This Article Abstract Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, X. C. Articles by Johns, E. J. Search for Related Content PubMed PubMed Citation Articles by Wu, X. C. Articles by Johns, E. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE SODIUM Related Collections Animal models of human disease Other hypertension Autonomic, reflex, and neurohumoral control of circulation Oxidant stress

(Hypertension. 2002;39:790.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Nitric Oxide Modulation of Neurally Induced Proximal Tubular Fluid Reabsorption in the Rat

Xiao Chun Wu; Edward J. Johns

From the Department of Physiology, The Medical School, Birmingham, United Kingdom.

Correspondence to Edward J. Johns, Department of Physiology, University College Cork, Cork, Ireland. E-mail e.j.johns{at}ucc.ie

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
This study investigated the role of NO in mediating the renal sympathetic nerve–mediated increases in proximal tubular fluid reabsorption (Jva). In inactin-anesthetized Wistar rats, renal sympathetic nerve stimulation (15 V, 2 ms) at 0.75 and 1.0 Hz did not change blood pressure or glomerular filtration rate but did decrease urine flow and sodium excretion in a frequency-related fashion by 40% to 50% at 1.0 Hz (both, P<0.01). Renal nerve stimulation in control animals increased Jva by 11% at 0.75 Hz (P<0.05) and 31% at 1.0 Hz (P<0.01). Intraluminal N-nitro-L-arginine methyl ester (L-NAME) resulted in a higher basal Jva (19%, P<0.05), and renal nerve stimulation had no effect on Jva. When L-NAME plus sodium nitroprusside was present intraluminally, however, there were frequency-dependent increases in Jva that were similar in pattern and magnitude to the control rats. Introduction of the relatively selective nNOS blocker 7-nitroindazole intraluminally, at 10^-6 and 10^-4 M, raised basal Jva by 18% and 24%, respectively (P<0.01), and renal nerve stimulation did not change Jva. Intraluminal aminoguanidine (10^-4 M), a relatively selective iNOS blocker, did not affect basal Jva, which remained unchanged during renal nerve stimulation. These data are consistent with NO exerting a tonic inhibitory action on the basal levels of Jva, which, in part, is caused by NO generated by the nNOS isoform. Moreover, the findings have revealed that the presence of NO is necessary to ensure that renal nerves can stimulate fluid reabsorption by the proximal tubules, requiring NO generated from both nNOS and iNOS.

Key Words: nitric oxide • renal nerves • antinatriuresis • sodium • kidney

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
The renal sympathetic nerves play an important role in regulating renin release, tubular sodium and water reabsorption, and renal vascular resistance. Increasing levels of renal nerve activity progressively recruit these functions; that is, at low frequencies there is renin release. Thereafter, increased tubular reabsorption of fluid becomes apparent, and it is only at the higher frequencies that there are reductions in renal blood flow and glomerular filtration rate.^1,2 Noradrenaline is released from the renal sympathetic nerve endings and, as at other sympathetic neuroeffector junctions, has an autoinhibitory feedback action, mediated via presynaptic ₂-adrenoceptors, to attenuate the level of neurotransmitter release.³ At the postsynaptic level, noradrenaline acts on the ₁-adrenoceptors of the epithelial cells to stimulate sodium, and hence water, transport by activation of the Na⁺/K⁺-ATPase at the basolateral membrane and the Na⁺/H⁺-exchanger at the apical membrane.^4,5

