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. 2016 Sep 23:6:33979.
doi: 10.1038/srep33979.

Blocking 5-HT2 receptor restores cardiovascular disorders in type 1 experimental diabetes

José-Ángel García-Pedraza  1   2 , Pedro Ferreira-Santos  1   2 , Rubén Aparicio  1   2 , María-José Montero  1   2 , Asunción Morán  1   2
Affiliations

Blocking 5-HT2 receptor restores cardiovascular disorders in type 1 experimental diabetes

José-Ángel García-Pedraza et al. Sci Rep. .

Abstract

This study aimed to determine whether the serotonergic modulation, through selective 5-HT2 receptor blockade, restores cardiovascular disturbances in type 1 diabetic rats. Diabetes was induced by alloxan (150 mg/kg, s.c.) and maintained for 4 weeks. 5-HT2 receptor was blocked by sarpogrelate (30 mg/kg.day; 14 days; p.o.). Systolic blood pressure (SBP), heart rate (HR), glycaemia and body weight (BW) were monitored periodically. Animals were sacrificed at the end of the study and the heart, right kidney and thoracic aorta were removed; plasma samples were also obtained. Left ventricular hypertrophy index (LVH) and renal hypertrophy index (RH) were determined. Vascular function was studied in aorta rings; additionally, superoxide anion (O2•-) production (by lucigenin-enhanced chemiluminescence) and lipid peroxidation (by thiobarbituric acid reactive substances assay) were measured. Neither alloxan nor sarpogrelate treatments altered HR, LVH or endothelium-independent relaxation. SBP, glycaemia, BW, RH, O2•- production and lipid peroxidation were significantly altered in diabetic animals compared with controls. Sarpogrelate treatment considerably decreased SBP, RH, O2•- production and lipid peroxidation. Endothelium-dependent relaxation was severely reduced in diabetic animal aortas compared to controls; sarpogrelate treatment markedly improved it. Our outcomes show that selectively blocking 5-HT2 receptors has beneficial effects on impaired cardiovascular parameters in diabetes.

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Figures

Figure 1
Figure 1. Cardiac and renal hypertrophy.
Relation between the weight of the left ventricle (A) or the weight of kidney (B) and the tibia length, used as left ventricular hypertrophy index (LVH) or renal hypertrophy index (RH), respectively, in normoglycaemic group (Control), diabetic group (D) and sarpogrelate-treated diabetic group (D+Sarp). Values are expressed as mean ± SEM (n = 5–8). *P < 0.05 vs control group. #P < 0.05 vs diabetic group.
Figure 2
Figure 2. Aortic endothelium-dependent relaxation.
Relaxation induced by acetylcholine (ACh) in aorta from normoglycaemic group (Control), diabetic group (D) and sarpogrelate-treated diabetic group (D+Sarp). Values are expressed as mean ± SEM (n = 8 each). *P < 0.05 vs control group. #P < 0.05 vs diabetic group.
Figure 3
Figure 3. NO, COX and endothelium-derived hyperpolarization pathways in aortic endothelium-dependent relaxation.
Concentration–response curves to acetylcholine (ACh) in the presence of: (A) indomethacin (10−5 M) plus TEA (10−4 M), (B) L-NAME (10−4 M) plus TEA, or (C) L-NAME plus indomethacin in aorta from normoglycaemic group (Control), diabetic group (D) and sarpogrelate-treated diabetic group (D+Sarp). Values are expressed as mean ± SEM (n = 3–5). *P < 0.05 vs control group. #P < 0.05 vs diabetic group.
Figure 4
Figure 4. Aortic endothelium-independent relaxation.
Vascular relaxation to sodium nitroprusside (SNP) in aorta from normoglycaemic group (Control), diabetic group (D) and sarpogrelate-treated diabetic group (D+Sarp). Values are expressed as mean ± SEM (n = 4–7).
Figure 5
Figure 5. Superoxide anion determination.
Vascular superoxide anion (O2•−) level expressed as relative luminescence units (RLU)/min/mg dry tissue stimulated by NADPH addition in aortic rings from normoglycaemic group (Control), diabetic group (D) and sarpogrelate-treated diabetic group (D+Sarp). Values are expressed as mean ± SEM (n = 6). *P < 0.05 vs control group. #P < 0.05 vs diabetic group.
Figure 6
Figure 6. Lipid peroxidation determination.
Plasmatic malondialdehyde (MDA) concentration (nmol/ml) from normoglycaemic group (Control), diabetic group (D) and sarpogrelate-treated diabetic group (D+Sarp). Values are expressed as mean ± SEM (n = 4–7). *P < 0.05 vs control group. #P < 0.05 vs diabetic group.
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