Document Detail


Effects of glitazones on blood pressure and vascular structure in mesenteric resistance arteries and basilar artery from genetically hypertensive rats.
MedLine Citation:
PMID:  16405447     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The effects of two of the glitazone (thiazolidinedione) class of drugs, namely rosiglitazone and pioglitazone, on blood pressure and vascular remodelling in the New Zealand genetically hypertensive (GH) rat model were investigated. 2. In the first study, a GH group given rosiglitazone (5 mg/kg per day) from the age of 7 to 12 weeks was compared with a GH control group. In the second study, GH rats were given either pioglitazone, simvastatin, valsartan or combinations of pioglitazone with simvastatin or valsartan (all drugs at a dose of 10 mg/kg per day). 3. Tail-cuff systolic blood pressure was measured weekly. At the end of the experiment, blood vessels were fixed by perfusion and samples of mesenteric resistance arteries (MRA), second-order branches and basilar artery were embedded in Technovit and serial sections were cut and stained with Giemsa for stereological analysis. Media width, medial cross-sectional area and lumen diameter were determined and the ratio of media width/lumen diameter was calculated. 4. Rosiglitazone significantly reduced blood pressure in GH rats. 5. In MRA, rosiglitazone had a hypotrophic effect on media, reduced lumen diameter and reduced media/lumen ratio (P<0.001). 6. In basilar artery, there was also a hypotrophic effect of rosiglitazone on media and reduced media/lumen ratio (P<0.001). 7. Pioglitazone slowed down the rate of blood pressure increase with age in GH rats and had a greater effect on blood pressure when given in combination with simvastatin. 8. Pioglitazone had a hypotrophic effect on the media of MRA and basilar artery. The hypotrophic effect was enhanced when pioglitazone was given in combination with simvastatin. The media/lumen ratio was reduced by pioglitazone; in MRA, combination treatment with simvastatin reduced the ratio further to normal and, with valsartan, to below normal. In basilar artery, the media/lumen ratio was reduced further by both combination treatments, but was lowest in the pioglitazone-valsartan combination group. 9. The significant effects on MRA and basilar artery structure (and, thus, haemodynamics) seen after rosiglitazone monotherapy and after pioglitazone, given alone and in combination with simvastatin or valsartan, may well indicate a glitazone class effect on vascular structure and, hence, cardiovascular function.
Authors:
Janet M Ledingham; Richard Laverty
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  32     ISSN:  0305-1870     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2006-01-12     Completed Date:  2006-09-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  919-25     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand. janet.ledingham@stonebow.otago.ac.nz
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II Type 1 Receptor Blockers
Animals
Basilar Artery / drug effects*,  pathology
Blood Pressure / drug effects*
Disease Models, Animal
Drug Therapy, Combination
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
Hypertension / drug therapy,  genetics,  pathology
Hypertrophy, Left Ventricular / drug therapy
Mesenteric Arteries / drug effects*,  pathology
Rats
Rats, Inbred SHR
Rats, Wistar
Simvastatin / administration & dosage
Tetrazoles / administration & dosage
Thiazolidinediones / administration & dosage,  pharmacology*
Tunica Media / drug effects,  pathology
Valine / administration & dosage,  analogs & derivatives
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Tetrazoles; 0/Thiazolidinediones; 111025-46-8/pioglitazone; 122320-73-4/rosiglitazone; 137862-53-4/valsartan; 7004-03-7/Valine; 79902-63-9/Simvastatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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