We investigated the involvement of the nitric oxide pathway in the inhibitory mechanisms of 5-hydroxytryptamine (5-HT) in the pressor responses induced by stimulation of sympathetic vasopressor outflow in diabetic pithed rats.
Diabetes was induced in male Wistar rats by a single s.c. injection of alloxan. Four weeks later, the animals were anaesthetized, pretreated with atropine, and pithed. Electrical stimulation of the sympathetic outflow from the spinal cord (0.1, 0.5, 1 and 5 Hz) resulted in frequency-dependent increases in blood pressure.
The inhibition of electrically induced pressor responses by 5-HT (10 μg/kg/min) in diabetic pithed rats could not be elicited after i.v. treatment with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 μg/kg), a guanylyl cyclase inhibitor, or N-ω-l-Arginine methyl ester hydrochloride (l-NAME) (10 mg/kg), a nitric oxide synthase (NOS) inhibitor.
The inhibitory effect produced by infusion of the selective 5-HT1A receptor agonist 8-hydroxydipropylaminotretalin hydrobromide (8-OH-DPAT) (20 μg/kg/min) was abolished in the presence of ODQ (10 μg/kg), or l-NAME (10 mg/kg) in diabetic pithed rats.
The administration of l-Arginine (100 mg/kg) 30 min after l-NAME reproduced the inhibitory effect caused by 5-HT (10 μg/kg/min) and 8-OH-DPAT (20 μg/kg/min) on the electrically induced pressor responses, whereas in the presence of d-Arginine (100 mg/kg) + l-NAME the 5-HT or 8-OH-DPAT inhibitory effect on the pressor responses was abolished.
In conclusion, in diabetic pithed rats, the inhibition produced by prejunctional 5-HT1A activation on electrically induced sympathetic pressor responses is mediated by the NO synthesis/pathway.