and electron microscope level. At the light microscope level, neurones immunopositive for endothelin were detected in these ganglia of the SHR but were not seen in ganglia from WKY rats. This difference was particularly marked in the trigeminal ganglia where endothelin-positive neurones colocalised with substance P immunoreactivity. Using in situ hybridisation techniques, endothelin-1 mRNA was localised to the cytoplasm of neurones in the ganglia and was more prominent in the SHR. At the electron microscope level, endothelin-immunoreactivity was localised at the peripheral perikarya of some neuronal cell bodies of the trigeminal, superior cervical and sphenopalatine ganglia of WKY rats but was more prominent with heavy labelling throughout the cytoplasm of neurones in the SHR. Notably, in the trigeminal ganglia of the SHR only, some endothelin-immunopositive nerve fibres appeared to be damaged and contained vacuoles with granular material. Ultrastructural examination of the basilar artery revealed an increased number of endothelin-positive axons in the SHR, but these axons usually showed selective damage. In summary, in the SHR, there was a marked increase in endothelin particularly in sensory neurones projecting to the basilar artery which also appear to be undergoing degenerative changes. An increased neural source of endothelin in the SHR may contribute to the development of hypertension or may be a consequence of selective degenerative change.

Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mistui Y, Yasaki Y, Goto K, Nasaki T: A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988;332:411–415.
Tasaka K, Kitazumi K: The control of endothelin-1 secretion. Gen Pharmacol 1994;25:1059–1069.
Sharifi AM, Schiffrin EL: Apoptosis in aorta of deoxycorticosterone acetate-salt hypertensive rats: Effect of endothelin receptor antagonism. J Hypertens 1997;15:1441–1448.
Nava E, Luscher TF: Endothelium-derived vasoactive factors in hypertension: Nitric oxide and endothelin. J Hypertens 1995;13(suppl):S39–S48.
Rosendorff C: Endothelin, vascular hypertrophy, and hypertension. Cardiovasc Drugs Ther 1997;10:795–802.
Suzuki N, Miyauch T, Tomobe Y, Matsumoto H, Goto K, Masaki T, Fujino M: Plasma concentration of endothelin-1 in spontaneously hypertensive rats and DOCA-salt hypertensive rats. Biochem Biophys Res Commun 1990;167:941–947.
Rubanyi GM, Polokoff MA: Endothelins: Molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev 1994;46:325–415.
Schiffrin EL: Endothelin: Potential role in hypertension and vascular hypertrophy. Hypertension 1995;25:1135–1143.
Loesch A, Milner P, Burnstock G: Endothelin in perivascular nerves. An electron-immunocytochemical study of rat basilar artery. Neuroreport 1998;9:3903–3906.
Giaid A, Gibson SJ, Ibrahim NBN, Legon S, Bloom SR, Yanagisawa M, Masaki T, Varndell IM, Polak JM: Endothelin 1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia. Proc Natl Acad Sci USA 1989;86:7634–7638.
Inagaki H, Bishop AE, Yura J, Polak JM: Localization of endothelin-1 and its binding sites to the nervous system of the human colon. J Cardiovasc Pharmacol 1991;17(suppl 7):S455–S457.
Matsuyama T, Shiosaka S, Wanaka A, Yoneda S, Kimura K, Hayakawa T, Emson PC, Tohyama M: Fine structure of peptidergic and catecholaminergic nerve fibres in the anterior cerebral artery and their interrelationships: An immunoelectron microscopic study. J Comp Neurol 1985;235:268–276.
Suzuki N, Hardebo JE, Owman C: Origins and pathways of cerebrovascular nerves storing substance P and calcitonin gene-related peptide in rat. Neuroscience 1989;31:427–438.
Mione MC, Cavanagh JFR, Lincoln J, Milner P, Burnstock G: Long-term chemical sympathectomy leads to an increase of neuropeptide Y immunoreactivity in cerebrovascular nerves and iris of the developing rat. Neuroscience 1990;34:369–378.
Nozaki K, Moskowitz MA, Maynard KI, Koketsu N, Dawson TM, Bredt DS, Snyder SH; Possible origins and distribution of immunoreactive nitric oxide synthase-containing nerve fibres in cerebral arteries. J Cereb Blood Flow Metab 1993;13:70–79.
