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Oral fluoxetine treatment changes serotonergic sympatho-regulation in experimental type 1 diabetes.
- Source :
-
Life sciences [Life Sci] 2022 Mar 15; Vol. 293, pp. 120335. Date of Electronic Publication: 2022 Jan 18. - Publication Year :
- 2022
-
Abstract
- Aims: This study investigated whether fluoxetine treatment changes the 5-HT regulation on vascular sympathetic neurotransmission in type 1 diabetes.<br />Main Methods: Four-week diabetes was obtained by a single alloxan s.c. administration in male Wistar rats, administering fluoxetine for 14 days (10 mg/kg/day; p.o.). Systolic blood pressure, heart rate, glycaemia, body weight (BW) evolution, creatinine, and blood urea nitrogen (BUN) were monitored. Afterward, rats were pithed to perform the vascular sympathetic stimulation. 5-HT <subscript>1A/1D/2A</subscript> receptors expression was analysed by Western blot in thoracic aorta. Both i.v. norepinephrine and the electrical stimulation of the spinal sympathetic drive evoked vasoconstrictor responses.<br />Key Findings: Fluoxetine treatment significantly reduced the BW gain, hyperglycaemia, creatinine, and BUN in diabetic rats. The electrical-produced vasopressor responses were greater in untreated than in fluoxetine-treated diabetic rats. 5-HT decreased the sympathetic-produced vasopressor responses. While 5-CT, 8-OH-DPAT and L-694,247 (5-HT <subscript>1/7</subscript> , 5-HT <subscript>1A</subscript> and 5-HT <subscript>1D</subscript> agonists, respectively) reproduced 5-HT-evoked inhibition, the 5-HT <subscript>2</subscript> activation by α-methyl-5-HT augmented the vasoconstrictions. The 5-CT sympatho-inhibition was reversed by 5-HT <subscript>1A</subscript> plus 5-HT <subscript>1D</subscript> antagonists (WAY-100,635 and LY310762, respectively), whereas ritanserin (5-HT <subscript>2A</subscript> antagonist) blocked the α-methyl-5-HT potentiating effect. Norepinephrine-generated vasoconstrictions were increased or diminished by α-methyl-5-HT or 5-CT, respectively. 5-HT <subscript>1A/1D/2A</subscript> receptors were expressed at vascular level, being 5-HT <subscript>1A</subscript> expression increased by fluoxetine in diabetic rats.<br />Significance: Our findings suggest that fluoxetine improves metabolic and renal profiles, changes the vasopressor responses, and 5-HT receptors modulating sympathetic activity in diabetic rats: 5-HT <subscript>1A/1D</subscript> are involved in the sympatho-inhibition, while 5-HT <subscript>2A</subscript> is implicated in the sympatho-potentiation, being both effects pre and/or postjunctional in nature.<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Administration, Oral
Animals
Blood Pressure drug effects
Blood Pressure physiology
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Type 1 drug therapy
Male
Rats
Rats, Wistar
Serotonin Antagonists pharmacology
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Type 1 metabolism
Fluoxetine administration & dosage
Receptors, Serotonin metabolism
Serotonin metabolism
Selective Serotonin Reuptake Inhibitors administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 293
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35051421
- Full Text :
- https://doi.org/10.1016/j.lfs.2022.120335