TY - JOUR
T1 - Carvedilol's actions are largely mediated by endogenous nitric oxide
AU - Patarrão, Rita Susana Franco das Neves
AU - Afonso, Ricardo Alexandre da Silva Santos
AU - Carmo, Miguel Adriano Bento Mota
AU - Macedo, Maria Paula Borges de Lemos
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 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.
AB - 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.
KW - Hypertension
KW - Nitric oxide (NO)
KW - Arterial blood pressure
KW - Carvedilol
KW - Heart failure
M3 - Article
C2 - 17190240
VL - 25
SP - 911
EP - 917
JO - Revista Portuguesa de Cardiologia
JF - Revista Portuguesa de Cardiologia
SN - 0870-2551
IS - 10
ER -