04363nam a22006977a 4500
150313s20142014 xxu||||| |||| 00| 0 eng d
0021-9150
Ovid MEDLINE(R)
24769306
PPAR activation does not affect endothelin activity in non-diabetic patients with hypertension or hypercholesterolemia.
Atherosclerosis. 234(2):436-40, 2014 Jun.
Atherosclerosis. 234(2):436-40, 2014 Jun.
Atherosclerosis
2014
FY2014
2015-03-17
CONCLUSIONS: In non-diabetic patients with hypertension or hypercholesterolemia, pioglitazone improves insulin sensitivity, lipid profile, and inflammation but does not affect endothelin activity. Our data suggest that the determinants of endothelin-1 vascular activity in vivo may differ and/or be more complex than those suggested by the results of previous in vitro studies.Copyright � 2014 Elsevier Ireland Ltd. All rights reserved.
METHODS: We conducted a single center, randomized, double-blind, placebo controlled, cross-over trial in 80 patients with either hypertension or hypercholesterolemia and further classified as insulin-sensitive or insulin-resistant based on a published insulin sensitivity index. Participants received pioglitazone 45 mg daily or matching placebo for eight weeks. The main endpoint was the change in forearm vascular endothelin-1 activity, as assessed by intra-arterial infusion of the endothelin type A receptor blocker BQ-123, measured at the end of each 8-week treatment period.
OBJECTIVES: This study tested the hypothesis that pioglitazone reduces endothelin-1 activity in the forearm vasculature in non-diabetic patients with hypertension or hypercholesterolemia and variable degrees of insulin resistance.
RESULTS: Pioglitazone lowered plasma insulin (P < 0.001), improved insulin sensitivity (P < 0.001), increased HDL (P < 0.001), and reduced triglycerides (P = 0.003), free fatty acids (P = 0.005), and C-reactive protein (P = 0.001). However, pioglitazone did not affect the vasodilator response to BQ-123 in the whole group (P = 0.618) and in the diagnosis or insulin sensitivity subgroups. Hence, in non-diabetic patients with hypertension or hypercholesterolemia, PPAR activation with pioglitazone does not affect endothelin-1 activity, despite enhancing insulin sensitivity and reducing plasma insulin and C-reactive protein levels.
English
*Endothelin-1/me [Metabolism]
*Endothelium, Vascular/de [Drug Effects]
*Forearm/bs [Blood Supply]
*Hypercholesterolemia/dt [Drug Therapy]
*Hypertension/dt [Drug Therapy]
*Insulin Resistance
*PPAR gamma/ag [Agonists]
*Thiazolidinediones/tu [Therapeutic Use]
Biological Markers/bl [Blood]
C-Reactive Protein/me [Metabolism]
Cross-Over Studies
District of Columbia
Double-Blind Method
Endothelin A Receptor Antagonists/ad [Administration & Dosage]
Endothelium, Vascular/me [Metabolism]
Endothelium, Vascular/pp [Physiopathology]
Fatty Acids, Nonesterified/bl [Blood]
Humans
Hypercholesterolemia/bl [Blood]
Hypercholesterolemia/pp [Physiopathology]
Hypertension/bl [Blood]
Hypertension/pp [Physiopathology]
Insulin/bl [Blood]
Lipoproteins, HDL/bl [Blood]
Peptides, Cyclic/ad [Administration & Dosage]
PPAR gamma/me [Metabolism]
Time Factors
Treatment Outcome
Triglycerides/bl [Blood]
Vasodilation/de [Drug Effects]
MedStar Heart & Vascular Institute
Journal Article
Randomized Controlled Trial
Campia, Umberto
Matuskey, Linda A
Panza, Julio A
Campia U, Cardillo C, Matuskey LA, Panza JA, Tesauro M
http://dx.doi.org/10.1016/j.atherosclerosis.2014.03.035
http://dx.doi.org/10.1016/j.atherosclerosis.2014.03.035
ART
Article
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Article
authcat
authcat
2015-03-17
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24769306
24769306
2015-03-17
2015-03-17
ART
1140
1140