Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage.

Abstract

Tonic basal release of nitric oxide (NO) by vascular endothelial cells controls blood pressure (BP) in the basal state. In these studies we investigated the effects of chronic inhibition of basal NO synthesis in the rat for a 2-mo period. Significant systemic hypertension developed in chronically NO-blocked rats compared to controls. Marked renal vasoconstriction was also observed with elevations in glomerular blood pressure (PGC) and reductions in the glomerular capillary ultrafiltration coefficient (Kf). Chronically NO-blocked rats also develop proteinuria and glomerular sclerotic injury compared to controls. These studies therefore describe a new model of systemic hypertension with glomerular capillary hypertension and renal disease due to chronic blockade of endogenous NO synthesis. These observations highlight the importance of the endogenous NO system in control of normal vascular tone and suggest that hypertensive states may result from relative NO deficiency. (J. Clin. Invest. 1992. 90:278-281.) Key words: nitric oxide * hypertension glomerulus * single nephron glomerular filtration rate

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

“…Consequently, it is not surprising that, in the clinic as well as in animal models, NO deficiency is causally related to kidney disease. NOS inhibition leads dose dependently to severe hypertension, proteinuria, glomerulosclerosis, and reduced glomerular filtration rate (GFR) and renal plasma flow (RPF) 13, 14. In patients with diabetic nephropathy, NO generation is limited by endothelial dysfunction 15.…”

Reduced production of nitric oxide during haemodialysis

“…A new model of hypertension has been developed by chronic inhibition of NO synthesis using the active inhibitor NG-nitro-l-arginine methyl ester. 3,4 Chronic NO blockade causes dosedependent increases in systolic blood pressure. Renal failure is often accompanied by hypertension, and interestingly, patients with renal failure have been shown to possess high levels of guanidinosubstituted analogues of l-arginine compounds that inhibit NO synthesis.…”

Asymmetric Dimethylarginine Produces Vascular Lesions in Endothelial Nitric Oxide Synthase–Deficient Mice

“…[1][2][3][4][5] Long-term treatment with L-NAME is known to cause arteriosclerotic coronary lesions, especially at microvascular levels, in experimental animals. 8,9 This model with L-NAME is regarded as a useful animal model for examining the protective roles of endothelium-derived NO in the pathogenesis of arteriosclerosis. 8,9 See cover However, it is controversial whether these vascular effects of L-NAME are caused primarily by the inhibition of endothelial NO synthesis for the following reasons: first, the importance of endothelium-derived NO decreases as the vessel size becomes smaller, 10 whereas L-NAME-induced vascular lesions are prominent at microvascular levels; 8 second, long-term treatment with L-NAME does not reduce eNOS activity; 11 third, multiple actions of L-NAME other than simple inhibition of NO synthesis have been reported.…”