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Imidazolines as single agent therapy for diabetics with hypertension
Author(s) -
Edwards Lincoln Paul,
Crane Louis,
BaziardMouysset Genevieve,
BrownBryan TerryAnn
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.597.3
Subject(s) - moxonidine , imidazoline receptor , pharmacology , blood pressure , medicine , hek 293 cells , combination therapy , glycemic , endocrinology , compliance (psychology) , diabetes mellitus , chemistry , receptor , agonist , psychology , social psychology
Pharmacologic treatment of many diabetics also involves treating hypertension. This requires taking multiple drugs, which increases the risk of drug interaction, and decrease compliance and glycemic control. Imidazoline compounds have the potential to act as single agent therapy to treat diabetics with hypertension, thereby positively impacting compliance. We hypothesize that imidazoline compounds act centrally to lower blood pressure and decrease hyperglycemia by stimulating glucose uptake. Moxonidine (5nmol) and S43126 (5nmol), were injected cumulatively into the brain of spontaneously hypertensive rats, followed by measurement of blood pressure. HEK 293 kidney cells were treated with moxonidine (1μM) and glucose uptake measured. The imidazoline receptor antisera selective (IRAS) protein was overexpressed in HEK 293 cells, followed by treatment with moxonidine. Western blot was used to determine the phosphorylation of protein kinase B. Our results showed that both S43126 and moxonidine lowered arterial pressure by 20mmHg and 45mmHg respectively. Moxonidine caused a greater than 6 fold increase in glucose uptake at 60 min of treatment in HEK 293 cells. Cells overexpressing the IRAS protein showed a greater phosphorylation of PKB after treatment with moxonidine. These data suggest that imidazoline compounds may be developed as alternative therapy to treat diabetics with hypertension.