Role of nitric oxide in parasympathetic modulation of beta-adrenergic myocardial contractility in normal dogs
| Autor: | Joseph Loscalzo, Joshua M. Hare, John F. Keaney, Wilson S. Colucci, Thomas W. Smith, J.-L. Balligand |
|---|---|
| Přispěvatelé: | UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique |
| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Inotrope
medicine.medical_specialty Arginine - analogs & derivatives pharmacology medicine.medical_treatment Stimulation Muscarinic Antagonists Arginine Nitric Oxide Amino Acid Oxidoreductases - antagonists & inhibitors Cyclic AMP - pharmacology Contractility Dogs Vagus Nerve - physiology Heart Rate Dobutamine Internal medicine Dobutamine - pharmacology Receptors Adrenergic beta Cyclic AMP medicine Animals Myocardial Contraction - drug effects physiology omega-N-Methylarginine business.industry Receptors Adrenergic beta - physiology Heart - innervation Heart Vagus Nerve General Medicine Myocardial Contraction Electric Stimulation Vagus nerve Atropine Endocrinology Nitric Oxide - antagonists & inhibitors metabolism Omega-N-Methylarginine Amino Acid Oxidoreductases Nitric Oxide Synthase business Vagus nerve stimulation Research Article medicine.drug |
| Zdroj: | The Journal of clinical investigation, Vol. 95, no. 1, p. 360-6 (1995) |
| Popis: | In vitro studies indicate that muscarinic cholinergic inhibition of beta-adrenergic cardiac responses may be modulated in part by nitric oxide (NO). To evaluate the role of NO in parasympathetic inhibition of the beta-adrenergic contractile response in vivo, we assessed the inotropic response to dobutamine before and during bilateral vagus nerve stimulation in closed-chest dogs. Dobutamine administration and vagal stimulation were repeated during intracoronary infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 10 mumol/min) and again following infusion of L-arginine (100 mg/kg). In eight dogs, intracoronary dobutamine 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 dobutamine (25 and 50 micrograms/min) by 23 +/- 4 and 21 +/- 4%, respectively (P < 0.001). L-NMMA reduced (by 44-62%; P < 0.001) and L-arginine restored vagal inhibition of the dobutamine-stimulated inotropic response. In a second group of nine dogs, dobutamine was administered systemically to assure a constant concentration in the coronary circulation. Vagal stimulation (2.5 Hz) attenuated the dobutamine-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 dobutamine, L-NMMA diminished and L-arginine restored vagal inhibition of the inotropic response to dobutamine. Intracoronary infusion of atropine (12 micrograms/min) abolished the vagal inhibitory effect, and intracoronary infusion of 8-bromo-cyclic GMP (1 and 10 mM) caused a dose-dependent attenuation of the dobutamine-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 dobutamine, and thus may play a role in normal physiologic regulation of myocardial autonomic responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|