Angiotensin-(1-7) attenuates hypertension and cardiac hypertrophy via modulation of nitric oxide and neurotransmitter levels in the paraventricular nucleus in salt-sensitive hypertensive rats

Fig. 1. The effect of an intracerebroventricular (ICV) infusion of angiotensin-(1-7) [Ang-(1-7)] on the mean arterial pressure (MAP) (A) and plasma norepinephrine (NE) levels (B) in rats receiving a normal-salt diet (NS, 0.3% NaCl) or a high-salt diet (HS, 8% NaCl) is depicted. HS rats had increased MAP and plasma NE levels compared to NS rats. Chronic ICV infusions of Ang-(1-7) attenuated MAP and plasma NE levels. Values are mean ± SEM. *P < 0.05 versus NS groups [NS + vehicle or NS + Ang-(1-7)]; †P < 0.05 HS + Ang-(1-7) versus HS + vehicle.

Fig. 2. The effect of an intracerebroventricular (ICV) infusion of Ang-(1-7) on cardiac hypertrophy in rats receiving a normal-salt diet (NS) or a high-salt diet (HS) is depicted. HS rats had elevated cardiac hypertrophy as assessed by the whole heart weight/body weight (WHW/BW) ratio (A), whole heart weight/tibia length (WHW/TL) ratio (B), and left ventricular weight/tibia length (LVW/TL) ratio (C), which were attenuated after ICV infusion of Ang-(1-7). Values are mean ± SEM. *P < 0.05 versus NS groups [NS + vehicle or NS + Ang-(1-7)]; †P < 0.05 HS + Ang-(1-7) versus HS + vehicle.

Fig. 3. The effect of an intracerebroventricular (ICV) infusion of Ang-(1-7) on cardiac atrial natriuretic peptide (ANP) and myosin heavy chain (MHC) protein expression in the left ventricular tissue of the heart in rats receiving a normal-salt diet (NS) or a high-salt diet (HS) is depicted. Compared to NS rats, HS rats showed a significant increase in ANP and MHC protein expression in the left ventricular tissue of the heart, which decreased after ICV infusion of Ang-(1-7). (A) A representative immunoblot is shown. (B) Densitometric analysis of protein expression in the PVN for ANP and MHC is shown. Values are mean ± SEM. *P < 0.05 versus NS groups [NS + vehicle or NS + Ang-(1-7)]; †P < 0.05 HS + Ang-(1-7) versus HS + vehicle.

Fig. 4. The effect of an intracerebroventricular (ICV) of Ang-(1-7) on the levels of nitric oxide (NO) (A), norepinephrine (NE) (B), glutamate (C) and γ-aminobutyric acid (GABA) (D) within the PVN in rats receiving a normal-salt diet (NS) or a high-salt diet (HS) is depicted. Compared to NS rats, HS rats had higher levels of NE and glutamate and lower levels of NO and GABA. Chronic ICV infusion of Ang-(1-7) reduced NE and glutamate levels and increased NO and GABA levels in the PVN of HS rats. Values are mean ± SEM. *P < 0.05 versus NS groups [NS + vehicle or NS + Ang-(1-7)]; †P < 0.05 HS + Ang-(1-7) versus HS + vehicle.

Fig. 5. The effects of an intracerebroventricular (ICV) infusion of Ang-(1-7) on tyrosine hydroxylase (TH) expression in the PVN in rats receiving a normal-salt diet (NS) or a high-salt diet (HS) is depicted. Compared to NS rats, HS rats had increased TH expression. Chronic ICV infusions of Ang-(1-7) decreased TH in the PVN of HS rats. (A) Immunohistochemistry for TH expression in the PVN is shown. (B) A bar graph of TH positive neurons in the PVN is shown. (C) A representative immunoblot and densitometric analysis of protein expression of TH in the PVN is shown for different groups. Values are mean ± SEM. *P < 0.05 versus NS groups [NS + vehicle or NS + Ang-(1-7)]; †P < 0.05 HS + Ang-(1-7) versus HS + vehicle.

Fig. 6. The effect of an intracerebroventricular (ICV) infusion of Ang-(1-7) on 67 kDa isoform of glutamate decarboxylase (GAD67) expression in the PVN of rats receiving a normal-salt diet (NS) or a high-salt diet (HS) is depicted. Compared to NS rats, HS rats had decreased GAD67 expression. Chronic ICV infusions of Ang-(1-7) increased GAD67 expression in the PVN of HS rats. (A) Immunofluorescence for GAD67 expression in the PVN is shown. (B) A bar graph of GAD67 positive neurons in the PVN is shown. (C) A representative immunoblot and densitometric analysis of GAD67 protein expression in the PVN is shown for different groups. Values are mean ± SEM. *P < 0.05 versus NS groups [NS + vehicle or NS + Ang-(1-7)]; †P < 0.05 HS + Ang-(1-7) versus HS + vehicle.