Diabetes-induced Changes in the 5-hydroxytryptamine Inhibitory Receptors Involved in the Pressor Effect Elicited by Sympathetic Stimulation in the Pithed Rat

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2005 Apr 27

PMID 15852039

Citations 3

Authors

Monica Garcia

Asuncion Moran

Elena Calama

Maria Luisa Martin

Mariette Barthelmebs

Luis San Roman

Affiliations

Soon will be listed here.

Abstract

1. We investigated the effect of alloxan-induced diabetes on the inhibitory mechanisms of 5-hydroxytryptamine (5-HT) in the pressor responses induced by stimulation of sympathetic vasopressor outflow in pithed rats, and analysed the type and/or subtype of 5-HT receptors involved. 2. Diabetes was induced in male Wistar rats by a single s.c. injection of alloxan, then 4 weeks later, they 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. 3. Intravenous infusions of 5-HT (1-80 microg kg(-1) min(-1)) reduced the pressor effects obtained by electrical stimulation. The 5-HT(1) receptor agonist 5-carboxamidotryptamine, 5-CT (5 microg kg(-1) min(-1)), caused an inhibition of the pressor response, whereas the selective 5-HT(2) receptor agonist, alpha-methyl-5-HT (5 microg kg(-1) min(-1)) and the selective 5-HT(3) receptor agonist, 1-phenylbiguanide (40 microg kg(-1) min(-1)), did not modify the sympathetic pressor responses. 5-HT had no effect on exogenous noradrenaline (NA)-induced pressor responses. 4. The inhibition of electrically induced pressor responses by 5-HT (10 microg kg(-1) min(-1)) was unable to be elicited after i.v. treatment with methiothepin (100 microg kg(-1)) because of the marked inhibition produced by methiothepin alone. The 5-HT-induced inhibition was blocked after i.v. administration of WAY-100,635 (100 microg kg(-1)) and not affected by ritanserin (1 mg kg(-1)), MDL 72222 (2 mg kg(-1)). 5. The selective 5-HT(1A) receptor agonist, 8-hydroxydipropylaminotretalin hydrobromide (8-OH-DPAT) (5-20 microg kg(-1) min(-1)) but neither the rodent 5-HT(1B) receptor agonist, CGS-12066B (5 microg kg(-1) min(-1)), nor the selective nonrodent 5-HT(1B) and 5-HT(1D) receptor agonist, L-694,247 (5 and 40 microg kg(-1) min(-1)), inhibited the electrically induced pressor response. The selective 5-HT(1A) receptor antagonist, WAY-100,635 (100 microg kg(-1)), blocked the inhibition induced by 8-OH-DPAT (10 microg kg(-1) min(-1)). 8-OH-DPAT had no effect on exogenous NA-induced pressor responses. 6. Experimental diabetes produces changes in the inhibitory effect induced by 5-HT on electrically induced sympathetic pressor responses, such that the inhibitory action induced by 5-HT in diabetic pithed rats is mediated by prejunctional 5-HT(1A) receptors.

Citing Articles

Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT Receptor Activation via NO Pathway.

Fernandez-Gonzalez J, Garcia-Pedraza J, Ordonez J, Terol-Ubeda A, Martin M, Moran A Int J Mol Sci. 2023; 24(2).

PMID: 36674892 PMC: 9865738. DOI: 10.3390/ijms24021378.

Role of peripheral 5-HT receptors in 5-HT-induced cardiac sympatho-inhibition in type 1 diabetic rats.

Garcia-Pedraza J, Hernandez-Abreu O, Moran A, Carretero J, Garcia-Domingo M, Villalon C Sci Rep. 2020; 10(1):19358.

PMID: 33168874 PMC: 7652863. DOI: 10.1038/s41598-020-76298-6.

5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation.

Darios E, Barman S, Orer H, Morrison S, Davis R, Seitz B Eur J Pharmacol. 2015; 754:140-7.

PMID: 25732865 PMC: 4385506. DOI: 10.1016/j.ejphar.2015.02.032.

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