Angiotensin II and angiotensin-(1-7) in paraventricular nucleus modulate cardiac sympathetic afferent reflex in renovascular hypertensive rats - PubMed (original) (raw)
Angiotensin II and angiotensin-(1-7) in paraventricular nucleus modulate cardiac sympathetic afferent reflex in renovascular hypertensive rats
Hai-Jian Sun et al. PLoS One. 2012.
Abstract
Background: The enhanced cardiac sympathetic afferent reflex (CSAR) is involved in the sympathetic activation that contributes to the pathogenesis and progression of hypertension. Activation of AT(1) receptors by angiotension (Ang) II in the paraventricular nucleus (PVN) augments the enhanced CSAR and sympathetic outflow in hypertension. The present study is designed to determine whether Ang-(1-7) in PVN plays the similar roles as Ang II and the interaction between Ang-(1-7) and Ang II on CSAR in renovascular hypertension.
Methodology/principal findings: The two-kidney, one-clip (2K1C) method was used to induce renovascular hypertension. The CSAR was evaluated by the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to epicardial application of capsaicin in sinoaortic-denervated and cervical-vagotomized rats with urethane and α-chloralose anesthesia. Either Ang II or Ang-(1-7) in PVN caused greater increases in RSNA and MAP, and enhancement in CSAR in 2K1C rats than in sham-operated (Sham) rats. Mas receptor antagonist A-779 and AT(1) receptor antagonist losartan induced opposite effects to Ang-(1-7) or Ang II respectively in 2K1C rats, but losartan had no effects in Sham rats. Losartan but not the A-779 abolished the effects of Ang II, while A-779 but not the losartan blocked the effects of Ang-(1-7). PVN pretreatment with Ang-(1-7) dose-dependently augmented the RSNA, MAP, and CSAR responses to the Ang II in 2K1C rats. Ang II level, AT(1) receptor and Mas receptor protein expression in PVN increased in 2K1C rats compared with Sham rats but Ang-(1-7) level did not.
Conclusions: Ang-(1-7) in PVN is as effective as Ang II in enhancing the CSAR and increasing sympathetic outflow and both endogenous Ang-(1-7) and Ang II in PVN contribute to the enhanced CSAR and sympathetic outflow in renovascular hypertension. Ang-(1-7) in PVN potentiates the effects of Ang II in renovascular hypertension.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
Figure 1. Effects of PVN microinjection of saline, Ang II (0.3 nmol), Ang-(1-7) (0.3 nmol) and Ang II+Ang-(1-7) on the baseline RSNA and MAP and CSAR.
The CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin (1 nmol). Values are mean ± SE. * P<0.05 compared with saline. † P<0.05 compared with Sham. ‡ P<0.05 compared with Ang II alone. # P<0.05 compared with Ang-(1-7) alone. n = 6 for each group.
Figure 2. Effects of the PVN microinjection of saline and three doses of Ang-(1-7) (0.03, 0.3 and 3 nmol) on the baseline RSNA and MAP and CSAR.
The CSAR was evaluated by the RSNA and MAP response to epicardial application of capsaicin (1 nmol). Values are mean ± SE. *P<0.05 compared with saline. † P<0.05 compared with Sham. n = 6 for each group.
Figure 3. Representative recordings showing the effects of PVN pretreatment with saline or Ang-(1-7) (3 nmol) on the CSAR responses to the Ang II (0.3 nmol) in Sham and 2K1C rats.
The CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin (1 nmol).
Figure 4. Effects of PVN pretreatment with saline and three doses of Ang-(1-7) (0.03, 0.3 and 3 nmol) on the baseline RSNA and MAP and CSAR responses to the Ang II (0.3 nmol).
The CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin (1 nmol). Values are mean ± SE. *P<0.05 compared with saline. † P<0.05 compared with Sham. n = 6 for each group.
Figure 5. Effects of PVN microinjection of saline, Ang II (0.3 nmol), losartan (50 nmol), losartan+Ang II and A-779 (3 nmol) +Ang II on the baseline RSNA and MAP and CSAR.
The CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin (1 nmol). Values are mean ± SE. * P<0.05 compared with saline. † P<0.05 compared with Sham. ‡ P<0.05 compared with Ang II alone. n = 6 for each group.
Figure 6. Effects of PVN microinjection of saline, Ang-(1-7) (0.3 nmol), A-779 (3 nmol), A-779+Ang-(1-7) and losartan (50 nmol) +Ang-(1-7) on the baseline RSNA and MAP and CSAR.
The CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin (1 nmol). Values are mean ± SE. * P<0.05 compared with saline. † P<0.05 compared with Sham. ‡ P<0.05 compared with Ang-(1-7) alone. n = 6 for each group.
Figure 7. Ang II level (A), Ang-(1-7) level (B), AT1 receptor protein expression (C) and Mas receptor protein expression (D) in PVN in Sham rats and 2K1C rats.
Values are mean ± SE. * P<0.05 compared with Sham rats. n = 5 for each group.
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