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Brain endogenous angiotensin II receptor type 2 (AT2-R) protects against DOCA/salt-induced hypertension in female rats.

Dai SY, Peng W, Zhang YP, Li JD, Shen Y, Sun XF - J Neuroinflammation (2015)

Bottom Line: Icv infusions of the AT2-R antagonist significantly augmented DOCA/salt pressor effects in females.However, this same treatment had no enhanced effect on DOCA/salt-induced increase in the BP in males.The protective effect of AT2-R in females involves regulating the expression of brain renin-angiotensin system components and proinflammatory cytokines.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, 36, Sanhao Street, Shenyang, 110004, China. daishy2014@163.com.

ABSTRACT

Background: Recent studies demonstrate that there are sex differences in the expression of angiotensin receptor type 2 (AT2-R) in the kidney and that AT2-R plays an enhanced role in regulating blood pressure (BP) in females. Also, brain AT2-R activation has been reported to negatively modulate BP and sympathetic outflow. The present study investigated whether the central blockade of endogenous AT2-R augments deoxycorticosterone acetate (DOCA)/salt-induced hypertension in both male and female rats.

Methods: All rats were subcutaneously infused with DOCA combined with 1% NaCl solution as the sole drinking fluid. BP and heart rate (HR) were recorded by telemetric transmitters. To determine the effect of central AT2-R on DOCA/salt-induced hypertension, male and female rats were intracerebroventricularly (icv) infused with AT2-R antagonist, PD123,319, during DOCA/salt treatment. Subsequently, the paraventricular nucleus (PVN) of the hypothalamus, a key cardiovascular regulatory region of the brain, was analyzed by quantitative real-time PCR and Western blot.

Results: DOCA/salt treatment elicited a greater increase in BP in male rats than that in females. Icv infusions of the AT2-R antagonist significantly augmented DOCA/salt pressor effects in females. However, this same treatment had no enhanced effect on DOCA/salt-induced increase in the BP in males. Real-time PCR and Western blot analysis of the female brain revealed that DOCA/salt treatment enhanced the mRNA and protein expression for both antihypertensive components including AT2-R, angiotensin-converting enzyme (ACE)-2, and interleukin (IL)-10 and hypertensive components including angiotensin receptor type 1 (AT1-R), ACE-1, tumor necrosis factor (TNF)-α, and IL-1β, but decreased mRNA expression of renin in the PVN. The central blockade of AT2-R reversed the changes in mRNA and protein expressions of ACE-2, IL-10, and renin, further increased the expressions of TNF-α and IL-1β, and kept higher the expressions of AT1-R, ACE-1, and AT2-R.

Conclusions: These results indicate that endogenous AT2-R activation in the brain plays an important protective role in the development of DOCA/salt-induced hypertension in females, but not in males. The protective effect of AT2-R in females involves regulating the expression of brain renin-angiotensin system components and proinflammatory cytokines.

No MeSH data available.


Related in: MedlinePlus

The effect of central infusion of AT2-R antagonist PD123,319 on DOCA/salt-induced hypertension in female rats. Daily mean arterial pressures (MAP) (A) and heart rate (HR) (B) before and during DOCA/salt treatments in intact females with or without central infusions of PD123,319. (C,D). Average changes in MAP and HR induced by DOCA/NaCl treatment in all groups. *P < 0.05 compared to baseline, #P < 0.05 compared to females with central infusion of PD123,319. DOCA, deoxycorticosterone acetate; icv, intracerebroventricular.
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Fig2: The effect of central infusion of AT2-R antagonist PD123,319 on DOCA/salt-induced hypertension in female rats. Daily mean arterial pressures (MAP) (A) and heart rate (HR) (B) before and during DOCA/salt treatments in intact females with or without central infusions of PD123,319. (C,D). Average changes in MAP and HR induced by DOCA/NaCl treatment in all groups. *P < 0.05 compared to baseline, #P < 0.05 compared to females with central infusion of PD123,319. DOCA, deoxycorticosterone acetate; icv, intracerebroventricular.

Mentions: The 1% NaCl alone (data not shown in Figure 2) or icv infusion of PD123,319 plus 1% NaCl had no effects on the basal MAP (104.6 ± 1.5 mmHg) and HR (375.9 ± 7.8 beats/min) in female rats. DOCA/salt treatment elicited a slight, but significant, increase in MAP in females with icv vehicle infusion (∆9.7 ± 1.8 mmHg, P < 0.05). Icv infusions of PD123,319 significantly augmented these DOCA/salt pressor effects (∆20.0 ± 3.2 mmHg, P < 0.05, Figure 2A,C). In contrast, systemic DOCA infusion produced a significant, comparable decrease in HR (Figure 2B,D, P > 0.05) in all groups when compared to rats given PD123,319 plus 1% NaCl.Figure 2


Brain endogenous angiotensin II receptor type 2 (AT2-R) protects against DOCA/salt-induced hypertension in female rats.

