8 Citations (Scopus)

Abstract

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.
Original languageUnknown
Pages (from-to)911-7
JournalRevista Portuguesa de Cardiologia
Volume25
Issue number10
Publication statusPublished - 1 Jan 2006

Cite this

@article{1be421542dda4561873558f3d0cbfaca,
title = "Carvedilol's actions are largely mediated by endogenous nitric oxide",
abstract = "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.",
keywords = "Hypertension, Nitric oxide (NO), Arterial blood pressure, Carvedilol, Heart failure",
author = "Patarr{\~a}o, {Rita Susana Franco das Neves} and Afonso, {Ricardo Alexandre da Silva Santos} and Carmo, {Miguel Adriano Bento Mota} and Macedo, {Maria Paula Borges de Lemos}",
year = "2006",
month = "1",
day = "1",
language = "Unknown",
volume = "25",
pages = "911--7",
journal = "Revista Portuguesa de Cardiologia",
issn = "0870-2551",
publisher = "Sociedade Portuguesa de Cardiologia",
number = "10",

}

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

VL - 25

SP - 911

EP - 917

JO - Revista Portuguesa de Cardiologia

JF - Revista Portuguesa de Cardiologia

SN - 0870-2551

IS - 10

ER -