Chronic sarpogrelate treatment improves renal sympathetic hyperactivity in experimental diabetes.

Autor: Fernández-González JF; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca 37007, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, Salamanca 37007, Spain., García-Pedraza JÁ; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca 37007, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, Salamanca 37007, Spain., Terol-Úbeda AC; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca 37007, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, Salamanca 37007, Spain., Martín ML; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca 37007, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, Salamanca 37007, Spain., Morán A; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca 37007, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, Salamanca 37007, Spain., García-Domingo M; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca 37007, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, Salamanca 37007, Spain. Electronic address: mgarciad@usal.es.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Jul; Vol. 176, pp. 116814. Date of Electronic Publication: 2024 May 30.
DOI: 10.1016/j.biopha.2024.116814
Abstrakt: Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a modulator of renal sympathetic input and vascular tone. In this line, 5-HT 2 receptor blockade has been linked with reduced incidence and progression of diabetic microvascular alterations. In this work, we aimed to determine, in diabetic rats, whether 5-HT 2 blockade ameliorates renal function and to characterize the serotonergic modulatory action on renal sympathetic neurotransmission. Diabetes was induced in male Wistar rats by alloxan administration (150 mg/kg, s.c.), and sarpogrelate (30 mg/kg·day, p.o.; 5-HT 2 antagonist) was administered for 14 days (DM-S). Normoglycemic and diabetic (DM) animals were maintained as aged-matched controls. At 28th day, DM-S animals were anesthetized and prepared for the in situ autoperfusion of the kidney. Renal vasoconstrictor responses were induced electrically or by i.a. noradrenaline (NA) administration. The role of 5-HT and selective 5-HT agonist/antagonist were studied on these renal vasopressor responses. Sarpogrelate treatment decreased renal sympathetic-induced vasopressor responses, reduced renal hypertrophy and kidney damage markers increased in DM. Intraarterial 5-HT inhibited the sympathetic-induced renal vasoconstrictions, effect reproduced by 5-CT, AS-19, L-694,247 and LY 344864 (5-HT 1/5/7 , 5-HT 7 , 5-HT 1D and 5-HT 1F receptor agonists, respectively). Blocking 5-HT 1D/1F/7 receptors completely abolished the 5-CT sympatho-inhibition. NA vasoconstrictions were not altered by any of the 5-HT agonists tested. Thus, in experimental diabetes, chronic sarpogrelate treatment reduces renal damage markers, kidney hypertrophy and renal sympathetic hyperactivity and modifies serotonergic modulation of renal sympathetic neurotransmission, causing a sympatho-inhibition by prejunctional 5-HT 1D/1F and 5-HT 7 activation.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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