ABSTRACTin vitro and in vivo

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ABSTRACT. To clarify the role of nitric oxide (NO) in hemodialysis (HD)-related hypotension, the relationship between plasma NO metabolites (NOx) and blood pressure changes, and the effect of N G -monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, on changes in blood pressure were evaluated in an experimental renal dysfunctional dog model. In order to create a renal dysfunction model, gentamicin was administered to male beagles in which 7 of 8 renal artery branches had been ligated. Normal renal functional and dy sfunctional dogs underwent 3 hr of HD per day for 3 days. HD induced a transient decrease in mean blood pressure in the normal renal functional dogs. In renal dysfunctional dogs, a continuous hypotension occurred with a gradual increase in the plasma NOx conce ntration during HD. Although L-NMMA prevented the fall in blood pressure, it did not significantly change the plasma NOx concentration during HD. These results suggest that NO contributes to HD-related hypotension in renal dysfunctional dogs but the plasma NOx concentration does not reflect the change in blood pressure. KEY WORDS: hemodialysis-related hypotension, L-NMMA, nitric oxide, renal dysfunctional dog.J. Vet. Med. Sci. 66(1): 53-57, 2004 Hemodialysis (HD) is an established form of therapy for renal dysfunction which has developed since the first study was carried out on a rabbit in 1912 [1]. Nevertheless, HD causes many complications. Hypotension is a major complication of HD that often requires aggressive resuscitation and premature termination of HD. It is widely accepted that many factors influence HD-related hypotension [5].Nitric oxide (NO) is an endogenous vasodilator and an increase in NO synthesis is known to decrease the blood pressure [8,14]. There are some reports suggesting that NO may contribute to HD-related hypotension. It has been shown that there is a correlation between the increase in levels of plasma nitrates and nitrites (NOx) and the reduction in blood pressure in HD patients [12,15]. Methylene blue, a NO inhibitor, prevented hypotension in a few patients undergoing HD therapy [18], but it was conceivable that basic examination concerning an involvement of NO in HDrelated hypotension was insufficient. Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are powerful inducers of the inducible form of NO synthase (iNOS) [6], which causes overproduction of NO [19], and activate constitutive endothelial NO synthase (eNOS) [3]. Plasma levels of these cytokines chronically increase in renal disease patients undergoing HD therapy [6]. The cause may be partly attributable to decreased renal clearance [20]. These results suggest that the ability to produce NO in renal dysfunction is greater than that in normal renal function.Therefore, the present study was devised to establish an experimental renal dysfunctional dog model and to compare this model with a normal animal as to the change in blood pressure in the case of HD. Furthermore, we studied the relationship of NO to HD-related hypotension in this model by measuri...

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