ACE-inhibitor Suppresses the Apoptosis Induced by Endoplasmic Reticulum Stress in Renal Tubular in Experimental Diabetic Rats

Abstract

Increased tubular apoptosis in experimental diabetic rats is attenuated by blockade of the renin-angiotensin system with an ACE inhibitor, which might be in an association with reduced endoplasmic reticulum stress.

Endoplasmic Reticulum Stress Implicated in the Development of Renal Fibrosis

“…These findings suggest that an angiotensin II type 1 receptor-dependent pathway contributes to the activation of ER stress and cell apoptosis (19). Recent reports also suggest that angiotensin-converting enzyme inhibitor suppresses the apoptosis induced by ER stress in renal tubules of experimental diabetic rats (40). Some may object to the numerous mechanisms of the renin-angiotensin system blockade involved in cell protection, including reversing hypoxia, ischemia and hypertension and suppressing reactive oxygen species; however, cellular stress mechanisms frequently operate through complex networks.…”

Diabetic nephropathy: a disorder of oxygen metabolism?

“…in addition to the protective benefits conferred by angiotensin ii type 1 receptor (at 1 ) blockade and lowering blood pressure, angiotensin-iireceptor antagonists (or angiotensin-converting-enzyme inhibitors) have the unique ability to correct not only tissue hypoxia (by an increase in postglomerular peritubular blood flow 63 or through receptor activation of angiotensin ii type 2 receptor and no production 64 ) but also to correct oxidative stress and nitrosative stress, 65,66 carbonyl stress and advanced glycation, 67,68 redox imbalance 69 and er stress. 70 to investigate the mechanisms by which angiotensin-iireceptor antagonists confer these protective benefits, we synthesized a novel, nontoxic angiotensin-ii-receptor antagonist derivative, r-147,176, characterized by a weak affinity for the at 1 (6,700 times less effective than olmesartan in at 1 -binding inhibition), but with an ability to confer striking inhibition of oxidative stress and advanced glycation. 71 Despite a minimal effect on blood pressure, r-147,176 provided notable reno protection in two differ ent rat models of type 2 dia betes-(sHr/ nDmcr-cp and Zucker diabetic fatty rats).…”

Mechanisms of Diabetic Nephropathy – Old Buddies and Newcomers Part 1

“…The therapeutic benefi t of an RAS-inhibition in secondary prevention is partially independent of the blood pressure lowering eff ect [45] . These additional eff ects may refl ect the inhibition of angiotensin II, a potent vasoconstrictor and inductor of TGF β , VEGF and ROS generation.…”