PPAR activation does not affect endothelin activity in non-diabetic patients with hypertension or hypercholesterolemia.
PPAR activation does not affect endothelin activity in non-diabetic patients with hypertension or hypercholesterolemia.
- 2014
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
0021-9150
*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
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
0021-9150
*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