Beneficial effects of non-quinazoline α
Adipose Tissue
/ drug effects
Adrenergic alpha-1 Receptor Antagonists
/ pharmacokinetics
Animals
Antihypertensive Agents
/ pharmacokinetics
Biomarkers
/ blood
Blood Glucose
/ drug effects
Blood Pressure
/ drug effects
Disease Models, Animal
Endothelium, Vascular
/ drug effects
Energy Metabolism
/ drug effects
Fructose
Hypertension
/ drug therapy
Lipid Peroxidation
/ drug effects
Lipids
/ blood
Male
Metabolic Syndrome
/ blood
Piperazines
/ pharmacokinetics
Prazosin
/ pharmacology
Rats, Wistar
Tumor Necrosis Factor-alpha
/ blood
Fructose-fed rats
Hypertension
Metabolic syndrome
NO
TNF-α
α(1)-adrenoceptor antagonist
Journal
Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
07
09
2018
revised:
13
02
2019
accepted:
03
04
2019
pubmed:
28
5
2019
medline:
5
3
2020
entrez:
29
5
2019
Statut:
ppublish
Résumé
Metabolic syndrome associated with insulin resistance and hypertension is often caused by excessive fructose consumption. Treatment of hypertension in patients with metabolic syndrome is a difficult task as many antihypertensive drugs have adverse effects on the metabolic profile. We investigated if MH-76 and MH-79, non-quinazoline α Male rats were divided into 5 groups (n = 8) and studied for 18 weeks: group control: standard diet and drinking water; group Fructose: high-fructose diet (20% fructose in drinking water); groups Fructose + MH-76, Fructose + MH-79, Fructose + prazosin: high-fructose diet with subsequent MH-76, MH-79 (5 mg/kg/day ip) or prazosin (0.2 mg/kg/day ip) treatment 12 weeks later. In addition to their antihypertensive effect, the studied compounds reversed endothelial dysfunction, decreased hyperglycemia and hypertriglyceridemia, as well as prevented abdominal adiposity. Moreover, MH-76 reduced insulin resistance and decreased TNF-α concentration and lipid peroxidation in adipose tissue. Prazosin treatment exerted an antihypertensive effect, reduced hyperglycemia but did not improve endothelial dysfunction, insulin resistance, and abdominal adiposity. The lower efficacy of prazosin may be the result of its short half-time and the lack of described pleiotropic effects. α
Sections du résumé
BACKGROUND AND AIMS
Metabolic syndrome associated with insulin resistance and hypertension is often caused by excessive fructose consumption. Treatment of hypertension in patients with metabolic syndrome is a difficult task as many antihypertensive drugs have adverse effects on the metabolic profile. We investigated if MH-76 and MH-79, non-quinazoline α
METHODS AND RESULTS
Male rats were divided into 5 groups (n = 8) and studied for 18 weeks: group control: standard diet and drinking water; group Fructose: high-fructose diet (20% fructose in drinking water); groups Fructose + MH-76, Fructose + MH-79, Fructose + prazosin: high-fructose diet with subsequent MH-76, MH-79 (5 mg/kg/day ip) or prazosin (0.2 mg/kg/day ip) treatment 12 weeks later. In addition to their antihypertensive effect, the studied compounds reversed endothelial dysfunction, decreased hyperglycemia and hypertriglyceridemia, as well as prevented abdominal adiposity. Moreover, MH-76 reduced insulin resistance and decreased TNF-α concentration and lipid peroxidation in adipose tissue. Prazosin treatment exerted an antihypertensive effect, reduced hyperglycemia but did not improve endothelial dysfunction, insulin resistance, and abdominal adiposity. The lower efficacy of prazosin may be the result of its short half-time and the lack of described pleiotropic effects.
CONCLUSIONS
α
Identifiants
pubmed: 31133498
pii: S0939-4753(19)30117-6
doi: 10.1016/j.numecd.2019.04.003
pii:
doi:
Substances chimiques
Adrenergic alpha-1 Receptor Antagonists
0
Antihypertensive Agents
0
Biomarkers
0
Blood Glucose
0
Lipids
0
MH-76 compound
0
MH-79 compound
0
Piperazines
0
Tumor Necrosis Factor-alpha
0
Fructose
30237-26-4
Prazosin
XM03YJ541D
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
751-760Informations de copyright
Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.