Author:
Loghman-Adham Mahmoud,Soto Carlos E.,Inagami Tadashi,Cassis Lisa
Abstract
Hypertension is a common complication of autosomal dominant polycystic kidney disease (ADPKD), often present before the onset of renal failure. A role for the renin-angiotensin system (RAS) has been proposed, but studies of systemic RAS have failed to show a correlation between plasma renin activity and blood pressure in ADPKD. Ectopic renin expression by cyst epithelium was first reported in 1992 (Torres VE, Donovan KA, Sicli G, Holley KE, Thibodeau ST, Carretero OA, Inagami T, McAteer JA, and Johnson CM. Kidney Int 42: 364–373, 1992). It is not known, however, whether other RAS components are also expressed by cysts in ADPKD. We show that, in addition to renin, angiotensinogen (AGT) is produced by some cysts and dilated tubules. Angiotensin-converting enzyme, ANG II type 1 receptor, and ANG II peptide are also present within cysts and in many tubules; and some cyst fluids contain high ANG II concentrations. Additionally, cyst-derived cells in culture continue to express the components of the RAS at both the protein and mRNA levels. We further show that renin is expressed primarily in cysts of distal tubule origin and in cyst-derived cells with distal tubule characteristics, whereas AGT is expressed primarily in cysts of proximal tubule origin and in cyst-derived cells with proximal tubule characteristics. Renin production by cyst-derived cells appears to be regulated by extracellular Na+concentration. Based on these observations, we propose a model of an autocrine/paracrine RAS in polycystic kidney disease, whereby overactivity of the intrarenal system results in sustained increases in intratubular ANG II concentrations.
Publisher
American Physiological Society
Reference63 articles.
1. Hereditary polycystic kidney disease (adult form): A microdissection study of two cases at an early stage of the disease
2. Differences in hormonal and renal vascular responses between normotensive patients with autosomal dominant polycystic kidney disease and unaffected family members
3. Hypertension in autosomal dominant polycystic kidney disease
4. Casarini DE, Boim MA, Stella RC, Krieger-Azzolini MH, Krieger JE, and Schor N.Angiotensin I-converting enzyme activity in tubular fluid along the rat nephron.Am J Physiol Renal Physiol272: F405–F409, 1997.
5. Cassis L, Laughter A, Fettinger M, Akers S, Speth R, Burke G, King V, and Dwoskin L.Cold exposure regulates the renin-angiotensin system.J Pharmacol Exp Ther286: 718–726, 1998.
Cited by
125 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献