Document Detail

AT1 receptor antagonist treatment caused persistent arterial functional changes in young spontaneously hypertensive rats.
MedLine Citation:
PMID:  9403569     Owner:  NLM     Status:  MEDLINE    
The effects of chronic treatment with an AT1 receptor antagonist (L-158,809) on hypertension development and cardiovascular changes were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). L-158,809 treatment (0.6 mg/kg PO) was initiated at 3 weeks of age and lasted 12 weeks, to 15 weeks of age. The treatment prevented hypertension development in the SHR (systolic blood pressure, BP, of 136+/-1 mm Hg compared with 198+/-3 mm Hg in control SHR), and lowered the BP of WKY (99+/-2 vs 128+/-1 mm Hg in control WKY). Treatment significantly reduced the heart weight in SHR and WKY. Ten weeks after treatment withdrawal (25 weeks of age), BP had increased in SHR and WKY to 172+/-8 and 117+/-3 mm Hg, respectively. Body weight and kidney weight were not affected by the treatment. Mesenteric arteries from treated SHR were less responsive than control SHR arteries to periarterial nerve stimulations at transmural pressures higher than 80 mm Hg (15 and 25 weeks). Control WKY arteries were less responsive than control SHR arteries at almost all transmural pressures tested (15 weeks) and to pressures greater than 80 mm Hg (25 weeks). Pretreatment of arteries with 10(-8) mol/L angiotensin II enhanced their response to nerve stimulation in vessels from control SHR and WKY (25 weeks) but not from treatment-withdrawn SHR and WKY. Treatment did not alter arterial reactivity in response to norepinephrine. Alteration in arterial structure due to L-158,809 treatment was found only when measured at a transmural pressure of 100 mm Hg. In conclusion, L-158,809 was effective in preventing hypertension during the treatment period, in reducing hypertension severity during the withdrawal period, and in persistently decreasing the reactivity of the arteries.
L K Gillies; M Lu; H Wang; R M Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  30     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-01-08     Completed Date:  1998-01-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1471-8     Citation Subset:  IM    
Smooth Muscle Research Programme and Department of Anaesthesia, McMaster University, Hamilton, Ontario, Canada.
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MeSH Terms
Angiotensin II / pharmacology
Antihypertensive Agents / pharmacology*
Blood Pressure / drug effects*
Body Weight / drug effects
Electric Stimulation
Heart / drug effects,  physiology,  physiopathology
Hypertension / physiopathology*,  prevention & control
Imidazoles / pharmacology*
Kidney / drug effects
Mesenteric Arteries / drug effects*,  innervation,  physiology
Muscle, Smooth, Vascular / drug effects*,  innervation,  physiology
Organ Size / drug effects
Rats, Inbred SHR
Rats, Inbred WKY
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin / antagonists & inhibitors*
Tetrazoles / pharmacology*
Reg. No./Substance:
0/Antihypertensive Agents; 0/Imidazoles; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Receptors, Angiotensin; 0/Tetrazoles; 11128-99-7/Angiotensin II; 135145-96-9/L 158809

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

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