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

MedStar author(s):
Citation: Atherosclerosis. 234(2):436-40, 2014 Jun.PMID: 24769306Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Randomized Controlled TrialSubject headings: *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]Year: 2014ISSN:
  • 0021-9150
Name of journal: AtherosclerosisAbstract: 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.All authors: Campia U, Cardillo C, Matuskey LA, Panza JA, Tesauro MFiscal year: FY2014Digital Object Identifier: Date added to catalog: 2015-03-17
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Journal Article MedStar Authors Catalog Article 24769306 Available 24769306

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.

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