An augmented CO2 chemoreflex and overactive orexin system are linked with hypertension in young and adult spontaneously hypertensive rats (SHRs)

Abstract

Activation of central chemoreceptors by CO₂ increases arterial blood pressure (ABP), sympathetic nerve activity (SNA), and breathing. In spontaneously hypertensive rats (SHRs), high ABP is associated with enhanced SNA and peripheral chemoreflexes. We hypothesized that an augmented CO₂ chemoreflex and overactive orexin system are linked with high ABP in both young (P30-58 days) and adult (4–6 months) SHRs. We show: 1) An augmented CO₂ chemoreflex and higher ABP in SHRs are measureable at a young age and increase in adulthood. In wakefulness, the ventilatory response to normoxic-hypercapnia is higher in young SHRs (179 ± 11 SEM % increase) than in age-matched normotensive Wistar-Kyoto (WKY) rats (114 ± 9% increase), but lower than in adult SHRs (226 ± 10% increase) (P < 0.05). The resting ABP is higher in young SHRs (122 ± 5 mmHg) than in age-matched WKY rats (99 ± 5 mmHg), but lower than in adult SHRs (152 ± 4 mmHg) (P < 0.05). 2) SHRs have more orexin neurons and more CO₂-activated orexin neurons in the hypothalamus. 3) Antagonism of orexin receptors with a dual orexin receptor antagonist, almorexant, normalizes the augmented CO₂ chemoreflex in young and adult SHRs and the high ABP in young SHRs, and significantly lowers ABP in adult SHRs. 4) Attenuation of peripheral chemoreflexes by hyperoxia does not abolish the augmented CO₂ chemoreflex (breathing and ABP) in SHRs, which indicates an important role for the central chemoreflex. We suggest that an overactive orexin system may play an important role in the augmented central CO₂ chemoreflex and in the development of hypertension in SHRs.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://ift.tt/1Q03qcf
via IFTTT