Short communicationA nitric oxide donor NOC 7 suppresses renal responses induced by norepinephrine and angiotensin II in the NO-depleted denevated rabbit kidney
Introduction
Nitric oxide (NO) has been suggested to contribute to maintaining renal circulation and urine formation and modulate neural and humoral control of the renal functions. NO synthase inhibitors such as N-monomethyl-l-arginine, NG-nitro-l-arginine or Nω-nitro-l-arginine methyl ester (l-NAME) induce renal vasoconstriction and antinatriuresis (Baylis et al., 1990; Tolins et al., 1990; Majid et al., 1993) and facilitate norepinephrine- and angiotensin II-induced renal vasoconstriction and antinatriuresis (Ohishi et al., 1992; Matsumura et al., 1995; Adachi et al., 1996) in experimental animals. Parakh et al. (1996)reported that an authentic NO donor sodium nitroprusside attenuated a reduction in renal blood flow induced by intrarenal arterial infusion of norepinephrine and angiotensin II in the absence or presence of l-NAME in anesthetized rats, confirming the counteracting effects of NO on the vasoconstrictor stimuli in vivo. However, it was unclear whether the elevation of NO level induced by NO donors affects the agonist-induced changes in urine formation.
We have recently demonstrated that a novel NO donor 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC 7; Hrabie et al., 1993) attenuated norepinephrine- and angiotensin II-induced antinatriuresis which may be due mainly to enhanced tubular Na+ reabsorption and reduced glomerular filtration, respectively, in the absence of l-NAME in anesthetized rabbits (Adachi et al., 1997). Unlike sodium nitroprusside, NOC 7 spontaneously releases NO in biological fluid and dose not produce toxic products such as cyanide (Hrabie et al., 1993) and is considered to be useful as a short-acting nitrovasodilator that has no major adverse effect or tolerance (Zhang et al., 1996).
Our previous study, however, suggested that the angiotensin II-induced antinatriuresis involves enhanced tubular Na+ reabsorption in the presence of l-NAME (Adachi et al., 1996). Thus, endogenously formed NO may alter contribution of the renal filtration and reabsorption components to agonist-induced antinatriuretic responses.
In the present study, to clarify further the counteracting effect of NO on the agonist-induced antinatriuresis, we examined whether NOC 7 can suppress the norepinephrine- and angiotensin II-induced renal responses in the presence of l-NAME in anesthetized rabbits.
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Preparation
Male Japanese white rabbits (2.5–3.5 kg) were anesthetized with sodium pentobarbital (40 mg/kg) injected through a marginal ear vein. The trachea was cannulated and the rabbit was artificially ventilated with room air (stroke volume 50 ml, 25 rpm). A double lumen catheter was inserted into the right femoral vein for drug administration. Anesthesia was maintained by continuous infusion of pentobarbital (2–4 mg/kg per h, i.v.) throughout the experiments. Inulin, dissolved in plasma extender
Results
In the control period of non-pretreated rabbits (group 1), intrarenal arterial infusion of norepinephrine reduced renal blood flow, urine flow rate, urinary Na+ excretion and fractional Na+ excretion (Table 1). After the norepinephrine infusion was stopped, each value returned nearly to its basal level (data not shown). Intrarenal arterial infusion of l-NAME reduced renal blood flow, urine flow rate, urinary Na+ excretion and fractional Na+ excretion with little change in glomerular filtration
Discussion
We have recently reported that a spontaneous NO donor NOC 7 attenuated antinatriuresis induced by norepinephrine and angiotensin II in anesthetized rabbits (Adachi et al., 1997). However, it is still unclear whether NOC 7 affects norepinephrine-induced hypofiltration or angiotensin II-evoked tubular reabsorption, because the influence of norepinephrine on filtration function was very small and the possible tubular action of angiotensin II was not observed in our study (Adachi et al., 1997). We
Acknowledgements
This work was supported by The Research Foundation for Pharmaceutical Sciences, Japan (to H.H.).
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