29 Citations (Scopus)

Abstract

Background: Carvedilol is known to be an adrenoreceptor blocker and free radical scavenger, used in hypertension and cardiac failure. However, its therapeutic actions cannot be fully explained by these mechanisms. In these studies, we tested the hypothesis that carvedilol action is associated with the synthesis/release of nitric oxide (NO). Methods: Male Wistar rats (n = 22), 9 weeks old, were anesthetized with an intraperitoneal injection of sodium pentobarbital. Mean arterial pressure and arterial NO levels were monitored throughout the experiments. Carvedilol (1 mg/kg, intravenously [iv]) effects were evaluated before and after NO synthase (NOS) inhibitor N(omega)-nitro-Larginine methyl ester (L-NAME, 5 mg/kg, iv). Results: Carvedilol induced a significant decrease in basal arterial pressure (from 126.6 +/- 4.3 mm Hg to 75.9 +/- 3.0 mm Hg, P < .001) and significant increase in NO levels (from 17.9 +/- 1.7 mu mol/L to 32.2 +/- 2.5 mu mol/L, P < .001). After administration of L-NAME the arterial pressure increased (129.9 +/- 5.0 mm Hg, P < .001) with concomitant decrease in NO levels (13.4 +/- 1.6 mu mol/L, P < .01). The second carvedilol administration (post-L-NAME) did not affect either arterial pressure (108.3 +/- 8.0 mm Hg) or NO levels (22.1 +/- 1.3 mu mol/L). Conclusions: Our results suggest that the carvedilol-induced decrease of blood pressure is associated with an increase of plasma NO levels. Furthermore, NOS inhibition results in impairment of carvedilol hemodynamic effects and plasma NO levels. Therefore, these results are consistent with the hypothesis that the hemodynamic effect of carvedilol is in part dependent on endogenous NO production.
Original languageEnglish
Pages (from-to)419-425
Number of pages7
JournalAmerican Journal Of Hypertension
Volume19
Issue number4
DOIs
Publication statusPublished - Jan 2006

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Nitric Oxide
NG-Nitroarginine Methyl Ester
Arterial Pressure
Nitric Oxide Synthase
Hemodynamics
Free Radical Scavengers
carvedilol
Pentobarbital
Intraperitoneal Injections
Wistar Rats
Esters
Heart Failure
Blood Pressure
Hypertension

Cite this

@article{5911de2ce202455b98db65e8481feba2,
title = "Carvedilol action is dependent on endogenous production of nitric oxide",
abstract = "Background: Carvedilol is known to be an adrenoreceptor blocker and free radical scavenger, used in hypertension and cardiac failure. However, its therapeutic actions cannot be fully explained by these mechanisms. In these studies, we tested the hypothesis that carvedilol action is associated with the synthesis/release of nitric oxide (NO). Methods: Male Wistar rats (n = 22), 9 weeks old, were anesthetized with an intraperitoneal injection of sodium pentobarbital. Mean arterial pressure and arterial NO levels were monitored throughout the experiments. Carvedilol (1 mg/kg, intravenously [iv]) effects were evaluated before and after NO synthase (NOS) inhibitor N(omega)-nitro-Larginine methyl ester (L-NAME, 5 mg/kg, iv). Results: Carvedilol induced a significant decrease in basal arterial pressure (from 126.6 +/- 4.3 mm Hg to 75.9 +/- 3.0 mm Hg, P < .001) and significant increase in NO levels (from 17.9 +/- 1.7 mu mol/L to 32.2 +/- 2.5 mu mol/L, P < .001). After administration of L-NAME the arterial pressure increased (129.9 +/- 5.0 mm Hg, P < .001) with concomitant decrease in NO levels (13.4 +/- 1.6 mu mol/L, P < .01). The second carvedilol administration (post-L-NAME) did not affect either arterial pressure (108.3 +/- 8.0 mm Hg) or NO levels (22.1 +/- 1.3 mu mol/L). Conclusions: Our results suggest that the carvedilol-induced decrease of blood pressure is associated with an increase of plasma NO levels. Furthermore, NOS inhibition results in impairment of carvedilol hemodynamic effects and plasma NO levels. Therefore, these results are consistent with the hypothesis that the hemodynamic effect of carvedilol is in part dependent on endogenous NO production.",
keywords = "NO, nitric oxide, carvedilol, INHIBITION, ANTIHYPERTENSIVE AGENT, L-ARGININE, PATHWAY, CHEMI-LUMINESCENCE, ENDOTHELIAL-CELLS, NITRATE, blood pressure, HEART-FAILURE, SHEAR-INDUCED MODULATION",
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",
doi = "10.1016/j.amjhyper.2005.11.011",
language = "English",
volume = "19",
pages = "419--425",
journal = "American Journal Of Hypertension",
issn = "0895-7061",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Carvedilol action is dependent on endogenous production of 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

