Document Detail


In vivo characterization of muscarinic receptor subtypes that mediate vasodilatation in patients with essential hypertension.
MedLine Citation:
PMID:  7607735     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Attenuated cholinergic vasodilatation has been suggested as an endothelium-related mechanism involved in essential hypertension. We investigated the role of muscarinic (M) receptor subtypes in the forearm resistance vasculature. In eight white men with essential hypertension and eight matched normotensive control subjects (age of both groups, 47 +/- 4 years; mean +/- SEM), we infused the nonselective agonist methacholine in the presence of saline and the antagonists atropine (nonselective), pirenzepine (M1-selective), and AF-DX 116 (M2-selective) into the brachial artery and measured forearm blood flow and forearm vascular resistance using venous occlusion plethysmography. Affinity constants (pKb values) were determined from calculated plasma concentrations of the infused compounds and EC50 values. Sodium nitroprusside was given as an endothelium-independent control, and minimal forearm vascular resistance after 10 minutes of ischemia was used as a marker of structural vascular changes. Hypertensive patients showed higher minimal forearm vascular resistance, indicating structural vascular changes. However, sodium nitro-prusside- and methacholine-induced vasodilatation was similar in both groups, with apparent EC50 values (log moles per liter; mean +/- SEM) of -7.32 +/- 0.13 and -7.51 +/- 0.21 in hypertensive patients and -7.37 +/- 0.13 and -7.45 +/- 0.02 in control subjects, respectively. Atropine, pirenzepine, and AF-DX 116 caused a shift to the right of the concentration-response curve of methacholine, with apparent pKb values of 8.63 +/- 0.08, 6.81 +/- 0.13, and 5.51 +/- 0.29 in hypertensive individuals and 8.62 +/- 0.10, 6.98 +/- 0.08, and 5.49 +/- 0.09 in control subjects, respectively. Again, there were no statistically significant differences in these pharmacological parameters between hypertensive patients and normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
T A Bruning; P C Chang; M G Hendriks; P Vermeij; M Pfaffendorf; P A van Zwieten
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Controlled Clinical Trial; Journal Article    
Journal Detail:
Title:  Hypertension     Volume:  26     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1995 Jul 
Date Detail:
Created Date:  1995-08-14     Completed Date:  1995-08-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  70-7     Citation Subset:  IM    
Affiliation:
Department of Nephrology, University Hospital Leiden, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Atropine / pharmacology
Forearm / blood supply
Humans
Hypertension / physiopathology*
Male
Methacholine Chloride / pharmacology
Middle Aged
Nitroprusside / pharmacology
Parasympatholytics / pharmacology
Pirenzepine / analogs & derivatives,  pharmacology
Plethysmography
Receptors, Muscarinic / classification,  physiology*
Vasodilation* / drug effects
Chemical
Reg. No./Substance:
0/Parasympatholytics; 0/Receptors, Muscarinic; 102394-31-0/otenzepad; 15078-28-1/Nitroprusside; 28797-61-7/Pirenzepine; 51-55-8/Atropine; 62-51-1/Methacholine Chloride

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


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