HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) All Versions of this Article: 290/2/H772    most recent 00242.2005v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Nishiyama, A. Articles by Navar, L. G. Search for Related Content PubMed PubMed Citation Articles by Nishiyama, A. Articles by Navar, L. G.

Renal interstitial fluid ATP responses to arterial pressure and tubuloglomerular feedback activation during calcium channel blockade

¹Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana; and ²Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan

Submitted 14 March 2005 ; accepted in final form 30 September 2005

	ABSTRACT

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION GRANTS REFERENCES

 
A close relationship between changes in renal interstitial fluid (RIF) ATP concentrations and renal autoregulatory or tubuloglomerular feedback (TGF)-dependent changes in renal vascular resistance (RVR) has been demonstrated, but it has not been determined whether the changes in RIF ATP are a consequence or the cause of the changes in RVR. The present study was performed in anesthetized dogs to assess the changes in RIF ATP following changes in renal arterial pressure (RAP) or stimulation of the TGF mechanism under conditions where changes in RVR were prevented by nifedipine, a calcium channel blocker. RIF ATP levels were measured by using microdialysis probes. Intra-arterial infusion of nifedipine (0.36 µg·kg^–1·min^–1) increased renal blood flow (RBF: from 4.49 ± 0.27 to 5.34 ± 0.39 ml·min^–1·g^–1) and glomerular filtration rate (GFR: from 0.84 ± 0.07 to 1.09 ± 0.11 ml·min^–1·g^–1). Under conditions of nifedipine infusion, autoregulatory adjustments in RBF, GFR, and RVR were not observed during stepwise reductions in RAP within the autoregulatory range (from 135 ± 7 to 76 ± 1 mmHg, n = 7). Furthermore, stimulation of the TGF mechanism with intra-arterial infusion of acetazolamide (100 µg·kg^–1·min^–1) did not alter RBF, GFR, and RVR (n = 7). During treatment with nifedipine, RIF ATP levels were significantly decreased in response to reductions in RAP (10.7 ± 0.7, 5.8 ± 0.7 and 2.8 ± 0.3 nmol/l at 135 ± 7, 101 ± 4, and 76 ± 1 mmHg, n = 7) and increased by acetazolamide infusion (from 8.8 ± 0.8 to 17.0 ± 1.8 nmol/l, n = 7). These results are similar to those that occurred in dogs not treated with nifedipine and thus demonstrate that the changes in RIF ATP can occur in the absence of autoregulatory or TGF-mediated changes in RVR. The data provide further support to the hypothesis that RIF ATP contributes to adjustments in RVR associated with renal autoregulation and changes in activity of the TGF mechanism.

tubuloglomerular feedback mechanism; renal autoregulation; nifedipine; acetazolamide; renal microdialysis; purine nucleotides

The preglomerular renal vasculature expresses abundant P2X₁ receptors, whereas efferent arterioles appear to be devoid of such receptors (5). Furthermore, ATP administration from the interstitial side exerts direct vasoconstrictor actions on afferent, but not efferent, arterioles (11, 12, 35). ATP activates voltage-dependent Ca²⁺ influx pathways in freshly isolated vascular smooth muscle cells obtained from preglomerular microvessels, and these actions of ATP are sensitive to blockade of L-type calcium channels (11, 33). Stopflow pressure feedback responses to increases in late proximal perfusion rate are markedly blunted during peritubular capillary infusion with saturating doses of ATP (17). Similarly, intrarenal arterial infusion of high doses with ATP resulted in marked impairment of renal blood flow (RBF) and glomerular filtration rate (GFR) autoregulatory efficiency (16). Studies using the juxtamedullary preparation showed that P2X receptor desensitization, saturation, or blockade markedly attenuates afferent arteriolar autoregulatory responses to increases in renal perfusion pressure (11–13). Inscho et al. (12) showed that elimination of TGF responses by papillectomy markedly attenuated pressure-mediated afferent arteriolar vasoconstriction in wild-type mice but had no effect on afferent diameter in P2X₁ knockout mice, which behaved as though TGF was absent before papillectomy.