Recently, there has been increasing interest in the role of NO in the control of renal function. NO synthase (NOS) catalyzes the generation of NO, which stimulates cyclic GMP production to modify specific aspects of renal function.⁶ At least 3 isoforms of NOS have been identified so far: inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS), all of which are present within the kidney to varying degrees. Thus, with regard to the cortex, the endothelial cells of peritubular capillaries, macula densa, and proximal tubular cells all demonstrate NOS mRNA and NOS immunoreactivity in perivascular nerve fibers, but the functional role of NO on proximal tubular function is unclear. Endothelial cell–derived NO or infusion of cGMP into perfused proximal tubules has been reported to stimulate the Na⁺/H⁺-exchanger,⁷ which would lead to increased fluid reabsorption. Moreover, micropuncture studies have shown N^G-monomethyl-L-arginine (L-NMMA), a nonselective NOS blocker, to cause a reduction in proximal fluid reabsorption in control and sham-operated rats, but this effect was reported to be abolished by renal denervation.⁸ These observations would indicate that the action of NO required the participation of the renal sympathetic nerves. In contrast, it has been shown previously that intratubular administration of sodium nitroprusside (SNP) depressed basal proximal tubular fluid reabsorption, whereas it was increased by N-nitro-L-arginine methyl ester (L-NAME) in anesthetized Sprague Dawley and Wistar rats.^9,10 Together, these observations imply that the final action of NO may be variable because of its action on different components of the reabsorptive processes, ie, either on the Na⁺/K⁺-ATPase or the Na⁺/H⁺-exchanger at basal levels, or when these exchangers are stimulated. Our earlier report also demonstrated that the action of NO on proximal tubular fluid reabsorption (Jva) was renal sympathetic nerve–dependent and also that the active enzyme was likely to be nNOS because administration of the relatively selective nNOS inhibitor, 7-nitroindazole (7-NI), also increased basal Jva. However, the location of this nNOS was uncertain, although the nitrergic nerve fibers found in the kidney may be one of the important anatomical locations.¹¹

The aim of this study was to examine the potential influence of NO on the increased proximal tubular fluid reabsorption resulting from low level renal nerve stimulation and to elucidate which isoforms of NOS might be involved. This was performed by measuring the changes in proximal tubular fluid reabsorption in response to renal nerve stimulation following blockade of NOS using nonselective (L-NAME) and selective (7-NI and aminoguanidine) NOS inhibitors, as well as an NO donor (SNP) alone and together with L-NAME.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Experiments were performed under the UK project license PPL 40/1367 and the personal investigator licenses PIL 40/00371 and 40/03881 to E.J. Johns and X.C. Wu. Male Wistar rats (240±30 g) were food restricted the night before use and given free access to water. The inactin-anesthetized (100 mg/kg IP) animals were maintained at 36°C to 36.5°C. Cannulae were placed in the right femoral vein for infusion of saline (150 mmol/L NaCl) and inulin, in the femoral artery for monitoring blood pressure, and in the bladder for urine drainage. The left kidney was exposed and placed in a kidney cup, and its ureter was cannulated.¹⁰ The renal sympathetic nerves were dissected out, sealed onto stimulating electrodes, and connected to a Grass S8 stimulator.¹⁰ Thereafter, a 2-mL bolus of inulin (15% in saline) was given intravenously plus an infusion of 1.6 mL · h^-1 · 100 g body weight^-1, and experiments began 1 hour later.

The micropuncture procedure was as described previously. Briefly, superficial proximal tubules were punctured, and a column of Sudan black–stained castor oil was injected and then split by a small volume of test solution. Images of the shrinking split-drop were captured using a microcomputer, which stored and analyzed the images.¹² Proximal tubular fluid uptake per unit surface area of epithelium (Jvax10^-4 mm³ · mm^-2 · s^-1) was determined 2 to 3 times in each of the tubules, and the mean values were taken.

Clearance periods of 15 minutes were collected, and the plasma and urine samples were assayed for inulin and electrolytes.¹⁰ Groups of rats were given intratubular infusions of (1) artificial proximal tubular fluid (APTF), (2) APTF plus L-NAME (10^-4 M), (3) APTF plus 7-NI (10^-4 M), (4) 7-NI (10^-6 M), (5) APTF plus aminoguanidine (10^-4 M), and (6) APTF plus L-NAME (10^-4 M) plus SNP (10^-4 M).

At least one pair of surface nephrons per rat was used. Jva was measured under basal conditions and then during renal sympathetic nerve stimulation at 0.75 or 1 Hz (2 ms, 15 V), in random order. After a 15-minute recovery period, a second set of measurements was performed using a different nephron. The drugs were presented randomly to the tubules in either the first or second set of measurements. After the Jva measurements, 15-minute urine collections were started for whole kidney function. Inactin, 7-NI, and aminoguanidine were obtained from Research Biochemicals International. L-NAME, SNP, and castor oil were obtained from Sigma; all other compounds were obtained from BDH.

Data were calculated as mean±SEM. Differences within groups were analyzed using the paired Student’s t test; between groups, using a 1-way ANOVA. Significance was taken at the 5% level.

