Effects Of Angiotensin-(1-7) On Blood Pressure In Habenular Nncleus(Hb)

Angiotensin-(1-7) [Ang-(1-7)] has been considered as aninactive metabolite of angiotensin II (Ang II) for a long time. However,recent studies have shown that Ang-(1-7) is a real hormone of theangiotensin system which plays an important role in the modulation ofcardiovascular function. Ang-(1-7) is produced by the hydrolysis ofAng I by prolyl endopeptidase (PE) or neutral endopeptidase ormetallo endopeptidase. Ang-(1-9) is produced by the hydrolysis ofAng I by ACE2. ACE can hydrolyze Ang-(1-9) to Ang-(1-7). Inaddition, ACE2 can hydrolyze Ang II to Ang-(1-7). In fact, the ACE2catalytic efficiency is 400-fold higher with Ang II as a substrate thanwith Ang I. Ang-(1-7) has the opposing effects of Ang II in mostaspects. Much evidence suggests that the habenular nucleus (Hb)plays a very important role in the control of cardiovascular activities.Ang II can influence cardiovascular activities in the habenular nucleus(Hb).Up to now it has not been reported whether Ang-(1-7) caninfluence cardiovascular activities in the habenular nucleus (Hb). Thepresent study was designed to investigate the effect of Ang-(1-7) onblood pressure (BP) in the Hb by the techniques of microinjection.Inaddition, as much evidence suggests that Ang-(1-7) can increase ordecrease blood pressure (BP) in many areas in central system, wedesigned to investigate the effect of Ang-(1-7) on blood pressure (BP)by the techniques of intracerebroventricular (ICV) microinjection.Experiments were performed on 84 male Wistar (240-260g) ratsanesthetized with urethane (1g/kg) and ventilated with room air freely.A catheter was inserted into arteria carotis communis for arterialpressure measurement. Next, the animals were placed in a stereotaxicframe. The dorsal surface of the brain stem was exposed by a limitedcraniotomy and incision of the membrane and meninges. Arterialpressure were continuously monitored with a solid-state strain gaugetransducer coupled to a graph. Microinjections of Ang-(1-7) (n=18),Ang779(n=18), sterile saline (NaCl 0.9%, (n=6), or vehicle (n=6) in avolume of 3μl were made over 1-min period into the lateral ventricle.Microinjections of Ang779 (n=18), Ang779+AngⅡ (n=6), AngⅡ(n=6), or vehicle (n=6) in a volume of 0.2μl were made over30-second period into the Hb. Microinjections were made with a glassmicropipette.1,ICV infusion of Ang-(1-7) produced a significant increase inmean arterial pressure (MAP) (n=18, P<0.05). ICV infusion of salinecould not significantly alter MAP. There is significant difference in thechange of MAP between group saline and group Ang-(1-7) (P<0.01).ICV infusion of (D-Ala7) -Ang-(1-7) (Ang779), a selective antagonistof Ang-(1-7) receptor, caused a complicated result in MAP (n=18).MAP may be increased or decreased or remained unchanged.It had nostatistical significance. ICV infusion of vehicle produced a significantincrease in mean arterial pressure (MAP) (n=6, P<0.05). The results ofICV infusion of Ang779 could not exclude the interferer of vehicle.These results indicate that there exists endogenous Ang-(1-7) receptorin the lateral ventricle, which contribute to maintenance bloodpressure in physiological condition.2,Microinjection of (D-Ala7)-Ang-(1-7) (Ang779) into the Hbproduced a dose-dependent increase in mean arterial pressure (MAP)(n=18, P<0.05). Microinjection of vehicle (n=6) into the same sitecould not significantly alter MAP. There is significant difference in thechange of MAP between group vehicle and group Ang779 100ng,200ng (P<0.01). These results indicate that there exists endogenousAng-(1-7) receptor in Hb, which contribute to maintenance bloodpressure in physiological condition.3,Microinjection of Ang779+AngⅡ into the Hb produced asignificant increase in mean arterial pressure (MAP) (n=6, P<0.05).There is significant difference in the change of MAP between groupvehicle and group Ang779+AngⅡ (P<0.01). These results indicatethat Ang779 could not inhibit the effect of AngⅡ.Taken together, renin-angiotensin system may modulate bloodpressure in Hb and lateral ventricle. It may include two arms. one isACE and AngⅡ. The other is ACE2 and Ang-(1-7).