Document Detail

Vascular endothelin-1 expression and effect of an endothelin ETA antagonist on structure and function of small arteries from stroke-prone spontaneously hypertensive rats.
MedLine Citation:
PMID:  9595467     Owner:  NLM     Status:  MEDLINE    
There is some evidence that the endothelin (ET) system may participate in blood pressure elevation and in vascular hypertrophy in stroke-prone spontaneously hypertensive rats (SHR-SP). To further understand the involvement of the ET system in this hypertensive model, we examined preproendothelin-1 (preproET-1) mRNA abundance in blood vessels of 5-week and 18-week SHR-SP in comparison to SHR, and treated 12-week old SHR-SP with the ETA-selective receptor antagonist A-127722.5 (30 mg/kg/day in the drinking water) for 10 weeks. Abundance of preproET-1 mRNA by Northern blot analysis was increased more than twofold in aorta and mesenteric arteries of SHR-SP relative to SHR at 18 weeks but not at 5 weeks of age. SHR-SP treated with A-127722.5 had a tail-cuff systolic blood pressure at 22 weeks of age of 241 +/- 2 mm Hg vs. 251 +/- 3 mm Hg in untreated SHR-SP (p < 0.05). Heart:body weight ratio was no different in both groups, but aortic segment:body weight ratio was slightly but significantly smaller in treated SHR-SP (p < 0.05). Pressurized mesenteric small arteries from treated SHR-SP had a smaller media width (12.6 +/- 0.6 microns vs. 14.9 +/- 0.5 microns; p < 0.05) and media:lumen ratio (5.8 +/- 0.2% vs. 7.3 +/- 0.3%; p < 0.01), whereas media cross-sectional area and lumen diameter tended to decrease and increase, respectively, without achieving statistical significance. Acetylcholine-induced relaxation was improved in treated SHR-SP (99.6 +/- 0.6% vs. 90.0 +/- 3.6%; p < 0.05), whereas relaxation responses to sodium nitroprusside were similar in both groups. These results show increases of preproET-1 expression in blood vessels that appear to be secondary to blood pressure elevation. There is a small ET-dependent component in blood pressure elevation and in conduit and resistance artery changes in adult stroke-prone SHR.
A M Sharifi; G He; R M Touyz; E L Schiffrin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  31 Suppl 1     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1998  
Date Detail:
Created Date:  1998-07-17     Completed Date:  1998-07-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  S309-12     Citation Subset:  IM    
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
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MeSH Terms
Blood Pressure / drug effects
Blood Vessels / metabolism*
Blotting, Northern
Endothelin-1 / biosynthesis*
Hypertension / genetics,  pathology*,  physiopathology*
Mesenteric Arteries / drug effects,  pathology*,  physiopathology*
Muscle Contraction / drug effects
Organ Size / drug effects
Pyrrolidines / pharmacology*
RNA, Messenger / biosynthesis
Rats, Inbred SHR
Receptor, Endothelin A
Receptors, Endothelin / antagonists & inhibitors*
Reg. No./Substance:
0/A 127722; 0/Endothelin-1; 0/Pyrrolidines; 0/RNA, Messenger; 0/Receptor, Endothelin A; 0/Receptors, Endothelin

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

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