Dai SY, Peng W, Zhang YP, Li JD, Shen Y, Sun XF - J Neuroinflammation (2015)

The effect of central infusion of AT2-R antagonist PD123,319 on DOCA/salt-induced hypertension in female rats. Daily mean arterial pressures (MAP) (A) and heart rate (HR) (B) before and during DOCA/salt treatments in intact females with or without central infusions of PD123,319. (C,D). Average changes in MAP and HR induced by DOCA/NaCl treatment in all groups. *P < 0.05 compared to baseline, #P < 0.05 compared to females with central infusion of PD123,319. DOCA, deoxycorticosterone acetate; icv, intracerebroventricular.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4355980&req=5

Fig2: The effect of central infusion of AT2-R antagonist PD123,319 on DOCA/salt-induced hypertension in female rats. Daily mean arterial pressures (MAP) (A) and heart rate (HR) (B) before and during DOCA/salt treatments in intact females with or without central infusions of PD123,319. (C,D). Average changes in MAP and HR induced by DOCA/NaCl treatment in all groups. *P < 0.05 compared to baseline, #P < 0.05 compared to females with central infusion of PD123,319. DOCA, deoxycorticosterone acetate; icv, intracerebroventricular.
Mentions: The 1% NaCl alone (data not shown in Figure 2) or icv infusion of PD123,319 plus 1% NaCl had no effects on the basal MAP (104.6 ± 1.5 mmHg) and HR (375.9 ± 7.8 beats/min) in female rats. DOCA/salt treatment elicited a slight, but significant, increase in MAP in females with icv vehicle infusion (∆9.7 ± 1.8 mmHg, P < 0.05). Icv infusions of PD123,319 significantly augmented these DOCA/salt pressor effects (∆20.0 ± 3.2 mmHg, P < 0.05, Figure 2A,C). In contrast, systemic DOCA infusion produced a significant, comparable decrease in HR (Figure 2B,D, P > 0.05) in all groups when compared to rats given PD123,319 plus 1% NaCl.Figure 2

Bottom Line: Icv infusions of the AT2-R antagonist significantly augmented DOCA/salt pressor effects in females.However, this same treatment had no enhanced effect on DOCA/salt-induced increase in the BP in males.The protective effect of AT2-R in females involves regulating the expression of brain renin-angiotensin system components and proinflammatory cytokines.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, 36, Sanhao Street, Shenyang, 110004, China. daishy2014@163.com.

ABSTRACT

Background: Recent studies demonstrate that there are sex differences in the expression of angiotensin receptor type 2 (AT2-R) in the kidney and that AT2-R plays an enhanced role in regulating blood pressure (BP) in females. Also, brain AT2-R activation has been reported to negatively modulate BP and sympathetic outflow. The present study investigated whether the central blockade of endogenous AT2-R augments deoxycorticosterone acetate (DOCA)/salt-induced hypertension in both male and female rats.

Methods: All rats were subcutaneously infused with DOCA combined with 1% NaCl solution as the sole drinking fluid. BP and heart rate (HR) were recorded by telemetric transmitters. To determine the effect of central AT2-R on DOCA/salt-induced hypertension, male and female rats were intracerebroventricularly (icv) infused with AT2-R antagonist, PD123,319, during DOCA/salt treatment. Subsequently, the paraventricular nucleus (PVN) of the hypothalamus, a key cardiovascular regulatory region of the brain, was analyzed by quantitative real-time PCR and Western blot.

Results: DOCA/salt treatment elicited a greater increase in BP in male rats than that in females. Icv infusions of the AT2-R antagonist significantly augmented DOCA/salt pressor effects in females. However, this same treatment had no enhanced effect on DOCA/salt-induced increase in the BP in males. Real-time PCR and Western blot analysis of the female brain revealed that DOCA/salt treatment enhanced the mRNA and protein expression for both antihypertensive components including AT2-R, angiotensin-converting enzyme (ACE)-2, and interleukin (IL)-10 and hypertensive components including angiotensin receptor type 1 (AT1-R), ACE-1, tumor necrosis factor (TNF)-α, and IL-1β, but decreased mRNA expression of renin in the PVN. The central blockade of AT2-R reversed the changes in mRNA and protein expressions of ACE-2, IL-10, and renin, further increased the expressions of TNF-α and IL-1β, and kept higher the expressions of AT1-R, ACE-1, and AT2-R.

Conclusions: These results indicate that endogenous AT2-R activation in the brain plays an important protective role in the development of DOCA/salt-induced hypertension in females, but not in males. The protective effect of AT2-R in females involves regulating the expression of brain renin-angiotensin system components and proinflammatory cytokines.

No MeSH data available.


Related in: MedlinePlus