Renal kallikrein-kinin system damage and salt sensitivity: insights from experimental models.
The importance of tubulointerstitial injury in the pathophysiology of human essential hypertension, and particularly salt sensitivity, is increasingly recognized. Since the renal kallikrein-kinin system (KKS) is located in the tubulointerstitial region of the kidney it is reasonable to expect that injury to this area, whatever the cause, may impair KKS production and compromise its role in blood pressure regulation. In this review we discuss evidence of injury in the renal kallikrein-producing structures in three different experimental models characterized by prominent tubulointerstitial lesions: subtotal nephrectomy; inhibition of nitric oxide synthase; and overload proteinuria. These three experimental models have in common the development of important tubulointerstitial damage and salt-sensitive hypertension expressed after the initial injury has ceased. In these three models, reduced KKS activity may contribute to the establishment of a pathophysiologic state characterized by unopposed hyperactivity of the renin-angiotensin system, resulting in salt retention.
Ardiles
Leopoldo G
LG
Department of Nephrology, Universidad Austral de Chile, Valdivia, Chile. lardiles@uach.cl
Figueroa
Carlos D
CD
Mezzano
Sergio A
SA
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D016234:Kallikrein-Kinin System; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009392:Nephrectomy / Q000379:methods; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011507:Proteinuria / Q000150:complications / Q000378:metabolism / Q000473:pathology; D012965:Sodium Chloride / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester