Limits...
Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction.

Murdoch CE, Alom-Ruiz SP, Wang M, Zhang M, Walker S, Yu B, Brewer A, Shah AM - Basic Res. Cardiol. (2011)

Bottom Line: Basal NADPH oxidase activity, endothelial function and blood pressure were unaltered in Tg compared to wild-type littermates.Angiotensin II caused a greater increase in ROS production in Tg compared to wild-type aorta and attenuated acetylcholine-induced vasorelaxation.Both low and high dose chronic angiotensin II infusion increased telemetric ambulatory blood pressure more in Tg compared to wild-type, but with different patterns of BP change and aortic remodeling depending upon the dose of angiotensin II dose.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre, London, UK.

ABSTRACT
NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial Nox2 in vivo. To address this question, we generated transgenic mice with endothelial-specific overexpression of Nox2 (Tg) and studied the effects on endothelial function and blood pressure. Tg had an about twofold increase in endothelial Nox2 levels which was accompanied by an increase in p22phox levels but no change in levels of other Nox isoforms or endothelial nitric oxide synthase (eNOS). Basal NADPH oxidase activity, endothelial function and blood pressure were unaltered in Tg compared to wild-type littermates. Angiotensin II caused a greater increase in ROS production in Tg compared to wild-type aorta and attenuated acetylcholine-induced vasorelaxation. Both low and high dose chronic angiotensin II infusion increased telemetric ambulatory blood pressure more in Tg compared to wild-type, but with different patterns of BP change and aortic remodeling depending upon the dose of angiotensin II dose. These results indicate that an increase in endothelial Nox2 levels contributes to angiotensin II-induced endothelial dysfunction, vascular remodeling and hypertension.

Show MeSH

Related in: MedlinePlus

Effect of chronic angiotensin II treatment on blood pressure in Tg and WT mice. Ambulatory blood pressure was measured in WT and Tg mice before and after implantation of osmotic pumps delivering either a saline, b low dose AngII (0.3 mg/kg/day) or c high dose AngII (1.1 mg/kg/day). Systolic, diastolic and mean blood pressure and heart rate were averaged over 24 h periods. n = 6, *P < 0.05 for a significant interaction by two-way ANOVA
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3105229&req=5

Fig5: Effect of chronic angiotensin II treatment on blood pressure in Tg and WT mice. Ambulatory blood pressure was measured in WT and Tg mice before and after implantation of osmotic pumps delivering either a saline, b low dose AngII (0.3 mg/kg/day) or c high dose AngII (1.1 mg/kg/day). Systolic, diastolic and mean blood pressure and heart rate were averaged over 24 h periods. n = 6, *P < 0.05 for a significant interaction by two-way ANOVA

Mentions: Ambulatory blood pressure was measured in Tg and wild-type mice by telemetry. There was no difference in systolic, diastolic or mean blood pressure between groups at baseline (Fig. 5a). To assess the response to angiotensin II, mice were implanted with osmotic minipumps infusing either angiotensin II or saline over a 2-week period. Saline infusion did not cause any changes in blood pressure (Fig. 5a). A low dose of angiotensin II (i.e. 0.3 mg/kg/day), which normally has no effect on blood pressure in wild-type mice caused significant increases in systolic, diastolic and mean blood pressure in Tg mice but no change in wild-type littermates (Fig. 4b). We also tested the effects of a high dose of angiotensin II (1.1 mg/kg/day). This resulted in similar rises in systolic and mean blood pressure in Tg and wild-type mice but diastolic blood pressure increased to a significantly greater extent in Tg compared with wild-type (Fig. 5c).Heart rates (Fig. 5, lower panels) and activity level (not shown) were similar in the Tg and wild-type groups).Fig. 5


Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction.

Murdoch CE, Alom-Ruiz SP, Wang M, Zhang M, Walker S, Yu B, Brewer A, Shah AM - Basic Res. Cardiol. (2011)

Effect of chronic angiotensin II treatment on blood pressure in Tg and WT mice. Ambulatory blood pressure was measured in WT and Tg mice before and after implantation of osmotic pumps delivering either a saline, b low dose AngII (0.3 mg/kg/day) or c high dose AngII (1.1 mg/kg/day). Systolic, diastolic and mean blood pressure and heart rate were averaged over 24 h periods. n = 6, *P < 0.05 for a significant interaction by two-way ANOVA
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105229&req=5

Fig5: Effect of chronic angiotensin II treatment on blood pressure in Tg and WT mice. Ambulatory blood pressure was measured in WT and Tg mice before and after implantation of osmotic pumps delivering either a saline, b low dose AngII (0.3 mg/kg/day) or c high dose AngII (1.1 mg/kg/day). Systolic, diastolic and mean blood pressure and heart rate were averaged over 24 h periods. n = 6, *P < 0.05 for a significant interaction by two-way ANOVA
Mentions: Ambulatory blood pressure was measured in Tg and wild-type mice by telemetry. There was no difference in systolic, diastolic or mean blood pressure between groups at baseline (Fig. 5a). To assess the response to angiotensin II, mice were implanted with osmotic minipumps infusing either angiotensin II or saline over a 2-week period. Saline infusion did not cause any changes in blood pressure (Fig. 5a). A low dose of angiotensin II (i.e. 0.3 mg/kg/day), which normally has no effect on blood pressure in wild-type mice caused significant increases in systolic, diastolic and mean blood pressure in Tg mice but no change in wild-type littermates (Fig. 4b). We also tested the effects of a high dose of angiotensin II (1.1 mg/kg/day). This resulted in similar rises in systolic and mean blood pressure in Tg and wild-type mice but diastolic blood pressure increased to a significantly greater extent in Tg compared with wild-type (Fig. 5c).Heart rates (Fig. 5, lower panels) and activity level (not shown) were similar in the Tg and wild-type groups).Fig. 5

Bottom Line: Basal NADPH oxidase activity, endothelial function and blood pressure were unaltered in Tg compared to wild-type littermates.Angiotensin II caused a greater increase in ROS production in Tg compared to wild-type aorta and attenuated acetylcholine-induced vasorelaxation.Both low and high dose chronic angiotensin II infusion increased telemetric ambulatory blood pressure more in Tg compared to wild-type, but with different patterns of BP change and aortic remodeling depending upon the dose of angiotensin II dose.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre, London, UK.

ABSTRACT
NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial Nox2 in vivo. To address this question, we generated transgenic mice with endothelial-specific overexpression of Nox2 (Tg) and studied the effects on endothelial function and blood pressure. Tg had an about twofold increase in endothelial Nox2 levels which was accompanied by an increase in p22phox levels but no change in levels of other Nox isoforms or endothelial nitric oxide synthase (eNOS). Basal NADPH oxidase activity, endothelial function and blood pressure were unaltered in Tg compared to wild-type littermates. Angiotensin II caused a greater increase in ROS production in Tg compared to wild-type aorta and attenuated acetylcholine-induced vasorelaxation. Both low and high dose chronic angiotensin II infusion increased telemetric ambulatory blood pressure more in Tg compared to wild-type, but with different patterns of BP change and aortic remodeling depending upon the dose of angiotensin II dose. These results indicate that an increase in endothelial Nox2 levels contributes to angiotensin II-induced endothelial dysfunction, vascular remodeling and hypertension.

Show MeSH
Related in: MedlinePlus