The nitric oxide synthesis/pathway mediates the inhibitory serotoninergic responses of the pressor effect elicited by sympathetic stimulation in diabetic pithed rats

    loading  Checking for direct PDF access through Ovid

Abstract

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.

Related Topics

    loading  Loading Related Articles