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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 eight-week exercise training or PVN microinjection of MK801 or Los on RSNA in 2K1C rats and SHAM rats.RSNA was increased in 2K1C rats compared with SHAM rats. ExT attenuated RSNA compared with 2K1C + Sed rats. Treatment with PVN microinjection of MK801 or Los attenuated RSNA of 2K1C rats. PVN microinjection of Los exhibited lower RSNA (% of max) compared with PVN microinjection of MK801 in 2K1C rats. RSNA: renal sympathetic nerve activity; PVN: hypothalamic paraventricular nucleus; 2K1C: two-kidney, one-clip; ExT: exercise training; Sed: sedentary; MK801: dizocilpine; Los: losartan. Values are expressed as means ± SE. *P < 0.05 vs SHAM groups (SHAM + Sed or SHAM + ExT); †P < 0.05 vs 2K1C groups (2K1C + ExT or 2K1C + Sed); #P < 0.05 vs 2K1C+PVN microinjection of MK801 (2K1C + ExT+ PVN microinjection of MK801 or 2K1C + Sed + PVN microinjection of MK801.
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f2: Effects of eight-week exercise training or PVN microinjection of MK801 or Los on RSNA in 2K1C rats and SHAM rats.RSNA was increased in 2K1C rats compared with SHAM rats. ExT attenuated RSNA compared with 2K1C + Sed rats. Treatment with PVN microinjection of MK801 or Los attenuated RSNA of 2K1C rats. PVN microinjection of Los exhibited lower RSNA (% of max) compared with PVN microinjection of MK801 in 2K1C rats. RSNA: renal sympathetic nerve activity; PVN: hypothalamic paraventricular nucleus; 2K1C: two-kidney, one-clip; ExT: exercise training; Sed: sedentary; MK801: dizocilpine; Los: losartan. Values are expressed as means ± SE. *P < 0.05 vs SHAM groups (SHAM + Sed or SHAM + ExT); †P < 0.05 vs 2K1C groups (2K1C + ExT or 2K1C + Sed); #P < 0.05 vs 2K1C+PVN microinjection of MK801 (2K1C + ExT+ PVN microinjection of MK801 or 2K1C + Sed + PVN microinjection of MK801.

Mentions: RSNA was increased in 2K1C rats compared with that in SHAM rats. ExT treatment with PVNmicroinjection of MK801 or Los attenuated RSNA of 2K1C rats. PVN microinjection of Los exhibited lower RSNA (%of max) compared with PVN microinjection of MK801 in 2K1C rats (Fig. 2). These results suggest that ExT attenuates RSNA, in part, through decrease of glutamate in renovascular hypertensive rats.


Exercise training attenuates renovascular hypertension partly via RAS- ROS- glutamate pathway in the hypothalamic paraventricular nucleus
Effects of eight-week exercise training or PVN microinjection of MK801 or Los on RSNA in 2K1C rats and SHAM rats.RSNA was increased in 2K1C rats compared with SHAM rats. ExT attenuated RSNA compared with 2K1C + Sed rats. Treatment with PVN microinjection of MK801 or Los attenuated RSNA of 2K1C rats. PVN microinjection of Los exhibited lower RSNA (% of max) compared with PVN microinjection of MK801 in 2K1C rats. RSNA: renal sympathetic nerve activity; PVN: hypothalamic paraventricular nucleus; 2K1C: two-kidney, one-clip; ExT: exercise training; Sed: sedentary; MK801: dizocilpine; Los: losartan. Values are expressed as means ± SE. *P < 0.05 vs SHAM groups (SHAM + Sed or SHAM + ExT); †P < 0.05 vs 2K1C groups (2K1C + ExT or 2K1C + Sed); #P < 0.05 vs 2K1C+PVN microinjection of MK801 (2K1C + ExT+ PVN microinjection of MK801 or 2K1C + Sed + PVN microinjection of MK801.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f2: Effects of eight-week exercise training or PVN microinjection of MK801 or Los on RSNA in 2K1C rats and SHAM rats.RSNA was increased in 2K1C rats compared with SHAM rats. ExT attenuated RSNA compared with 2K1C + Sed rats. Treatment with PVN microinjection of MK801 or Los attenuated RSNA of 2K1C rats. PVN microinjection of Los exhibited lower RSNA (% of max) compared with PVN microinjection of MK801 in 2K1C rats. RSNA: renal sympathetic nerve activity; PVN: hypothalamic paraventricular nucleus; 2K1C: two-kidney, one-clip; ExT: exercise training; Sed: sedentary; MK801: dizocilpine; Los: losartan. Values are expressed as means ± SE. *P < 0.05 vs SHAM groups (SHAM + Sed or SHAM + ExT); †P < 0.05 vs 2K1C groups (2K1C + ExT or 2K1C + Sed); #P < 0.05 vs 2K1C+PVN microinjection of MK801 (2K1C + ExT+ PVN microinjection of MK801 or 2K1C + Sed + PVN microinjection of MK801.
Mentions: RSNA was increased in 2K1C rats compared with that in SHAM rats. ExT treatment with PVNmicroinjection of MK801 or Los attenuated RSNA of 2K1C rats. PVN microinjection of Los exhibited lower RSNA (%of max) compared with PVN microinjection of MK801 in 2K1C rats (Fig. 2). These results suggest that ExT attenuates RSNA, in part, through decrease of glutamate in renovascular hypertensive rats.

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.