Cardiovascular Actions of Orexin‐A in the Rat Subfornical Organ

Orexin‐A is a neuropeptide, primarily produced in the lateral hypothalamic/perifornical hypothalamus. Orexin receptors and immunoreactive neuronal fibres are widely distributed throughout the brain, suggesting integrative neurotransmitter roles in a variety of physiological systems. Intracerebroventricular injections of orexin‐A increase blood pressure and stimulate drinking, and the subfornical organ (SFO), a circumventricular structure implicated in autonomic control, is a potential site at which orexin may act to exert these effects. We have therefore used microinjection techniques to examine the effects of orexin‐A administered directly into the SFO on blood pressure and heart rate in urethane anaesthetised male Sprague‐Dawley rats. Orexin‐A microinjection (50 fmol) into the SFO caused site‐specific decreases in blood pressure (SFO: mean area under curve (AUC) = −681.7 ± 46.8 mmHg*s, n = 22 versus non‐SFO: 63.68 ± 54.69 mmHg*s, n = 15, P < 0.001), and heart rate (SFO: mean AUC = −26.7 ± 2.8 beats, n = 22, versus non‐SFO: mean AUC = 1.62 ± 2.1 beats, n = 15, P < 0.001). Vagotomy did not alter the hypotensive or bradycardic responses elicited by orexin‐A microinjection. Prior α‐adrenoceptor blockade with phenoxybenzamine (1 mg/kg, i.v.) masked the orexin‐A induced blood pressure (mean AUC = −122.6 ± 17.6 mmHg*s, n = 4, P < 0.01 paired t‐test) and heart rate (mean AUC = −6.7 ± 1.7 beats, n = 4, P < 0.05, paired test) response. The orexin‐A induced heart rate response was attenuated when β‐adrenoceptors were blocked with propranolol (1 mg/kg, i.v.; mean AUC = 0.6 ± 2.8 beats, n = 5, P < 0.01 paired t‐test). These studies demonstrate that microinjection of orexin‐A into the SFO causes site specific decreases in blood pressure and heart rate which is mediated by a reduction in sympathetic tone.