Edvinsson L, Jansen-Olesen I, Gulbenkian S, Uddman R: Vascular afferent nerves: Involved in local blood flow regulation?; in The Autonomic Nervous System. Burnstock G: Nervous Control of Blood Vessels; Bennett T, Gardiner SM (sect eds). Chur, Harwood Academic Publishers, 1996, pp 113–134.
Peters A, Palay SL, Webster HdeF (eds): The Fine Structure of the Nervous System. Neurons and Their Supporting Cells, ed 3. Oxford, Oxford University Press, 1991.
Dhital KK, Gerli R, Lincoln J, Milner P, Tanganelli P, Weber G, Fruschelli C, Burnstock G: Increased density of perivascular nerves to the major cerebral vessels of the spontaneously hypertensive rat: Differential changes in noradrenaline and neuropeptide Y during development. Brain Res 1988;444:33–45.
Lee RMKW, Borkowski KR, Leenen FHH, Tsoporis J, Coughlin M: Combined effect of neonatal sympathectomy and adrenal demedullation on blood pressure and vascular changes in spontaneously hypertensive rats. Circ Res 1991;69:714–721.
Brock JA, Van Helden DK, Dosen P, Rush RA: Prevention of high blood pressure by reducing sympathetic innervation in the spontaneously hypertensive rat. J Auton Nerv Syst 1996;61:97–102.
Kawasaki H, Saito A, Takasaki K: Age-related decrease of calcitonin gene-related peptide-containing vasodilator innervation in the mesenteric resistance vessel of the spontaneously hypertensive rat. Circ Res 1990;67:733–743.
Mosqueda-Garcia R, Stainback R, Fernandez-Violante R, Hamakubo T: Cardiovascular effects of endothelin injected into brain nuclei regulating vasopressin release. J Cardiovasc Pharmacol 1995;26(suppl 3):S159–S162.
Zhu B, Herbert J: Behavioural, autonomic and endocrine responses associated with C-fos expression in the forebrain and brainstem after intracerebroventricular infusions of endothelins. Neuroscience 1996;71:1049–1062.
Szolcsányi J, Oroszi G, Németh J, Szilvássy Z, Tósaki A: Endothelin release by capsaicin in isolated working rat heart. Eur J Pharmacol 1999;376:247–250.
Belai A, Lincoln J, Burnstock G: Lack of release of vasoactive intestinal polypeptide and calcitonin gene-related peptide during electrical stimulation of enteric nerves in streptozotocin-diabetic rats. Gastroenterology 1987;93:1034–1040.
Belai A, Lincoln J, Milner P, Burnstock G: Progressive changes in adrenergic, serotonergic, and peptidergic nerves in proximal colon of streptozotocin-diabetic rats. Gastroenterology 1988;95:1234–1241.
Loesch A, Belai A, Lincoln J, Burnstock G: Enteric nerves in diabetic rats: Electron microscopic evidence for neuropathy of vasoactive intestinal polypeptide-containing fibres. Acta Neuropathol 1986;70:161–168.
Lu MH, Wu GC, Chao CF: Comparison of endothelin binding sites in cultured aortic smooth muscle cells from spontaneously hypertensive and normotensive rats. Jpn Circ J 1997;61:145–150.
Wong-Dusting HK, La M, Rand MJ: Mechanisms of the effects of endothelin on responses to noradrenaline and sympathetic nerve stimulation. Clin Exp Pharmacol Physiol 1990;17:269–273.
Dymshitz J, Vasko MR: Endothelin-1 enhances capsaicin-induced peptide release and cGMP accumulation in cultures of rat sensory neurons. Neurosci Lett 1994;167:128–132.
Trippodo NC, Frohlich ED: Similarities of genetic (spontaneous) hypertension: Man and rat. Circ Res 1981;48:309–319.
Schiffrin EL: Endothelin: Role in hypertension; in Born GVR, Schwartz CJ (eds): Vascular Endothelium: Physiology, Pathology and Therapeutic Opportunities. Stuttgart, Schattauer, 1997, pp 355–372.
Schiffrin EL, Turgeon A, Deng LY: Effect of chronic ETA-selective endothelin antagonism on blood pressure in experimental and genetic hypertension in rats. Br J Pharmacol 1997;121:935–940.
Deng LY, Schiffrin EL: Endothelin-1 gene expression in blood vessels and kidney of spontaneously hypertensive rats (SHR), L-NAME-treated SHR, and renovascular hypertensive rats. J Cardiovasc Pharmacol 1998;31(suppl 1):S380–S383.
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