An expanded Methods section can be found in an online data supplement available at http://www.hypertensionaha.org.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Electrical stimulation of the renal sympathetic nerves at both 0.75 and 1.0 Hz had no effect on blood pressure (98±1 mm Hg) or glomerular filtration rate, which remained stable over the experimental periods (Table). Urine flow was reduced progressively when the nerves were stimulated, by 28% at 0.75 Hz (P<0.05) and 39% at 1 Hz (P<0.01), compared with basal values. Sodium excretion was also reduced during renal nerve stimulation, by 29% at 0.75 Hz (P<0.05) and 49% at 1 Hz (P<0.01), compared with basal levels.

View this table: [in this window] [in a new window]   Table 1. Blood Pressure and Whole Kidney Glomerular Filtration Rate, Urine Flow, and Sodium Excretion During Renal Nerve Stimulation in Wistar Rats

Administration of L-NAME intraluminally (Figure 1) increased basal Jva by 19% compared with that measured when APTF was given alone (3.27±0.20x10^-4 versus 2.67±0.10x 10^-4 mm³ · mm^-2 · s^-1, P<0.05), whereas coadministration of L-NAME plus SNP caused only a small reduction in basal levels of proximal tubular fluid reabsorption (Figure 1). 7-NI given into the tubules at 10^-6 and 10^-4 M (Figure 2) increased basal Jva by 18% and 27%, respectively (P<0.01 and P<0.001), from 2.52±0.10x10^-4 to 2.99±0.12x10^-4 mm³ · mm^-2 · s^-1 and from 2.4±0.07x10^-4 to 3.05±0.08x10^-4 mm³ · mm^-2 · s^-1, respectively. By contrast, intraluminal aminoguanidine (Figure 2) had no effect on basal levels of proximal tubular fluid reabsorption, which were the same as those obtained when APTF was present in the tubules.

View larger version (39K): [in this window] [in a new window]   Figure 1. This illustrates the effect of renal nerve stimulation on Jva under basal conditions (open bars) and when the renal sympathetic nerves were stimulated at 0.75 Hz (stippled bars) and at 1.0 Hz (slashed bars). APTF present in the tubules (control), L-NAME 10-4 M present intraluminally (L-NAMEx10-4), and L-NAME and SNP present in the tubules (L-NAME & SNPx10-4). *P<0.05 vs basal, and P<0.05 vs basal control, with the basal in the presence of L-NAME or L-NAME & SNP.

View larger version (42K): [in this window] [in a new window]   Figure 2. This demonstrates the influence of intraluminal 7-NI at 10-6 M (7-NIx10-6 M), 7-NI at 10-4 M (7-NIx10-4 M), and aminoguanidine (aminoguanidinex10-4) on basal Jva (open bars) and demonstrates the responses to renal nerve stimulation at 0.75 Hz (stippled bars) and 1.0 Hz (slashed bars). P<0.05 vs basal values, with APTF against 7-NI or aminoguanidine.

Stimulation of the renal sympathetic nerves when APTF was present in the tubules increased proximal tubular fluid reabsorption by 11% at 0.75 Hz (P<0.05) and 31% at 1 Hz (P<0.01, Figure 1). However, when L-NAME was present intraluminally, renal nerve stimulation at both frequencies failed to change tubular fluid reabsorption (Figure 1), which remained at an elevated level. When L-NAME plus SNP was given intraluminally, the increases in tubular fluid reabsorption in response to renal nerve stimulation were 15% at 0.75 Hz and 35% at 1.0 Hz, which were similar in pattern and magnitude to those observed when APTF only was present in the tubules (Figure 1). During intratubular administration of 7-NI 10^-6 M, renal nerve stimulation had no effect on proximal reabsorption (Figure 2). However, in the presence of 7 NI 10^-4 M, renal nerve stimulation at 0.75 Hz increased proximal tubular fluid reabsorption by 9% but was lower by 11% at 1.0 Hz compared with basal values, although these changes were not statistically significant. When aminoguanidine was present intraluminally, stimulation of the renal nerves was unable to change proximal tubular fluid reabsorption (Figure 2).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
It was important to establish that the low level of renal nerve stimulation had minimal effects on renal hemodynamics. Indeed, neither stimulation frequency altered blood pressure or whole kidney glomerular filtration rate at a time when there were frequency-related decreases in urine flow and sodium excretion. The same stimulation parameters caused frequency-dependent increases in Jva, which was indicative of the renal nerves acting directly on the fluid reabsorptive processes of the proximal epithelial cells, compatible with earlier micropuncture studies.^13,14

