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The Cyclooxygenase and Nitric Oxide synthesis/pathways Mediate the Inhibitory Serotonergic Response to the Pressor Effect Elicited by Sympathetic Stimulation in Long-Term Diabetic Pithed Rats

The Cyclooxygenase and Nitric Oxide synthesis/pathways Mediate the Inhibitory Serotonergic Response to the Pressor Effect Elicited by Sympathetic Stimulation in Long-Term Diabetic Pithed Rats

B Restrepo, M García, C López, M L Martín, L San Román, A Morán

Pharmacology. 2012;90(3-4):169-76.

PMID: 22948792

Abstract:

We investigated the mechanisms involved in the 5-hydroxytriptaminergic inhibitory action on the pressor responses elicited by sympathostimulation in long-term-diabetic pithed rats. Diabetes was induced in rats by alloxan administration. Eight weeks later, the animals were anaesthetized and pithed. The action and mechanisms of 5-HT were analysed based on the pressor responses induced by sympathostimulation. In 8-week-diabetic animals, 5-HT (20 µg/kg/min) inhibits the pressor effect of sympathostimulation which is reproduced by two selective 5-HT(1A) and 5-HT(2) receptor agonists: 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT, 5 µg/kg/min) and α-methyl-5-HT (5 µg/kg/min). A bolus injection of 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ, 10 µg/kg), or L-arginine HCl, N(ω)-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg), an inhibitor of NO production, prior to the infusion of 8-OH-DPAT (5 µg/kg/min) reversed the inhibitory effect of 8-OH-DPAT. The inhibitory effect of infusion of α-methyl 5-HT (5 µg/kg/min) was abolished in the presence of indomethacin (2 mg/kg), a non-selective cyclooxygenase (COX) inhibitor, or FR 122047 (1.5 mg/kg) or nimesulide (1.5 mg/kg), two selective COX-1 and COX-2 inhibitors, respectively, in long-term-diabetic pithed rats. Our results indicate that 5-HT inhibition of the pressor responses induced by electrical stimulation is mediated both by the NO and COX pathways in long-term-diabetic rats.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4243272	FR 122047 hydrochloride			Price

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