Neuronostatin acts in Brain to Biphasically Increase Mean Arterial Pressure Through Sympatho-activation Followed by Vasopressin Secretion: The Role of Melanocortin Receptors

Author

Gina L.C. Yosten, Missouri University of Science and TechnologyFollow
Alicia T. Pate
Willis K. Samson

Abstract

Neuronostatin is a recently described neuropeptide that is derived from the somatostatin preprohormone. We have shown previously that neuronostatin led to a biphasic, dose-related increase in mean arterial pressure when injected into the lateral cerebroventricle of adult, male rats. Because neuronostatin depolarized both magnocellular and parvocellular, paraventricular nucleus neurons in hypothalamic slice preparations, we hypothesized that neuronostatin elevated mean arterial pressure first by stimulating sympathetic nervous system activity followed by the release of a pressor hormone, specifically vasopressin. We found that the first phase of neuronostatin-induced increase in mean arterial pressure was reversed by pretreatment with phentolamine, indicating that phase 1 was, indeed, due to an increase in sympathetic activity. We also found that centrally injected neuronostatin led to a dose-related increase in vasopressin secretion in a time course consistent with the peak of the second phase. Furthermore, the second phase of arterial pressure elevation was reversed by pretreatment with a vasopressin 1 receptor antagonist, indicating that phase 2 was likely due to an increase in vasopressin secretion. We previously have shown that the anorexigenic and antidipsogenic effects of neuronostatin were reversed by pretreatment with the melanocortin 3/4 receptor antagonist, SHU9119, so we evaluated the ability of SHU9119 to reverse the effects of neuronostatin on MAP and vasopressin secretion. We found that SHU9119 abrogated the second phase of neuronostatin-induced increase in MAP and neuronostatin-induced vasopressin secretion, indicating that neuronostatin acts through the central melanocortin system to increase vasopressin release, ultimately leading to an elevation in MAP. © 2011 the American Physiological Society.

Recommended Citation

G. L. Yosten et al., "Neuronostatin acts in Brain to Biphasically Increase Mean Arterial Pressure Through Sympatho-activation Followed by Vasopressin Secretion: The Role of Melanocortin Receptors," American Journal of Physiology Regulatory Integrative and Comparative Physiology, vol. 300, no. 5, pp. R1194 - R1199, American Physiological Society, May 2011.

The definitive version is available at https://doi.org/10.1152/ajpregu.00849.2010

Department(s)

Biological Sciences

Publication Status

Open Access

Comments

National Institute of General Medical Sciences, Grant T32GM008306

Keywords and Phrases

Blood pressure; Melanocortins; Vasopressin

International Standard Serial Number (ISSN)

1522-1490; 0363-6119

Document Type

Article - Journal

Document Version

Final Version

File Type

text

Language(s)

English

Rights

© 2025 American Physiological Society, All rights reserved.

Creative Commons Licensing

This work is licensed under a Creative Commons Attribution 4.0 License.

Publication Date

01 May 2011

PubMed ID

21325646