TY  - BOOK
AU  - Campia, Umberto
AU  - Matuskey, Linda A
AU  - Panza, Julio A
TI  - PPAR activation does not affect endothelin activity in non-diabetic patients with hypertension or hypercholesterolemia
SN  - 0021-9150
PY  - 2014///
KW  - *Endothelin-1/me [Metabolism]
KW  - *Endothelium, Vascular/de [Drug Effects]
KW  - *Forearm/bs [Blood Supply]
KW  - *Hypercholesterolemia/dt [Drug Therapy]
KW  - *Hypertension/dt [Drug Therapy]
KW  - *Insulin Resistance
KW  - *PPAR gamma/ag [Agonists]
KW  - *Thiazolidinediones/tu [Therapeutic Use]
KW  - Biological Markers/bl [Blood]
KW  - C-Reactive Protein/me [Metabolism]
KW  - Cross-Over Studies
KW  - District of Columbia
KW  - Double-Blind Method
KW  - Endothelin A Receptor Antagonists/ad [Administration & Dosage]
KW  - Endothelium, Vascular/me [Metabolism]
KW  - Endothelium, Vascular/pp [Physiopathology]
KW  - Fatty Acids, Nonesterified/bl [Blood]
KW  - Humans
KW  - Hypercholesterolemia/bl [Blood]
KW  - Hypercholesterolemia/pp [Physiopathology]
KW  - Hypertension/bl [Blood]
KW  - Hypertension/pp [Physiopathology]
KW  - Insulin/bl [Blood]
KW  - Lipoproteins, HDL/bl [Blood]
KW  - Peptides, Cyclic/ad [Administration & Dosage]
KW  - PPAR gamma/me [Metabolism]
KW  - Time Factors
KW  - Treatment Outcome
KW  - Triglycerides/bl [Blood]
KW  - Vasodilation/de [Drug Effects]
KW  - MedStar Heart & Vascular Institute
KW  - Journal Article
KW  - Randomized Controlled Trial
N2  - 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
UR  - http://dx.doi.org/10.1016/j.atherosclerosis.2014.03.035
ER  -