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Exercise training attenuates renovascular hypertension partly via RAS- ROS- glutamate pathway in the hypothalamic paraventricular nucleus

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ABSTRACT

Exercise training (ExT) has been reported to benefit hypertension; however, the exact mechanisms involved are unclear. We hypothesized that ExT attenuates hypertension, in part, through the renin-angiotensin system (RAS), reactive oxygen species (ROS), and glutamate in the paraventricular nucleus (PVN). Two-kidney, one-clip (2K1C) renovascular hypertensive rats were assigned to sedentary (Sed) or treadmill running groups for eight weeks. Dizocilpine (MK801), a glutamate receptor blocker, or losartan (Los), an angiotensin II type1 receptor (AT1-R) blocker, were microinjected into the PVN at the end of the experiment. We found that 2K1C rats had higher mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These rats also had excessive oxidative stress and overactivated RAS in PVN. Eight weeks of ExT significantly decreased MAP and RSNA in 2K1C hypertensive rats. ExT inhibited angiotensin-converting enzyme (ACE), AT1-R, and glutamate in the PVN, and angiotensin II (ANG II) in the plasma. Moreover, ExT attenuated ROS by augmenting copper/zinc superoxide dismutase (Cu/Zn-SOD) and decreasing p47phox and gp91phox in the PVN. MK801or Los significantly decreased blood pressure in rats. Together, these findings suggest that the beneficial effects of ExT on renovascular hypertension may be, in part, through the RAS-ROS-glutamate pathway in the PVN.

No MeSH data available.


Effects of exercise training on gp91phox and p47phox in the PVN in 2K1C rats by immunofluorescence staining.2K1C rats had higher levels of gp91phox and p47phox compared with SHAM rats. ExT decreased gp91phox and p47phox expression in the PVN compared with 2K1C + Sed rats. (a) A representative immunofluorescence staining of gp91phox. (b) A representative immunofluorescence staining of p47phox. (c) Densitometric analysis of immunofluorescent intensity of gp91phox in the PVN in different groups. (d) Densitometric analysis of immunofluorescent intensity of p47phox in the PVN in different groups. PVN: hypothalamic paraventricular nucleus; 2K1C: two-kidney, one-clip; ExT: exercise training; Sed: sedentary. Values are expressed as means ± SE. *P < 0.05 vs SHAM groups (SHAM + Sed or SHAM + ExT); †P < 0.05 2K1C + ExT vs 2K1C + Sed.
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f7: Effects of exercise training on gp91phox and p47phox in the PVN in 2K1C rats by immunofluorescence staining.2K1C rats had higher levels of gp91phox and p47phox compared with SHAM rats. ExT decreased gp91phox and p47phox expression in the PVN compared with 2K1C + Sed rats. (a) A representative immunofluorescence staining of gp91phox. (b) A representative immunofluorescence staining of p47phox. (c) Densitometric analysis of immunofluorescent intensity of gp91phox in the PVN in different groups. (d) Densitometric analysis of immunofluorescent intensity of p47phox in the PVN in different groups. PVN: hypothalamic paraventricular nucleus; 2K1C: two-kidney, one-clip; ExT: exercise training; Sed: sedentary. Values are expressed as means ± SE. *P < 0.05 vs SHAM groups (SHAM + Sed or SHAM + ExT); †P < 0.05 2K1C + ExT vs 2K1C + Sed.

Mentions: Immunofluorescence revealed that renovascular hypertensive rats had significant increase in the expression of p47phox, gp91phox, and DHE in the PVN compared with SHAM rats. ExT decreasedp47phox, gp91phox, and DHE-positive neurons in hypertensive rats (Fig. 6 and 7). Western blotting indicated that 2K1C hypertensive rats had lower levels of Cu/Zn-SOD and higher levels of p47phox compared with SHAM rats. ExT enhanced the expression of Cu/Zn-SOD and decreased the expression of p47phox (Fig. 8). This suggests that ExT attenuates oxidative stress in renovascular hypertension.


