Involvement of angiotensin II and endothelin in matrix protein production and renal sclerosis.
OBJECTIVE
To review the evidence that links angiotensin II and endothelin as growth factors and as modifiers of extracellular matrix synthesis in renal cells, with particular reference to the effects of angiotensin converting enzyme (ACE) inhibition in models of renal injury.


METHODS
In cultured mesangial cells, both angiotensin II and endothelin promote contraction, proliferation/hypertrophy, signal transduction pathways, the activation of early growth genes, and the generation of inflammatory mediators, cytokines and growth factors. Both hormones have been shown to promote the synthesis of fibronectin and collagen in a dose-dependent manner. ACE inhibition attenuates the effect of endothelin-1, one of three isoforms of endothelin.


METHODS
In experimental models of renal injury, chiefly in those characterized by increased intraglomerular pressure, ACE inhibition has reduced proteinuria and glomerular and interstitial sclerosis.
ACE inhibition has been shown to have major beneficial effects in patients with diabetic nephropathy, even in those with normal blood pressure.


CONCLUSIONS
Although the renal-protective effects of ACE inhibitors in experimental and human renal injury may reflect systemic and/or local hemodynamic effects of these drugs, their modulatory actions on extracellular matrix synthesis and proteinuria may contribute to the benefit of ACE-inhibitor therapy.
Ruíz-Ortega
M
M
Jiménez Díaz Foundation, Autónoma University, Madrid, Spain.
Gómez-Garre
D
D
Alcázar
R
R
Palacios
I
I
Bustos
C
C
González
S
S
Plaza
J J
JJ
González
E
E
Egido
J
J
D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000502:physiology; D016232:Endothelins / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D012598:Sclerosis
D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D000804:Angiotensin II