NO is involved in determining sympathetic outflow¹⁵ and modulating neuroeffector junction efficiency.¹⁶ At the kidney, Barajas et al¹¹ demonstrated diaphorase-staining nerve fibers and somata to be present, which is consistent with nitrergic neurones, and they frequently colocalized with the sympathetic innervation of the kidney. The exact mechanism by which the nitrergic and adrenergic nerves might interact at the neuroeffector junction is still not resolved. Yamamoto et al¹⁷ found that field stimulation of rat mesenteric arteries caused noradrenaline release, which was decreased by some 50% in the presence of N-nitro-L-arginine (30 µmol/L), suggesting NO was necessary for effective neurotransmission. Conversely, Egi et al¹⁸ and Maekawa et al,¹⁹ using the dog, found that intrarenal blockade of NO generation was associated with an increase, whereas NO donors led to a suppression of noradrenaline spillover from the kidney. Despite these diverse reports, there is a view that NO released from the nerve terminals can act presynaptically to exert a tonic inhibitory action on transmitter release.

We reported previously¹⁰ that intratubular administration of the NOS blocker L-NAME increased proximal tubular fluid reabsorption, compatible with NO exerting a tonic inhibitory action on basal epithelial cell transport processes. Moreover, this appeared to be dependent on the nNOS isoform, as proximal reabsorption was also increased after the relatively selective nNOS blocker 7-NI but not after aminoguanidine, the relatively selective iNOS blocker. This concept was reinforced by the observations that application of a NO donor to the epithelial cells caused Jva to decrease^9,10 and the present study showing fluid reabsorption to be increased by L-NAME and 7-NI. Interestingly, in our previous report,¹⁰ the tonic inhibitory action of NO was prevented by renal denervation, suggesting an interaction between NO and noradrenergic stimulation of proximal fluid reabsorption. Two possible mechanisms can be considered. First, there might be a tonic inhibitory action of NO only on that component of epithelial cell transport processes determined by the renal nerves. Second, the NOS blockers might be diffusing further through the epithelial cells to the varicosities of the sympathetic fibers to modulate transmission at the neuroeffector junction. To further investigate this interaction, the converse approach was taken of directly stimulating the renal sympathetic nerves.

Low-level renal nerve stimulation increased proximal fluid reabsorption in a frequency related manner, which was effectively blocked by intraluminal administration of L-NAME. This suggested that the presence of NO was essential for the renal nerves to increase fluid transport by the epithelial cells. This was supported by the observation that the concomitant administration of L-NAME plus the NO donor SNP restored the ability of the renal nerves to increase tubular fluid reabsorption. This effect of NO appeared to be mediated, in part, by NO generated by the nNOS isoform as not only were basal levels of Jva increased by both low and high doses of 7-NI, but also the neurally induced increases in Jva were prevented by the compound.

The relatively selective iNOS blocker, aminoguanidine, also prevented the neurally induced rise in Jva but had no effect on basal levels. These observations might suggest that NO derived from iNOS was involved in mediating part of the neurally stimulated Jva, although there may be some question as to the selectivity of the compound at this concentration.²⁰ There is evidence that iNOS is expressed constitutively at low levels in the kidney and may generate NO, which contributes to the neural stimulation of Jva. Surprisingly, these observations indicate a further mechanism by which NO might modulate the ability of noradrenaline to increase epithelial cell transport processes; ie, NO was in some way facilitating specifically the renal nerve–stimulated fluid reabsorption via the neurotransmitter noradrenaline. Exactly how NO might exert these differing actions—one by inhibiting basal levels of fluid reabsorption, the other by facilitating neurally stimulated fluid reabsorption—is unclear. However, fluid transport at the proximal tubular epithelial cells is determined by a number of factors, eg, angiotensin II,²¹ and there are reports that NO is necessary to allow the full impact of angiotensin II on the transport processes.²² Moreover, low concentrations of NO donors given intraluminally stimulate tubular reabsorptive processes²³ and sodium uptake by isolated brush border vesicles,²⁴ whereas high intraluminal levels decrease fluid reabsorption.^9,10 Indeed, the role of NO is not clear and may exert both inhibitory and facilitatory roles on basal and stimulated fluid transport. This lack of understanding of how NO influences transport processes in the proximal tubule has been commented upon recently by Liang and Knox,²⁵ who proposed that NO could have both facilitatory actions on the Na⁺/H⁺-exchanger and inhibitory actions on the Na⁺/H⁺-exchanger and Na⁺/K⁺-ATPase depending on whether studies were performed under basal or stimulated conditions. Thus, in the present studies, the NO may be regulating basal and adrenergically stimulated fluid reabsorption at different levels utilizing differing intracellular pathways.

