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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 the level of the AT1-R in the PVN and ANGII in the plasma in 2K1C rats.2K1C rats had higher protein expression of AT1-R in the PVN and higher level of ANGII in the plasma compared with SHAM rats. ExT significantly decreased AT1-R expression in the PVN and ANGII in the plasma compared with 2K1C + Sed rats. AT1-R: angiotensin II type1 receptor; ANG II: angiotensin II; 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. (a) Levels of ANGII in the plasma in different groups. (b) Representative immunoblot of AT1-R. (c) Densitometric analysis of protein expression of AT1-R.
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f5: Effects of exercise training on the level of the AT1-R in the PVN and ANGII in the plasma in 2K1C rats.2K1C rats had higher protein expression of AT1-R in the PVN and higher level of ANGII in the plasma compared with SHAM rats. ExT significantly decreased AT1-R expression in the PVN and ANGII in the plasma compared with 2K1C + Sed rats. AT1-R: angiotensin II type1 receptor; ANG II: angiotensin II; 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. (a) Levels of ANGII in the plasma in different groups. (b) Representative immunoblot of AT1-R. (c) Densitometric analysis of protein expression of AT1-R.

Mentions: Immunofluorescence revealed that renovascular hypertensive rats had a significant increase of ACE and AT1-R expression in the PVN compared with SHAM rats. ExT decreased ACE- and AT1-R-positive neurons in the PVN and decreased plasma levels of ANG II in renovascular hypertensive rats (Figs 3, 4 and 5a). ELISA analysis revealed that 2K1C rats had a higher level of ANG II in the plasma compared with SHAM rats (Fig. 5a). Western blotting showed that renovascular hypertension up-regulated the expression ofAT1-R compared with that in SHAM rats. ExT also attenuated the expression of AT1-R (Fig. 5b and 5c), suggesting that ExT attenuates RAS activation in renovascular hypertension.


Exercise training attenuates renovascular hypertension partly via RAS- ROS- glutamate pathway in the hypothalamic paraventricular nucleus
Effects of exercise training on the level of the AT1-R in the PVN and ANGII in the plasma in 2K1C rats.2K1C rats had higher protein expression of AT1-R in the PVN and higher level of ANGII in the plasma compared with SHAM rats. ExT significantly decreased AT1-R expression in the PVN and ANGII in the plasma compared with 2K1C + Sed rats. AT1-R: angiotensin II type1 receptor; ANG II: angiotensin II; 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. (a) Levels of ANGII in the plasma in different groups. (b) Representative immunoblot of AT1-R. (c) Densitometric analysis of protein expression of AT1-R.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5121597&req=5

f5: Effects of exercise training on the level of the AT1-R in the PVN and ANGII in the plasma in 2K1C rats.2K1C rats had higher protein expression of AT1-R in the PVN and higher level of ANGII in the plasma compared with SHAM rats. ExT significantly decreased AT1-R expression in the PVN and ANGII in the plasma compared with 2K1C + Sed rats. AT1-R: angiotensin II type1 receptor; ANG II: angiotensin II; 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. (a) Levels of ANGII in the plasma in different groups. (b) Representative immunoblot of AT1-R. (c) Densitometric analysis of protein expression of AT1-R.
Mentions: Immunofluorescence revealed that renovascular hypertensive rats had a significant increase of ACE and AT1-R expression in the PVN compared with SHAM rats. ExT decreased ACE- and AT1-R-positive neurons in the PVN and decreased plasma levels of ANG II in renovascular hypertensive rats (Figs 3, 4 and 5a). ELISA analysis revealed that 2K1C rats had a higher level of ANG II in the plasma compared with SHAM rats (Fig. 5a). Western blotting showed that renovascular hypertension up-regulated the expression ofAT1-R compared with that in SHAM rats. ExT also attenuated the expression of AT1-R (Fig. 5b and 5c), suggesting that ExT attenuates RAS activation 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.