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NITRIC OXIDE AND SUPEROXIDE INTERACTIONS IN THE KIDNEY AND THEIR IMPLICATION IN THE DEVELOPMENT OF SALT‐SENSITIVE HYPERTENSION
Author(s) -
Majid Dewan SA,
Kopkan Libor
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04642.x
Subject(s) - nitric oxide , nitric oxide synthase , chemistry , superoxide , angiotensin ii , superoxide dismutase , renal function , medicine , kidney , endocrinology , oxidative stress , renal sodium reabsorption , pharmacology , reabsorption , blood pressure , enzyme , biochemistry
SUMMARY1 Enhanced superoxide () activity as a result of the inhibition of the superoxide dismutase (SOD) enzyme results in vasoconstrictor and antinatriuretic responses in the canine kidney; these responses were shown to be greatly enhanced during inhibition of nitric oxide synthase (NOS). Glomerular filtration rate remained mostly unchanged during SOD inhibition in the intact nitric oxide (NO) condition, but was markedly reduced during NOS inhibition. These findings indicate that endogenous NO has a major renoprotective effect against by acting as an anti‐oxidant. Nitric oxide synthase inhibition was also shown to enhance endogenous activity. 2 Experiments in our laboratory using dogs, rats and gene knockout mice have shown that renal vasoconstrictor and antinatriuretic responses to acute or chronic angiotensin (Ang) II administration are mediated, in part, by generation. In the absence of NO, enhanced activity largely contributes to AngII‐induced renal tubular sodium reabsorption. Acute or chronic treatment with the scavenger tempol in experimental models of hypertension (induced by chronic low‐dose treatment with AngII and NO inhibitors) causes an improvement in renal haemodynamics and in excretory function, abolishes salt sensitivity and reduces blood pressure. 3 The present mini review also discusses related studies from many other laboratories implicating a role for and its interaction with NO in the development of salt‐sensitive hypertension. 4 Overall, the collective data support the hypothesis that an imbalance between the production of NO and in the kidney primarily determines the condition of oxidative stress that alters renal haemodynamics and excretory function leading to sodium retention and, thus, contributes to the development of salt‐sensitive hypertension.