Received June 18, 2001; first decision July 19, 2001; accepted November 11, 2001.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. DiBona GF. Neural control of the kidney: functionally specific renal sympathetic nerve fibres. Am J Physiol. 2000; 279: R1517–R1524.

2. DiBona GF, Kopp UC. Neural control of kidney function. Physiol Rev. 1997; 77: 175–197.

3. Langer SZ. Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol. 1977; 60: 481–498.[Medline] [Order article via Infotrieve]

4. Aperia A, Ibarra F, Svensson LB, Klee C, Greengard P. Calcineurin mediates a adrenergic stimulation of Na⁺-K⁺ ATPase activity in renal tubule cells. Proc Natl Acad Sci U S A. 1992; 89: 7394–7397.[Abstract/Free Full Text]

5. Nord EP, Howard MJ, Hafezi A, Moradeshagi P, Vaystub S, Insel P. ₂-Adrenergic agonists stimulate Na-H antiport activity in rabbit proximal tubule. J Clin Invest. 1987; 80: 1755–1762.[Medline] [Order article via Infotrieve]

6. Kone BC, Baylis C. Biosynthesis and homeostatic roles of nitric oxide in the normal kidney. Am J Physiol. 1997; 272: F561–F578.[Medline] [Order article via Infotrieve]

7. Amorena C, Castro AF. Control of proximal tubule acidification by the endothelium of the peritubular capillaries. Am J Physiol. 1997; 272: R691–R694.[Medline] [Order article via Infotrieve]

8. Gabbai FB, Thomson SC, Peterson LW, Malvey K, Blantz RC. Glomerular and tubular interactions between renal adrenergic activity and nitric oxide. Am J Physiol. 1995; 268: F1004–F1008.[Medline] [Order article via Infotrieve]

9. Eitle E, Hiranyachattada S, Wang H, Harris PJ. Inhibition of proximal tubular fluid reabsorption by nitric oxide and atrial natriuretic peptide in rat kidney. Am J Physiol. 1998; 274: C1075–C1080.[Medline] [Order article via Infotrieve]

10. Wu XC, Harris PJ, Johns EJ. Nitric oxide and renal nerve–mediated proximal tubular reabsorption in normotensive and hypertensive rats. Am J Physiol. 1999; 277: F560–F566.[Medline] [Order article via Infotrieve]

11. Liu L, Liu GL, Barajas L. Distribution of nitric oxide synthase–containing ganglionic neuronal somata and postganglionic fibers in the rat kidney. J Comp Neurol. 1996; 369: 16–30.[CrossRef][Medline] [Order article via Infotrieve]

12. Harris PJ, Cullman M, Thomas D, Morgan TO. Digital image capture and analyses for split-droplet micropuncture. Pflug Arch. 1987; 408: 615–618.[CrossRef][Medline] [Order article via Infotrieve]

13. Bello-Reuss E, Trevino DL, Gothschalk CW. Effect of renal sympathetic nerve stimulation on proximal water and sodium reabsorption. J Clin Invest. 1976; 57: 1104–1107.[Medline] [Order article via Infotrieve]

14. Goransson A, Ulfendahl HR. Increase in proximal tubular fluid liquid reabsorption by renal nerve stimulation: a split oil droplet study. Acta Physiol Scand. 1988; 133: 455–458.[Medline] [Order article via Infotrieve]

15. Zhang K, Mayhan WG, Patel K. Nitric oxide within the paraventricular nucleus mediates changes in renal sympathetic nerve activity. Am J Physiol. 1997; 273: R864–R872.[Medline] [Order article via Infotrieve]

16. Garthwaite J, Boulton CL. Nitric oxide signaling in the central nervous system. Am Rev Physiol. 1995; 57: 683–706.[CrossRef][Medline] [Order article via Infotrieve]

17. Yamamoto R, Wada A, Asada Y, Yanagita T, Yuhi T, Nuna H, Sumiyoshi A, Kobayashi H, Lee TJF. Nitric oxide–dependent and –independent norepinephrine release in rat mesenteric arteries. Am J Physiol. 1997; 272: H207–H210.[Medline] [Order article via Infotrieve]

