Antagonism of orexin receptors significantly lowers blood pressure and exaggerated CO2 chemoreflex in spontaneously hypertensive rats (872.2)

Abstract

The orexin system is involved in cardiorespiratory function as well as wake‐sleep regulation. We recently showed that in spontaneously hypertensive rats (SHRs): 1) blocking both orexin receptors by oral administration of an antagonist, almorexant (almxt), significantly lowers blood pressure in wakefulness and NREM sleep in both dark and light periods of the diurnal cycle, 2) the anti‐hypertension effect is accompanied by decreased sympathetic vasomotor tone and noradrenaline levels in cerebrospinal fluid and plasma, 3) there is a strong trend towards increased orexin‐A mRNA expression in the rostral ventrolateral medulla, a projection site for orexinergic lateral hypothalamic (LHA) neurons, 4) there is an exaggerated CO2 ventilatory chemoreflex, which can be normalized by blocking orexin receptors with almxt. Antagonism of orexin receptors had no effect on resting blood pressure in normotensive WKY rats. We interpret these results to suggest that an overactive orexin system may play a significant role in the development and maintenance of high blood pressure and enhanced CO2 chemoreflex in SHRs. Modulation of orexin and the hypothesized overactive central chemoreflex could be a potential target in treating hypertension.Grant Funding Source: NIH HL 28066