Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 419-425 |
| Number of pages | 7 |
| Journal | American Journal Of Hypertension |
| Volume | 19 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jan 2006 |
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Carvedilol action is dependent on endogenous production of nitric oxide. / Patarrão, Rita Susana Franco das Neves; Afonso, Ricardo Alexandre da Silva Santos; Carmo, Miguel Adriano Bento Mota; Macedo, Maria Paula Borges de Lemos.
In: American Journal Of Hypertension, Vol. 19, No. 4, 01.2006, p. 419-425.Research output: Contribution to journal › Article
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 -