Systems NeuroscienceResearch PaperFunctional and in situ hybridization evidence that preganglionic sympathetic vasoconstrictor neurons express ghrelin receptors
Section snippets
Physiological studies
A total of 98 male Sprague–Dawley rats with an average weight of 350 g and average age of 60 days were supplied with food and water ad libitum prior to experiments. The procedures were approved by the University of Melbourne Animal Experimentation Ethics Committee and the Animal Care Committee of the School of Veterinary Sciences, Gifu University. Rats were sedated with ketamine hydrochloride (50–60 mg/kg i.m.) and anesthesia was induced with α-chloralose (60 mg/kg i.v.). Following
Effects of intravenous administration of ghrelin receptor agonists
I.v. administration of either ghrelin receptor agonist, at doses ranging from 2.5–10 mg/kg (CP464709) and 0.5–1.5 mg/kg (GSK894490), gave a characteristic blood pressure response, consisting of a rapid initial blood pressure decrease, followed by a longer lasting rise in blood pressure (Fig. 1). The decrease was dose-dependent, with a larger fall with increasing agonist concentration (Table 1), whereas the blood pressure increases to each drug were similar at doses in the range tested. The
Discussion
The present study provides evidence that autonomic preganglionic neurons in the spinal cord express the ghrelin receptor and that ghrelin receptor agonists can activate some of these neurons to increase blood pressure. By contrast, activation of peripheral ghrelin receptors caused blood pressure to decrease, probably by a direct action on blood vessels.
Conclusion
We conclude that ghrelin receptors are expressed by sympathetic preganglionic neurons of vasoconstrictor pathways and that their activation increases blood pressure. Thus it may be feasible to target ghrelin receptors to control blood pressure.
Acknowledgments
This work was supported by a grant from the National Health and Medical Research Council of Australia (Grant number 508947). We thank Zhengdong Qu for assistance with in situ hybridization. Microscope facilities were provided by the Australian Phenomics Network Histopathology and Organ Pathology Node.
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