Neural endothelin in hypertension: increased expression in ganglia and nerves to cerebral arteries of the spontaneously hypertensive rat.
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.
Milner
P
P
Autonomic Neuroscience Institute, Royal Free and University College Medical School, London, UK. p.milner@ucl.ac.uk
Loesch
A
A
Burnstock
G
G
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001488:Basilar Artery / Q000378:metabolism / Q000648:ultrastructure; D001794:Blood Pressure; D002536:Cerebral Arteries / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D005726:Ganglia, Parasympathetic / Q000378:metabolism; D005786:Gene Expression Regulation; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000378:metabolism / Q000648:ultrastructure; D009420:Nervous System / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017783:Superior Cervical Ganglion / Q000378:metabolism; D013599:Systole; D012668:Trigeminal Ganglion / Q000378:metabolism
D019332:Endothelin-1; D016232:Endothelins; D012333:RNA, Messenger