Renal Perfusion Pressure Determines Infiltration of Leukocytes in the Kidney of Rats With Angiotensin II–Induced Hypertension

Abstract

The present study examined the extent to which leukocyte infiltration into the kidneys in Ang II (angiotensin II)-induced hypertension is determined by elevation of renal perfusion pressure (RPP). Male Sprague-Dawley rats were instrumented with carotid and femoral arterial catheters for continuous monitoring of blood pressure and a femoral venous catheter for infusion. An inflatable aortic occluder cuff placed between the renal arteries with computer-driven servo-controller maintained RPP to the left kidney at control levels during 7 days of intravenous Ang II (50 ng/kg per minute) or vehicle (saline) infusion. Rats were fed a 0.4% NaCl diet throughout the study. Ang II–infused rats exhibited nearly a 50 mm Hg increase of RPP (carotid catheter) to the right kidney while RPP to the left kidney (femoral catheter) was controlled at baseline pressure throughout the study. As determined at the end of the studies by flow cytometry, right kidneys exhibited significantly greater numbers of T cells, B cells, and monocytes/macrophages compared with the servo-controlled left kidneys and compared with vehicle treated rats. No difference was found between Ang II servo-controlled left kidneys and vehicle treated kidneys. Immunostaining found that the density of glomeruli, cortical, and outer medullary capillaries were significantly reduced in the right kidney of Ang II–infused rats compared with servo-controlled left kidney. We conclude that in this model of hypertension the elevation of RPP, not Ang II nor dietary salt, leads to leukocyte infiltration in the kidney and to capillary rarefaction.

Acute Increase of Renal Perfusion Pressure Causes Rapid Activation of mTORC1 (Mechanistic Target Of Rapamycin Complex 1) and Leukocyte Infiltration

“…We have recently reported, by servocontrolling renal perfusion pressure (RPP), that the chronic elevation of RPP drives the infiltration of inflammatory cells into the kidneys in 2 models of hypertension, Dahl salt-sensitive (SS) rats fed a high-salt diet 2 and Sprague-Dawley (SD) rats infused with angiotensin II. 3 We further showed that T-cell deficiency attenuates but does not eliminate the development of salt-sensitivity 4 and angiotensin II-mediated hypertension. 5 Similarly, CCL2 (C-C motif chemokine ligand 2) inhibition 6 has been found to attenuate salt-sensitive hypertension but only after the initial rise of blood pressure is clearly established, consistent with the leukocyte infiltration being secondary to hypertension.…”

Gut-Immune-Kidney Axis: Influence of Dietary Protein in Salt-Sensitive Hypertension

“…We hypothesize (Figure 1), 6,7 based upon data from Dahl SS and angiotensin II-hypertensive rats, 51,52,53 that an initial increase in blood pressure is transmitted to the renal vasculature and mediates the infiltration of immune cells into the kidney. The mechanism is unclear, but it is possible that the elevated perfusion pressure results in tissue damage and triggers the migration of innate and adaptive immune cells into the kidney.…”

Treatment of renal interstitial fibrosis with an agonistic Tie2 monoclonal antibody via amelioration of peritubular capillary lesions in a mouse model of nephropathy

“…There is increasing evidence to show that peritubular capillaries play an important role in CKD and are a key regulator of CKD progression [39]. Peritubular capillary rarefaction is found not only in diabetic nephropathy [40] and hypertensive nephropathy [41], but also in IgA nephropathy [42], congenital nephrotic syndrome [43], lupus nephritis [44], and polycystic kidney disease [45]. Thus, protecting peritubular capillaries is a crucial approach to alleviating renal brosis [46][47][48][49].…”