18. Egi Y, Matsumura Y, Murata S, Umekawa T, Hisaki K, Takaoka M, Morimoto S. Effect of N^G-nitro-L-arginine, a nitric oxide synthase inhibitor, on norepinephrine overflow and antidiuresis induced by stimulation of renal nerves in anesthetized dogs. J Pharmacol Exp Ther. 1994; 269: 529–535.[Abstract/Free Full Text]

19. Maekawa H, Matsumura Y, Matsuo G, Morimoto S. Effect of sodium nitroprusside on norepinephrine overflow and antidiuresis induced by stimulation of the renal nerves in anesthetized dogs. J Cardiovasc Pharmacol. 1996; 27: 211–217.[CrossRef][Medline] [Order article via Infotrieve]

20. Misko PC, Moore WM, Kasten TP, Nickols AG, Corbett JA, Tilton RG, McDaniel ML, Williamson J, R, Currie MG. Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eu J Pharmacol. 1993; 233: 119–125.[CrossRef][Medline] [Order article via Infotrieve]

21. Navar LG, Imig JD, Zou L, Wang CT. Intrarenal production of angiotensin II. Semin Nephrol. 1997; 17: 412–422.[Medline] [Order article via Infotrieve]

22. Nicola LD, Blantz RC, Gabbai FB. Nitric oxide and angiotensin II. J Clin Invest. 1992; 89: 1248–1256.[Medline] [Order article via Infotrieve]

23. Wang T. Nitric oxide regulates HCO-₃ and Na⁺ transport by a cGMP-mediated mechanism in the kidney proximal tubule. Am J Physiol. 1997; 272: F242–F248.[Medline] [Order article via Infotrieve]

24. Green M, Ruiz OS, Kear F, Arruda JA. Dual effect of cyclic GMP on brush border Na⁺/H⁺ antiporter. Proc Soc Exp Biol Med. 1991; 198: 846–851.[CrossRef][Medline] [Order article via Infotrieve]

25. Liang M, Knox FG. Production and functional roles of nitric oxide in the proximal tubule. Am J Physiol. 2000; 278: R117–R1124.

This article has been cited by other articles:

				L. M. Yamaleyeva, P. E. Gallagher, S. Vinsant, and M. C. Chappell Discoordinate regulation of renal nitric oxide synthase isoforms in ovariectomized mRen2.Lewis rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R819 - R826. [Abstract] [Full Text] [PDF]

				N. M. Bagnall, P. C. Dent, A. Walkowska, J. Sadowski, and E. J. Johns Nitric oxide inhibition and the impact on renal nerve-mediated antinatriuresis and antidiuresis in the anaesthetized rat J. Physiol., December 15, 2005; 569(3): 849 - 856. [Abstract] [Full Text] [PDF]

				K. M. McCormick, E. M. Bravo, and C. T. Kappagoda Role of adrenergic receptors in the reflex diuresis in rabbits during pulmonary lymphatic obstruction Exp Physiol, May 1, 2005; 90(3): 341 - 347. [Abstract] [Full Text] [PDF]

				K. M. McCormick, S. Gunawardena, K. Ravi, E. M. Bravo, and C. T. Kappagoda Role of nitric oxide in the reflex diuresis in rabbits during pulmonary lymphatic obstruction Exp Physiol, July 1, 2004; 89(4): 487 - 496. [Abstract] [Full Text] [PDF]

				X. C. Wu and E. J. Johns Interactions between nitric oxide and superoxide on the neural regulation of proximal fluid reabsorption in hypertensive rats Exp Physiol, May 1, 2004; 89(3): 255 - 261. [Abstract] [Full Text] [PDF]

				M. Graebe, L. Brond, S. Christensen, S. Nielsen, N. V. Olsen, and T. E. N. Jonassen Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats Am J Physiol Renal Physiol, February 1, 2004; 286(2): F288 - F297. [Abstract] [Full Text] [PDF]

				P. A. Ortiz and J. L. Garvin Cardiovascular and renal control in NOS-deficient mouse models Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R628 - R638. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, X. C. Articles by Johns, E. J. Search for Related Content PubMed PubMed Citation Articles by Wu, X. C. Articles by Johns, E. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE SODIUM Related Collections Animal models of human disease Other hypertension Autonomic, reflex, and neurohumoral control of circulation Oxidant stress