Y1 - 2006/1

N2 - Background: Carvedilol is known to be an adrenoreceptor blocker and free radical scavenger, used in hypertension and cardiac failure. However, its therapeutic actions cannot be fully explained by these mechanisms. In these studies, we tested the hypothesis that carvedilol action is associated with the synthesis/release of nitric oxide (NO). Methods: Male Wistar rats (n = 22), 9 weeks old, were anesthetized with an intraperitoneal injection of sodium pentobarbital. Mean arterial pressure and arterial NO levels were monitored throughout the experiments. Carvedilol (1 mg/kg, intravenously [iv]) effects were evaluated before and after NO synthase (NOS) inhibitor N(omega)-nitro-Larginine methyl ester (L-NAME, 5 mg/kg, iv). Results: Carvedilol induced a significant decrease in basal arterial pressure (from 126.6 +/- 4.3 mm Hg to 75.9 +/- 3.0 mm Hg, P < .001) and significant increase in NO levels (from 17.9 +/- 1.7 mu mol/L to 32.2 +/- 2.5 mu mol/L, P < .001). After administration of L-NAME the arterial pressure increased (129.9 +/- 5.0 mm Hg, P < .001) with concomitant decrease in NO levels (13.4 +/- 1.6 mu mol/L, P < .01). The second carvedilol administration (post-L-NAME) did not affect either arterial pressure (108.3 +/- 8.0 mm Hg) or NO levels (22.1 +/- 1.3 mu mol/L). Conclusions: Our results suggest that the carvedilol-induced decrease of blood pressure is associated with an increase of plasma NO levels. Furthermore, NOS inhibition results in impairment of carvedilol hemodynamic effects and plasma NO levels. Therefore, these results are consistent with the hypothesis that the hemodynamic effect of carvedilol is in part dependent on endogenous NO production.

AB - Background: Carvedilol is known to be an adrenoreceptor blocker and free radical scavenger, used in hypertension and cardiac failure. However, its therapeutic actions cannot be fully explained by these mechanisms. In these studies, we tested the hypothesis that carvedilol action is associated with the synthesis/release of nitric oxide (NO). Methods: Male Wistar rats (n = 22), 9 weeks old, were anesthetized with an intraperitoneal injection of sodium pentobarbital. Mean arterial pressure and arterial NO levels were monitored throughout the experiments. Carvedilol (1 mg/kg, intravenously [iv]) effects were evaluated before and after NO synthase (NOS) inhibitor N(omega)-nitro-Larginine methyl ester (L-NAME, 5 mg/kg, iv). Results: Carvedilol induced a significant decrease in basal arterial pressure (from 126.6 +/- 4.3 mm Hg to 75.9 +/- 3.0 mm Hg, P < .001) and significant increase in NO levels (from 17.9 +/- 1.7 mu mol/L to 32.2 +/- 2.5 mu mol/L, P < .001). After administration of L-NAME the arterial pressure increased (129.9 +/- 5.0 mm Hg, P < .001) with concomitant decrease in NO levels (13.4 +/- 1.6 mu mol/L, P < .01). The second carvedilol administration (post-L-NAME) did not affect either arterial pressure (108.3 +/- 8.0 mm Hg) or NO levels (22.1 +/- 1.3 mu mol/L). Conclusions: Our results suggest that the carvedilol-induced decrease of blood pressure is associated with an increase of plasma NO levels. Furthermore, NOS inhibition results in impairment of carvedilol hemodynamic effects and plasma NO levels. Therefore, these results are consistent with the hypothesis that the hemodynamic effect of carvedilol is in part dependent on endogenous NO production.

KW - NO

KW - nitric oxide

KW - carvedilol

KW - INHIBITION

KW - ANTIHYPERTENSIVE AGENT

KW - L-ARGININE

KW - PATHWAY

KW - CHEMI-LUMINESCENCE

KW - ENDOTHELIAL-CELLS

KW - NITRATE

KW - blood pressure

KW - HEART-FAILURE

KW - SHEAR-INDUCED MODULATION

U2 - 10.1016/j.amjhyper.2005.11.011

DO - 10.1016/j.amjhyper.2005.11.011

M3 - Article

VL - 19

SP - 419

EP - 425

JO - American Journal Of Hypertension

JF - American Journal Of Hypertension

SN - 0895-7061

IS - 4

ER -