Effect of sarpogrelate treatment on 5-HT modulation of vascular sympathetic innervation and platelet activity in diabetic rats.

Autor: Fernández-González JF; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain., García-Pedraza JÁ; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain., Marín-Quílez A; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain; Departamento de Hematología, Complejo Asistencial Universitario de Salamanca (CAUSA), 37007 Salamanca, Spain., Bastida JM; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain; Departamento de Hematología, Complejo Asistencial Universitario de Salamanca (CAUSA), 37007 Salamanca, Spain., Martín ML; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain., Morán A; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain., García-Domingo M; Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain. Electronic address: mgarciad@usal.es.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Sep; Vol. 153, pp. 113276. Date of Electronic Publication: 2022 Jun 16.
DOI: 10.1016/j.biopha.2022.113276
Abstrakt: This study aimed to investigate whether the 5-HT 2 receptor blockade alters the 5-HT effect on vascular sympathetic neurotransmission and platelet activation in type 1 diabetes. 28-day diabetes was obtained by alloxan (150 mg/kg; s.c.) in male Wistar rats, administering sarpogrelate (5-HT 2 blocker; 30 mg/kg/day; p.o.) for 14 days. Blood glucose and body weight were monitored for 28 days. After 4 weeks of diabetes induction, food and drink intake, urine, plasma-platelet 5-HT, and platelet activation were determined in normoglycemic, non-treated diabetic and sarpogrelate-treated diabetic rats. Another set of diabetic rats were pithed to run the vascular sympathetic stimulation or exogenous noradrenaline administration, examining the induced vasoconstrictor responses. Sarpogrelate treatment significantly reduced drink intake and urine, whereas BW gain, hyperglycemia, and food intake were not modified in diabetic rats. The platelet activation and plasma 5-HT concentration were decreased (increasing the stored 5-HT platelet) by 5-HT 2 blockade in diabetic animals. The sympathetic-induced vasoconstrictions were higher in non-treated than in sarpogrelate-treated diabetic rats. 5-HT inhibited these vasopressor responses, reproduced exclusively by the 5-HT 1/5/7 receptor agonist, 5-CT. The 5-CT-produced inhibition was partly reversed by 5-HT 1D or 5-HT 7 antagonists (LY310762 or SB-258719, respectively), and totally annulled by the mixture of LY310762+SB-258719. Noradrenaline-caused vasoconstrictions were also decreased by 5-CT. In conclusion, our results reveal that 14-day sarpogrelate treatment improves polydipsia and polyuria, reduces platelet hyperactivation, plasma 5-HT and the vascular sympathetic tone, and changes 5-HT receptors inhibiting noradrenergic drive in diabetic rats: pre and/or postjunctional 5-HT 1D/7 are involved in the sympatho-inhibition.
Competing Interests: Conflict of interest statement The authors declare that there are no conflicts of interests.
(Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: