Angiotensin II modulates glomerular capillary permselectivity in rat isolated perfused kidney.

Abstract

Studies in experimental animals and humans have documented that inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors reduces urinary protein excretion rate and retards the development of renal injury. Here we sought to investigate whether angiotensin II (All) modified the size-selective properties to macromolecules of the glomerular capillary barrier in isolated perfused rat kidney preparation. Compared with basal values, continuous All infusion into the renal artery at the rate of 3 or 8 ng/min, but not at 0.6 ng/min, induced a progressive and significant increase in urinary protein excretion rate. Evaluation of the sieving properties of the glomerular barrier by fractional clearance of polydisperse Ficoll showed that All significantly enhanced the filtration of tracer molecules of radil > or = 34A. All-induced changes in urinary protein excretion rate and in Ficoll fractional clearance were completely prevented by pretreatment with the specific All Type 1 receptor antagonist SR 47436.

Moderate salt restriction with or without paricalcitol in type 2 diabetes and losartan-resistant macroalbuminuria (PROCEED): a randomised, double-blind, placebo-controlled, crossover trial

“…23 Angiotensin II might directly increase the glomerular barrier permeability to plasma macromolecules and proteinuria, independent of changes in systemic haemo dynamics and even intraglomerular capillary presssure. 24 Independent of BP control, intrarenal ACE activation is associated with accelerated progression of experimental chronic kidney disease 2,4 and enhanced proteinuria and faster loss of renal function in patients with diabetic and non-diabetic chronic nephropathies. 8,17 However, acti vation of the vitamin D receptor suppresses renin trans cription, 25 so vitamin D analogues might act as negative endocrine regulators of the RAS, in particular in com bination with ARBs, 11 as in our study population.…”

Combining Neprilysin Inhibitor With AT2R Agonist Is Superior to Combination With AT1R Blocker in Providing Reno-Protection in Obese Rats

“…While the exact involvement in the pathophysiological mechanisms of renal and/or cardiovascular disease are not yet fully understood, it is known that high renin levels also have detrimental effects independent from Ang II, via binding (pro)renin receptor (Nguyen et al, 2004). Moreover, high concentrations of tissue Ang II induce pro-fibrotic, pro-inflammatory, and prohypertrophic effects that damage the kidney (Ames et al, 2019), influence urinary excretion of albumin (Clavant et al, 2003), and increased the fractional excretion of protein (Lapinski et al, 1996). Despite the involvement of alternate pathways involving enzymes such as chymase in the generation of Ang II, the predominant enzymes involved in Ang II generation include renin and ACE.…”

Comparative Evaluation of Renoprotection by Valsartan vs Trandolapril in Streptozotocin Induced Diabetic Nephropathy

“…Lapinski et al 15 explained that the angiotensin II via increase in glomerular capillary pressure. They suggested that a vicious cycle is established in which the changes in renal hemodynamics due to the loss of nephrons lead to proteinuria which is then followed by the loss of more nephrons.…”