Elsevier

Neuroscience

Volume 155, Issue 1, 31 July 2008, Pages 241-249
Neuroscience

Neuropharmacology
Effect of central urotensin II on heart rate, blood pressure and brain Fos immunoreactivity in conscious rats

https://doi.org/10.1016/j.neuroscience.2008.05.032Get rights and content

Abstract

Central administration of urotensin II (UII) increases heart rate (HR), cardiac contractility, and plasma levels of epinephrine and glucose. To investigate the mechanisms causing these responses we examined the effects of i.c.v. administration of rat UII (10 μg) on the sympatho-adrenal and pituitary–adrenal axes in conscious rats, and we mapped the brain sites activated by UII by immunohistochemically detecting Fos expression. In six conscious rats i.c.v. UII, but not vehicle, increased HR significantly 60–90 min after treatment and increased plasma glucose at 60 and 90 min, both indicators of increased epinephrine release. Plasma corticosterone levels were significantly elevated 90 min after i.c.v. UII. Conscious rats, given i.c.v. UII (n=12) and killed after 100 or 160 min, showed increased Fos-immunoreactivity (Fos-IR) in the nucleus of the solitary tract and the central nucleus of the amygdala (CeA) at both time points, compared with vehicle (n=11). In UII-treated rats, Fos-IR in the paraventricular nucleus of the hypothalamus (PVN) was significantly elevated at 160 min, but not 100 min, compared with vehicle. There were no increases in Fos-IR in the rostral ventrolateral medulla or the A5 cell group, areas associated with sympathetic outflow to the adrenal gland. In summary, i.c.v. UII increased HR and plasma glucose and corticosterone in conscious rats. UII increased Fos-IR in the CeA and PVN, but over a longer time course in the latter. These findings indicate that UII acts on specific brain nuclei to stimulate the hypothalamo-pituitary–adrenal axis and to stimulate adrenal sympathetic nerve activity.

Section snippets

Experimental procedures

Twenty-three male Sprague–Dawley rats weighing 282±8 g were kept in temperature- (22 °C) and light-controlled conditions (12-h light/dark), with ad libitum access to standard rat chow and water. All rats were weighed daily. All experimental procedures were approved by the Animal Experimentation Ethics Committee of the Howard Florey Institute under guidelines laid down by the National Health and Medical Research Council of Australia in line with the international guidelines on the ethical use of

HR and SBP

There was no significant change in sBP measured either 0–30 min or 60–90 min after i.c.v. administration of UII (Fig. 1a). At 0–30 min after i.c.v. treatment HR did not differ significantly between UII and aCSF treatments (Fig. 1b), but by 60–90 min following i.c.v. UII there was a large increase in HR compared with the same time period after aCSF (P=0.003) (Fig. 1b).

Plasma corticosterone and plasma glucose

Plasma corticosterone levels were significantly higher at 90 min after i.c.v. UII compared with after i.c.v. aCSF (614±72 and

Discussion

In this study we demonstrated that i.c.v. administration of UII to conscious rats causes similar responses to those that we have seen in conscious sheep (Watson et al., 2003), including increased secretion of corticosteroids, tachycardia and hyperglycemia. In addition, we observed activation of several brain nuclei involved in corticosteroid release. Together with our previous studies, these findings suggest that UII acts on specific brain nuclei to stimulate the hypothalamo-pituitary–adrenal

Conclusion

In conclusion, this study has shown that i.c.v. UII increases plasma corticosterone and glucose levels as well as HR in conscious rats. Significantly greater Fos-IR was seen initially in the CeA then later in the PVN, suggesting that the amygdala plays an important role in mediating the actions of i.c.v. UII. No staining was seen in the A5 area or caudal raphe nuclei, suggesting that these areas are not associated with the UII-mediated epinephrine release via an increase in sympathetic outflow

Acknowledgments

The authors are grateful to Dr. B. J. Oldfield for assistance with image analysis and to Craig Thomson for his excellent technical assistance. Preliminary results of this work have been published in abstract form (Watson and May, 2004a).

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    Present address: Baker Heart Research Institute, PO Box 6492, St. Kilda Road Central, Melbourne, Victoria 3010, Australia.

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