Mechanism underlying diuretic effect of L-NAME at a subpressor dose. Am J Physiol Renal Physiol 2001 Sep;281(3):F414-9
Date
08/15/2001Pubmed ID
11502590DOI
10.1152/ajprenal.2001.281.3.F414Scopus ID
2-s2.0-0034826998 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
The diuretic effects of nitric oxide (NO) synthase inhibitors administered at subpressor dose in rats are controversial, and the tubular segments involved are not known. In the present study, we examined the effect of N(omega)-nitro-L-arginine methyl ester (L-NAME) at a subpressor dose on renal interstitial NO and cGMP activity and on renal tubular segmental reabsorption of fluid in the rat. Intravenous infusion of L-NAME at 1 microg. kg(-1). min(-1) in Sprague-Dawley rats (N = 8), which did not alter mean arterial pressure or glomerular filtration rate, significantly increased urine flow rate (U(v); from 78.2 +/- 12.7 to 117.1 +/- 14.9 microl/min, P < 0.05). Paradoxically, this effect of L-NAME was concomitant with significant increases in nitrite/nitrate (from 10.79 +/- 1.20 to 16.50 +/- 2.60 microM, P < 0.05) and cGMP (from 0.65 +/- 0.09 to 0.98 +/- 0.18 nM, P < 0.05) concentrations in renal cortical microdialysate as well as the nitrite/nitrate concentration in the medullary microdialysate. Micropuncture studies in the superficial nephron revealed that L-NAME significantly increased the flow rate (from 8.3 +/- 0.9 to 12.2 +/- 1.2 nl/min, P < 0.05) and fractional delivery of fluid to the distal tubule, but not those in the late proximal tubule. In conclusion, L-NAME, at the subpressor dose used in this study, increased renal nitrate/nitrite and cGMP and inhibited fluid reabsorption in tubular segments between the late proximal tubule and the distal tubule of superficial nephrons.
Author List
Liang M, Berndt TJ, Knox FGMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Cyclic GMP
Diuresis
Diuretics
Glomerular Filtration Rate
In Vitro Techniques
Infusions, Intravenous
Jugular Veins
Kidney
Kidney Cortex
Kidney Medulla
Kidney Tubules, Distal
Kidney Tubules, Proximal
Male
Microdialysis
NG-Nitroarginine Methyl Ester
Natriuresis
Nitric Oxide
Nitric Oxide Synthase
Rats
Rats, Sprague-Dawley
Sodium