Neural Endothelin in Hypertension: Increased Expression in Ganglia and Nerves to Cerebral Arteries of the Spontaneously Hypertensive Rat

Abstract

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.

Increased O 2 ·− Production and Upregulation of ET B Receptors by Sympathetic Neurons in DOCA-Salt Hypertensive Rats

“…In contrast, in the superior cervical ganglia of spontaneously hypertensive rats, there is an increased intracellular ET-1 immunoreactivity and mRNA. 25 This may reflect different ganglia and/or different hypertensive models. ET-1 can be released from the cultured sympathetic neurons 7 analogous to endothelial cells.…”

Endothelin-1 and endothelin receptors in the basilar artery of the capybara

“…ET-1 has previously been demonstrated in the cerebral vascular bed of mammals including rat, rabbit and man, where it was mainly localised to cerebrovascular endothelial cells (Loesch et al 1993, Gorelova et al 1996, Loesch & Burnstock 1996a, b, 1998, Shochina et al 1997. ET-1 has also been shown in cerebrovascular autonomic nerves to large cerebral arteries of rat and man , Milner et al 2000a, Loesch & Burnstock 2002, Loesch 2003. Studies on sensory and sympathetic denervation of the rat suggested that sensory autonomic nerves projecting from the trigeminal ganglion are a more likely source of ET-1-containing perivascular nerves in cerebral arteries than sympathetic nerves from the superior cervical ganglion (Milner et al 2000b).…”

Structure and Function of Smooth Muscle with Special Reference to Mast Cells

“…ET was reported to be present in the basilar artery of the rat [58,59] and post mortem, in human cerebrovascular nerves of the middle cerebral artery [60]. Immunoreactive ET-1 was also detected in endothelial cells of the intima, vascular smooth muscle cells and macrophages of the media and neointima, and in perivascular nerves (axons) varicosities at the boundary between media and adventitia of the middle cerebral artery in a patient with multiple system atrophy with autonomic deficiency [61].…”