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Cardiovascular regulatory actions of the hypocretins in brain
W K Samson1, B Gosnell, J K Chang
1Department of Physiology, University of North Dakota School of Medicine, 501 North Columbia Road, Grand Forks, ND 58202-9037, USA. wsamson@mail.med.und.nodak.edu
Abstract:
The hypocretins, also known as the orexins, are alternate translation products of a single gene. The recognition of their production in neurons of the rostral diencephalon, and their axonal localization in brain sites known to be important in the control of appetite, led to the demonstration of their orexogenic actions. However, these peptides are not as potent as other appetite stimulating neuropeptides and they have been localized in areas of brain more related to cardiovascular function. We verified the orexogenic actions of hypocretin-1 (Hcrt-1) and hypocretin-2 (Hcrt-2) in an ad libitum feeding model and identified the threshold dose to be 1 nmol when given into the lateral cerebroventricle (i.c. v.). Even at threshold doses for feeding, both Hcrt-1 and Hcrt-2 given i.c.v. into conscious, unrestrained rats stimulated significant elevations in mean arterial blood pressure, that appeared dose related. These elevations were relatively long lasting, mirroring the time course of a pressor dose of angiotensin II (0.1 nmol i.c.v.); however, the magnitude of blood pressure elevation to hypocretin did not equal that of A II. These data suggest an additional, non-appetitive action of the hypocretins and indicate that the peptide and receptor mapping studies may have predicted important roles for the peptides in the central nervous system control of cardiovascular function.
Insights
Hypocretins (orexins) stimulate feeding and also increase blood pressure in rats. These findings suggest hypocretins have dual roles in appetite and cardiovascular regulation.
Area of Science:
- Neuroscience
- Endocrinology
- Cardiovascular Physiology
Background:
- Hypocretins (orexins) are neuropeptides produced in the brain.
- Their localization suggests roles in appetite and cardiovascular control.
- Previous studies indicated orexigenic actions, but potency and other functions were unclear.
Purpose of the Study:
- To verify the orexigenic effects of hypocretin-1 and hypocretin-2.
- To investigate the cardiovascular effects of these peptides.
- To determine the dose-response relationship for feeding and blood pressure changes.
Main Methods:
- Administered hypocretin-1 and hypocretin-2 intracerebroventricularly (i.c.v.) in a rat feeding model.
- Monitored mean arterial blood pressure in conscious, unrestrained rats.
- Compared hypocretin effects to angiotensin II.
Main Results:
- Identified a threshold dose of 1 nmol for hypocretin-induced feeding.
- Both hypocretins significantly elevated blood pressure at feeding threshold doses.
- Blood pressure elevations were dose-related and long-lasting, though less potent than angiotensin II.
Conclusions:
- Hypocretins possess significant non-appetitive cardiovascular effects.
- These peptides play a dual role in regulating both feeding and blood pressure.
- Central nervous system control of cardiovascular function may involve hypocretins.