Renal vascular responses to angiotensin II infusion in two kidneys-one clip hypertensive rats under partial ischemia/reperfusion with and without ischemia preconditioning: the roles of AT1R blockade and co-blockades of AT1R and MasR

Abstract

Background and purpose: The renin-angiotensin system activation, partial ischemia/reperfusion (IR) injury, and hypertension contribute to the development of acute kidney injury. The study aims to look at the vascular responses of angiotensin II (Ang II) during Ang II type 1 receptor (AT1R) blockade (losartan) or co-blockades of AT1R and Mas receptor (A779) in two kidneys one clip (2K1C) hypertensive rats which subjected to partial IR injury with and without ischemia preconditioning (IPC).

Experimental approach: Thirty-three 2K1C male Wistar rats with systolic blood pressure ≥ 150 mmHg were divided into three groups of sham, IR, and IPC + IR divided into two sub-groups receiving losartan or losartan + A779. The IR group had 45 min partial kidney ischemia, while the IPC + IR group had two 5 min cycles of partial ischemia followed by 10 min of reperfusion and then 45 min of partial kidney ischemia followed by reperfusion. The sham group was subjected to similar surgical procedures except for IR or IPC.

Findings/results: Ang II increased mean arterial pressure in all the groups, but there were no significant differences between the sub-groups. A significant difference was observed in the renal blood flow response to Ang II between two sub-groups of sham and IR groups treated with AT1R blockade alone or co-blockades of AT1R + A779.

Conclusion and implications: These findings demonstrated the significance of AT1R and Mas receptor following partial renal IR in the renal blood flow responses to Ang II in 2K1C hypertensive rats.

Keywords: AT1R; Angiotensin II; MasR; Renal ischemia/reperfusion; Two kidneys-one clip.

Fig. 1

Induction of the 2K1C hypertensive model. (A) The right renal artery was isolated, and (B) two kidneys one clip was induced by placing a silver U-shaped clip (0.2 mm inner diameter) around it.

Fig. 2

Twenty eight days following clipping and two kidneys one clip renovascular hypertension induction, the rats were anesthetized with urethane. (A) After tracheal catheterization, (B) the left carotid artery was isolated and catheterized using a polyethylene catheter. Also, (C) the left jugular vein and (D) femoral artery and bladder were catheterized.

Fig. 3

(A-C) The left kidney was isolated and put in the kidney cup. (D) The abdominal aorta was isolated, followed by placing an adjustable occluder around it to regulate renal perfusion pressure throughout angiotensin II administration and induction of partial ischemia. (E) To measure renal blood flow, the renal artery was isolated and (F) an ultrasonic flow probe with a diameter of 0.7 mm connected to a flow meter was placed around it.

Fig. 4

Protocol of study. 2K1C, Two kidney one- clip; IR, ischemia-reperfusion; IPC, ischemia preconditioning.

Fig. 5

The effect of antagonist. MAP, RPP, RBF per g kidney weight, and RVR were evaluated 30 min post losartan and losartan + A779 infusion. The P-values were obtained using ANOVA for repeated measures. MAP, Mean arterial pressure; RPP, renal perfusion pressure; RBF, renal blood flow; RVR, renal vascular resistance.

Fig. 6

The effect of graded angiotensin II administration. The percentage change of mean MAP, RPP, RBF, and RVR was evaluated after graded angiotensin II infusion. The P-values were obtained using ANOVA for repeated measures. MAP, Mean arterial pressure; RPP, renal perfusion pressure; RBF, renal blood flow; RVR, renal vascular resistance.