Exercise training attenuates renovascular hypertension partly via RAS- ROS- glutamate pathway in the hypothalamic paraventricular nucleus
Effects of exercise training on gp91phox and p47phox in the PVN in 2K1C rats by immunofluorescence staining.2K1C rats had higher levels of gp91phox and p47phox compared with SHAM rats. ExT decreased gp91phox and p47phox expression in the PVN compared with 2K1C + Sed rats. (a) A representative immunofluorescence staining of gp91phox. (b) A representative immunofluorescence staining of p47phox. (c) Densitometric analysis of immunofluorescent intensity of gp91phox in the PVN in different groups. (d) Densitometric analysis of immunofluorescent intensity of p47phox in the PVN in different groups. PVN: hypothalamic paraventricular nucleus; 2K1C: two-kidney, one-clip; ExT: exercise training; Sed: sedentary. Values are expressed as means ± SE. *P < 0.05 vs SHAM groups (SHAM + Sed or SHAM + ExT); †P < 0.05 2K1C + ExT vs 2K1C + Sed.
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f7: Effects of exercise training on gp91phox and p47phox in the PVN in 2K1C rats by immunofluorescence staining.2K1C rats had higher levels of gp91phox and p47phox compared with SHAM rats. ExT decreased gp91phox and p47phox expression in the PVN compared with 2K1C + Sed rats. (a) A representative immunofluorescence staining of gp91phox. (b) A representative immunofluorescence staining of p47phox. (c) Densitometric analysis of immunofluorescent intensity of gp91phox in the PVN in different groups. (d) Densitometric analysis of immunofluorescent intensity of p47phox in the PVN in different groups. PVN: hypothalamic paraventricular nucleus; 2K1C: two-kidney, one-clip; ExT: exercise training; Sed: sedentary. Values are expressed as means ± SE. *P < 0.05 vs SHAM groups (SHAM + Sed or SHAM + ExT); †P < 0.05 2K1C + ExT vs 2K1C + Sed.
Mentions: Immunofluorescence revealed that renovascular hypertensive rats had significant increase in the expression of p47phox, gp91phox, and DHE in the PVN compared with SHAM rats. ExT decreasedp47phox, gp91phox, and DHE-positive neurons in hypertensive rats (Fig. 6 and 7). Western blotting indicated that 2K1C hypertensive rats had lower levels of Cu/Zn-SOD and higher levels of p47phox compared with SHAM rats. ExT enhanced the expression of Cu/Zn-SOD and decreased the expression of p47phox (Fig. 8). This suggests that ExT attenuates oxidative stress in renovascular hypertension.

View Article: PubMed Central - PubMed

ABSTRACT

Exercise training (ExT) has been reported to benefit hypertension; however, the exact mechanisms involved are unclear. We hypothesized that ExT attenuates hypertension, in part, through the renin-angiotensin system (RAS), reactive oxygen species (ROS), and glutamate in the paraventricular nucleus (PVN). Two-kidney, one-clip (2K1C) renovascular hypertensive rats were assigned to sedentary (Sed) or treadmill running groups for eight weeks. Dizocilpine (MK801), a glutamate receptor blocker, or losartan (Los), an angiotensin II type1 receptor (AT1-R) blocker, were microinjected into the PVN at the end of the experiment. We found that 2K1C rats had higher mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These rats also had excessive oxidative stress and overactivated RAS in PVN. Eight weeks of ExT significantly decreased MAP and RSNA in 2K1C hypertensive rats. ExT inhibited angiotensin-converting enzyme (ACE), AT1-R, and glutamate in the PVN, and angiotensin II (ANG II) in the plasma. Moreover, ExT attenuated ROS by augmenting copper/zinc superoxide dismutase (Cu/Zn-SOD) and decreasing p47phox and gp91phox in the PVN. MK801or Los significantly decreased blood pressure in rats. Together, these findings suggest that the beneficial effects of ExT on renovascular hypertension may be, in part, through the RAS-ROS-glutamate pathway in the PVN.

No MeSH data available.