Role of XXXX in parasympathetic modulation of beta-adrenergic myocardial contractility in normal @entity235 .

@entity452 @entity235 @entity534 @entity8263 @entity7293 @entity842 @entity3897
In vitro studies indicate that muscarinic cholinergic inhibition of beta-adrenergic cardiac responses may be modulated in part by @entity842 (NO). To evaluate the role of NO in parasympathetic inhibition of the beta-adrenergic contractile response in vivo, we assessed the inotropic response to @entity452 before and during bilateral vagus nerve stimulation in closed-chest @entity235 . @entity452 administration and vagal stimulation were repeated during intracoronary infusion of the NO synthase inhibitor @entity7293 ( @entity7293 , 10 mumol/min) and again following infusion of @entity534 (100 mg/kg). In eight @entity235 , intracoronary @entity452 infusion at rates of 25 and 50 micrograms/min increased peak +dP/dt by 131 +/- 24 and 168 +/- 22%, respectively (P < 0.0001). Vagal stimulation (2.5 Hz) attenuated the responses to @entity452 (25 and 50 micrograms/min) by 23 +/- 4 and 21 +/- 4%, respectively (P < 0.001). @entity7293 reduced (by 44-62%; P < 0.001) and @entity534 restored vagal inhibition of the @entity452 -stimulated inotropic response. In a second group of nine @entity235 , @entity452 was administered systemically to assure a constant concentration in the coronary circulation. Vagal stimulation (2.5 Hz) attenuated the @entity452 -stimulated inotropic response (2.5 and 5.0 micrograms/kg per min) by 40 +/- 12% and 57 +/- 8%, respectively (P < 0.004). As with intracoronary @entity452 , @entity7293 diminished and @entity534 restored vagal inhibition of the inotropic response to @entity452 . Intracoronary infusion of @entity3897 (12 micrograms/min) abolished the vagal inhibitory effect, and intracoronary infusion of @entity8263 (1 and 10 mM) caused a dose-dependent attenuation of the @entity452 -stimulated increase in +dP/dt. These data suggest that NO mediates, at least in part, vagal inhibition of the inotropic response to beta-adrenergic stimulation by @entity452 , and thus may play a role in normal physiologic regulation of myocardial autonomic responses.
