Coronary vascular responsiveness to adenosine is impaired additively by blockade of nitric oxide synthesis and a sulfonylurea.
J Am Coll Cardiol
; 31(4): 816-22, 1998 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-9525553
ABSTRACT
OBJECTIVES:
We sought to define effects of glibenclamide, a sulfonylurea known to block ATP-dependent potassium (KATP) channels, and Nomega-nitro-L-arginine methyl ester (L-NAME), an L-arginine analog known to block nitric oxide (NO) synthesis, on coronary vascular responsiveness to adenosine.BACKGROUND:
The role of adenosine in coronary flow regulation becomes increasingly important when KATP channel function or NO synthesis is impaired. Both variables are potentially altered in patients with coronary artery disease taking a sulfonylurea.METHODS:
Dose-response curves relating coronary conductance to plasma adenosine concentration were obtained by using intracoronary infusions of adenosine (10 to 1,000 microg/min) in chronically instrumented dogs.RESULTS:
ED50, the plasma concentration of adenosine needed to produce 50% of the maximal increase in conductance under baseline conditions, increased threefold after either 1 or 10 mg/kg of L-NAME. ED50 also increased in response to glibenclamide in a dose-related fashion (5.7-fold increase per 1 mg/kg body weight of glibenclamide). Effects of combined blockade of KATP channels and NO synthesis were additive, with increases in ED50 as high as 15-fold. Both L-NAME and glibenclamide increased systemic pressure and reduced coronary conductance, confirming the roles of NO and KATP channels in regulating coronary and systemic vascular tone under rest conditions as well as during stress.CONCLUSIONS:
Coronary vascular responsiveness to adenosine is blunted in vivo by both L-NAME and glibenclamide. Effects of the sulfonylurea and blockade of NO synthesis are additive and can limit coronary vasodilation as well as other responses involving KATP channels and NO.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatação
/
Vasodilatadores
/
Adenosina
/
Glibureto
/
Vasos Coronários
/
Óxido Nítrico
Limite:
Animals
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article