Document Detail


Carvedilol's actions are largely mediated by endogenous nitric oxide.
MedLine Citation:
PMID:  17190240     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Carvedilol's adrenergic antagonism does not fully explain its therapeutic actions. We therefore tested the hypothesis that its action is associated with an increase in NO synthesis. Wistar rats (male, 9 weeks, n = 10) anesthetized with sodium pentobarbital were used. Arterial NO concentration ([NO]), determined by chemiluminescence, and mean arterial pressure (MAP) were monitored throughout the experiment. In protocol 1), the effects of carvedilol (1 mg/kg, iv) were studied over a eriod of 90 min. In protocol 2), carvedilol was p administered, followed by the NO synthase (NOS) inhibitor L-NAME (5 mg/kg, iv) and by a second carvedilol administration. In protocol 1), carvedilol induced a significant fall in MAP (from 125,0 +/- 4,5 mmHg to 78.2 +/- 2.6 mmHg; p <0.001), reaching a minimum at t = 11.7 +/- 2.1 min and recovering 60 min afterwards (105.7 +/- 5.9 mmHg). Plasma [NO] varied in response to carvedilol in inverse proportion to MAP: baseline, 19.8 +/- 0.9 microM; t = 11.7 +/- 2.1 min, 32,3 +/- 2,3 microM; t = 60 min, 17.3 +/- 1.9 microM. In protocol 2), L-NAME administration blocked the effects of carvedilol (L-NAME: MAP, 129.9 +/- 5.0 mmHg; [NO], 13,1 +/- 2,3 microM. Post-L-NAME carvedilol administration resulted in MAP of 108.3 +/- 8.0 mmHg, NS, and [NO], 21.3 +/- 1.3 microM, NS. These results suggest that carvedilol increases plasma [NO], which is associated with a fall in MAP. Furthermore, carvedilol's hemodynamic action was blocked by NOS inhibition, suggesting that it depends on endogenous NO production, thus possibly explaining carvedilol's effects in hypertension and in cardiac failure.
Authors:
Ricardo A Afonso; Rita S Patarrão; Maria Paula Macedo; M Mota Carmo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Revista portuguesa de cardiologia : orgão oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology     Volume:  25     ISSN:  0870-2551     ISO Abbreviation:  Rev Port Cardiol     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-12-27     Completed Date:  2007-04-26     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  8710716     Medline TA:  Rev Port Cardiol     Country:  Portugal    
Other Details:
Languages:  eng     Pagination:  911-7     Citation Subset:  IM    
Affiliation:
Departamento de Bioquímica, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal. rafonso.biot@fcm.unl.pt
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MeSH Terms
Descriptor/Qualifier:
Animals
Antihypertensive Agents / pharmacology*
Blood Pressure / drug effects*
Carbazoles / pharmacology*
Male
Nitric Oxide / blood*
Nitric Oxide Synthase / antagonists & inhibitors
Propanolamines / pharmacology*
Rats
Rats, Wistar
Time Factors
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Carbazoles; 0/Propanolamines; 0K47UL67F2/carvedilol; 10102-43-9/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase

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