Document Detail

Angiotensin blockade or calcium antagonists improve endothelial dysfunction in hypertension: studies in perfused mesenteric resistance arteries.
MedLine Citation:
PMID:  7528292     Owner:  NLM     Status:  MEDLINE    
Endothelial regulation of peripheral vascular resistance is impaired in hypertension. We studied the effects of different antihypertensive therapies on endothelial function in perfused mesenteric resistance arteries. Spontaneously hypertensive rats (SHR) aged 7 weeks were treated with either the nonpeptidic angiotensin II (AII) receptor antagonist CGP 48369, the angiotensin-converting enzyme (ACE) inhibitor benazepril HCl, or the calcium antagonist nifedipine (each 10 mg/kg/day orally, p.o.) for 8 weeks. All forms of therapy inhibited the increase in systolic blood pressure (SBP) to a comparable degree (18-23 mm Hg) and reduced but did not normalize medial hypertrophy in SHR. Changes in intraluminal vascular diameter to acetylcholine (ACh), norepinephrine (NE), and endothelin-1 (ET-1) were measured. Impaired endothelium-dependent relaxations to intraluminal ACh improved or normalized with all therapies, whereas the response to extraluminal ACh (which was unimpaired in SHR) remained unaffected. The endothelium-dependent inhibition of contractions to NE was lost in untreated SHR and improved or restored by antihypertensive therapy. In SHR, the sensitivity but not the maximal response of vascular smooth muscle (VSM) to ET-1 was paradoxically decreased. Antihypertensive therapy with CGP 48369, nifedipine, or benazepril HCl restored or increased the sensitivity to ET-1. Thus, chronic blockade of the renin-angiotensin system or voltage-operated calcium channels reduces BP and improves endothelial dysfunction in the resistance circulation of SHR. This may contribute to normalization of peripheral vascular resistance during antihypertensive treatment and improve local blood flow to vital organs.
Y Dohi; L Criscione; K Pfeiffer; T F Lüscher
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  24     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1995-01-25     Completed Date:  1995-01-25     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:  372-9     Citation Subset:  IM    
Department of Medicine, University Hospitals Basel, Switzerland.
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MeSH Terms
Acetylcholine / pharmacology
Angiotensin II / pharmacology,  therapeutic use
Antihypertensive Agents / pharmacology,  therapeutic use*
Benzazepines / pharmacology,  therapeutic use
Blood Pressure / drug effects*
Disease Models, Animal
Endothelins / pharmacology
Endothelium, Vascular / drug effects
Hypertension / drug therapy*,  physiopathology
Mesenteric Arteries
Muscle Contraction / drug effects
Muscle Relaxation / drug effects
Muscle, Smooth, Vascular / drug effects*
Nifedipine / pharmacology,  therapeutic use
Norepinephrine / pharmacology
Potassium Chloride / pharmacology
Rats, Inbred SHR
Rats, Inbred WKY
Receptors, Angiotensin / antagonists & inhibitors,  metabolism
Vascular Resistance / drug effects*
Reg. No./Substance:
0/Antihypertensive Agents; 0/Benzazepines; 0/Endothelins; 0/Pyrimidines; 0/Receptors, Angiotensin; 0/Tetrazoles; 11128-99-7/Angiotensin II; 135689-23-5/CGP 48369; 21829-25-4/Nifedipine; 51-41-2/Norepinephrine; 51-84-3/Acetylcholine; 7447-40-7/Potassium Chloride; 86541-75-5/benazepril

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

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