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Effects of central hypocretin-1 administration on hemodynamic responses in young-adult and middle-aged rats
- Source :
- Brain research. 981(1-2)
- Publication Year :
- 2003
-
Abstract
- The prevalence of hypertension in middle age correlates with impaired autonomic regulation and as norepinephrinergic neurons decline with increasing age, and this reduction may contribute to this impairment. Central hypocretin-activated norepinephrinergic neurons contribute to sympathetic regulation. In the present study we compared sympathoadrenal effects of intracerebroventricular (i.c.v.) hypocretin-1(5 nmol) between young-adult (12–14 weeks) and middle-aged (12–14 months) rats. Arterial blood pressure, heart rate and plasma catecholamines were assessed under pentobarbital anesthesia. In addition, we compared hypocretin-1 and K+-evoked norepinephrine release from the cerebrocortical slices prepared from young-adult and middle-aged rats. We also examined whether the novel hypocretin receptor-1 antagonist (SB-334867) could reverse these hypocretin-1 effects both in vivo and in vitro. I.c.v. hypocretin-1 significantly increased blood pressure by some 7%, heart rate by 9% and plasma norepinephrine concentrations by 100% in young-adult rats. In middle-aged rats these parameters did not change. Plasma epinephrine did not increase in either group. There was a significant correlation between changes in mean arterial pressure and plasma norepinephrine. Similarly, hypocretin-1 evoked norepinephrine release from cerebrocortical slices prepared from young-adult rats was significantly higher than that of middle-aged rats whilst K+-evoked release did not differ between the groups. SB-334867 significantly attenuated hypocretin-1-increased blood pressure and both in vivo and in vitro norepinephrine release. The present data suggest that hypocretinergic neurons may contribute to the regulation of central but not adrenal sympathetic activity. Moreover, sympathetic regulation by hypocretinergic neurones may disappear in middle-age in rats.
- Subjects :
- Male
Mean arterial pressure
medicine.medical_specialty
Aging
Time Factors
Hemodynamics
Blood Pressure
In Vitro Techniques
Potassium Chloride
Norepinephrine (medication)
Hemoglobins
Norepinephrine
Heart Rate
Internal medicine
Heart rate
medicine
Animals
Urea
Naphthyridines
Molecular Biology
Chromatography, High Pressure Liquid
Injections, Intraventricular
Cerebral Cortex
Benzoxazoles
Orexins
business.industry
General Neuroscience
Neuropeptides
Intracellular Signaling Peptides and Proteins
Orexin
Rats
Autonomic nervous system
Disease Models, Animal
Blood pressure
Endocrinology
nervous system
Catecholamine
Neurology (clinical)
Blood Gas Analysis
business
Carrier Proteins
Developmental Biology
medicine.drug
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 981
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- Brain research
- Accession number :
- edsair.doi.dedup.....d5c8a98aa2a87002f04dabbcc5820fc3