Document Detail


Inhibition of nitric oxide synthase and soluble guanylate cyclase induces cardiodepressive effects in normal rat hearts.
MedLine Citation:
PMID:  9369347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exogenous nitric oxide (NO) has been shown to modulate the contractile force of rat cardiac myocytes. We sought to determine whether endogenous NO-production in the isolated normal rat heart has an effect on myocardial contractility. Hearts of male Wistar rats were investigated using a constant flow perfused non-paced Langendorff preparation. Changes of contractile parameters such as left ventricular peak pressure, dP/dtmax and dP/dtmin, and of coronary perfusion pressure and heart rate were recorded after infusion of the NO-synthase inhibitors N(omega)-nitro-L-arginine (L-NOARG, 0.1 mM, 1.0 mM, n = 6), N(omega)-methyl-L-arginine (L-NMMA, 0.1 mM, 1.0 mM, n = 9) and methylene blue (2 microM, 20 microM, n = 6), the NO-donor sodium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolat (DEA/NO, 0.01 microM, 0.1 microM, n = 12), the specific inhibitor of soluble guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 0.1 microM, n = 7) and L-arginine (0.1 mM, 1.0 mM, n = 6). All NO-synthase inhibitors reduced the contractile function of the ventricular muscle before changes in coronary perfusion pressure were evident. The negative inotropic effect of L-NMMA was absent in the presence of an equimolar concentration of L-arginine. ODQ reduced contractile force and coronary perfusion pressure in parallel. By contrast, L-arginine and DEA/NO improved the contractile force of the left ventricle and DEA/NO decreased coronary perfusion pressure. Heart rate was reduced by L-NOARG (1 mM) and methylene blue (20 microM), while DEA/NO (0.1 microM) and L-arginine (1 mM) had a positive chronotropic effect. All these changes were significant (P < 0.05). These results suggest that endogenous NO-production exerts a positive effect on myocardial contraction that is mediated by activation of guanylate cyclase. In addition, NO might be involved in regulation of heart rate.
Authors:
G Kojda; K Kottenberg; E Noack
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  334     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1998-01-22     Completed Date:  1998-01-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  181-90     Citation Subset:  IM    
Affiliation:
Institut für Pharmakologie, Medizinische Einrichtungen, Heinrich-Heine-Universität, Düsseldorf, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Circulation / drug effects
Depression, Chemical
Guanylate Cyclase / antagonists & inhibitors*
Heart Rate / drug effects
Male
Myocardial Contraction / drug effects*
Myocardium / enzymology*
Nitric Oxide / antagonists & inhibitors,  pharmacology
Nitric Oxide Synthase / antagonists & inhibitors*
Rats
Rats, Wistar
Solubility
Chemical
Reg. No./Substance:
10102-43-9/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase; EC 4.6.1.2/Guanylate Cyclase

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