Renin/prorenin receptor, (P)RR, in end-organ damage: current issues in 2007.
We present a critical review on emerging concepts on the role of (pro)renin receptor, (P)RR, in diabetic and hypertensive nephropathy. Discovery of nonproteolytic activation of prorenin by the receptor led to nontoxic peptidic prorenin receptor blocker. The receptor blocker permitted long-term in vivo studies on the role of (P)RR in diabetic and hypertensive end-organ damage. Chronic infusion of receptor blocker prevented streptozotocin diabetic nephropathy and attenuated hypertensive cardiomyopathy and nephropathy. In support of these results, transgenic rats overexpressing the receptor nonselectively developed renal glomerulopathy with aging without elevating blood glucose or blood pressures. It indicated that the receptor overexpression alone is sufficient for end-organ damage, and diabetes mellitus and hypertension induce the end-organ damage by increasing (P)RR expression. We propose that (P)RR is a pivotal link between pathogenesis of diabetes mellitus and end-organ damage. (P)RR seems to activate this mechanism largely by activating receptor signals rather than by local angiotensin II. We realized that (P)RR blocker is a competitive inhibitor against prorenin, and its efficiency depends on ambient concentration of prorenin and renin. Optimization of the condition will be necessary to maximize the inhibitory and therapeutic effects.
Inagami
Tadashi
T
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Nakagawa
Tsutomu
T
Ichihara
Atsuhiro
A
Suzuki
Fumiaki
F
Itoh
Hiroshi
H