Studies using microdialysis probes demonstrated that renal interstitial fluid (RIF) ATP levels are closely associated with autoregulatory changes in renal vascular resistance (RVR) during stepwise reductions in renal arterial pressure (RAP) (21, 22). Further studies showed that whole kidney stimulation of the TGF mechanism elicited by administration of a carbonic anhydrase inhibitor acetazolamide to inhibit proximal reabsorption rate and increase distal volume delivery (26) results in increases in RIF ATP concentrations (21, 22). In contrast, inhibition of the TGF signaling mechanism with furosemide treatment reduced the RIF ATP concentrations. In addition, the relationship between autoregulatory changes in RVR and RIF ATP concentrations was enhanced following treatment with acetazolamide, whereas furosemide abolished this relationship (22). Collectively, these data demonstrate that RIF ATP concentrations change in association with the changes in RVR in a manner consistent with the hypothesis that RIF ATP mediates the autoregulatory and TGF-dependent changes in RVR. However, the sequence of events has not been delineated in these previous experiments. Because it has also been clearly shown that mechanical stimuli such as shear stress and stretch directly induce ATP release from various cells, including vascular smooth muscle cells (25), it is also possible that the changes in RIF ATP concentrations are the consequence of, rather than the cause of, the changes in RVR.

Accordingly, it seemed imperative to determine whether the changes in RIF ATP occur in response to the changes in RVR or can occur independently of the RVR changes. This study was performed to test the hypothesis that changes in RIF ATP concentrations following RAP changes or stimulation of the TGF mechanism occur even under conditions where the changes in RVR are prevented. To accomplish this objective, a calcium channel blocker nifedipine was used to inhibit the autoregulatory and TGF-dependent changes in RVR (18).

	MATERIALS AND METHODS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION GRANTS REFERENCES

 
Animal preparation. Experiments were carried out on mongrel dogs weighing from 15 to 23 kg. The animals were anesthetized with pentobarbital sodium (30 mg/kg iv) and given additional doses as required. The surgical preparation of the animals and basic experimental techniques are identical to those previously described (16, 18, 21, 22). All experimental protocols were approved by the Tulane University and Kagawa University Medical School Animal Care and Use Committee.

Renal microdialysis technique. For the determination of RIF ATP concentrations, we used a microdialysis method (Toyobo, Otsu, Japan) as previously reported (9, 14, 20–22). The microdialysis probes were implanted into the renal cortex and were perfused with Ringer solution (pH = 7.4) at a rate of 3 µl/min. The average in vivo equilibrium rate of ATP was 43 ± 3% (21, 22). The dialysate samples were directly collected from outflow steel tubing of two microdialysis probes and were stored at –70°C before analysis. At the end of each experiment, the kidney was removed and the location of the microdialysis membrane was confirmed by surgical exposure of the probe.

Experimental protocols. At least 90 min before the start of the experimental protocol, the left common carotid artery was partially constricted to elevate the basal level of RAP to above 130 mmHg. This allowed examination of the pressure-flow relationship over a wider range of arterial pressures (16, 18). The experimental protocol was started with RIF and urine collections for two consecutive 10-min periods at spontaneous RAP (n = 14). Nifedipine (Sigma Chemical, St. Louis, MO) was then infused intra-arterially for 90 min at a rate of 0.36 µg·kg^–1·min^–1. After 5 min of initiation of nifedipine infusion, three consecutive 10-min dialysate and urine samples were collected. Subsequently, RAP was reduced by using an adjustable renal arterial clamp within the renal autoregulatory range to around 100 mmHg (step 1) and 75 mmHg (step 2) while continuing the nifedipine infusion in seven dogs. At each level of RAP, 5 min was allowed for stabilization before two 10-min sampling periods were made. In seven other dogs, a continuous infusion of acetazolamide at a rate of 100 µg·kg^–1·min^–1 was added to the nifedipine infusion. The experimental protocols and sample collections performed in this study were identical to those described above. In a separate experimental series, nifedipine (0.36 µg·kg^–1·min^–1) was infused for 90 min to examine the possibility of any time-dependent changes in renal hemodynamics and functions as well as RIF ATP levels (n = 5). Ten-minute dialysate and urine samples were collected at 15, 30, 60, and 90 min after initiation of nifedipine infusion. To minimize nifedipine- and acetazolamide-induced body fluid loss, urine losses were replaced quantitatively with warm (37°C) isotonic saline containing 6 mmol/l KCl infused intravenously, the rate of which was adjusted every 2 min (22). The doses of nifedipine and acetazolamide were determined based on previous studies in dogs (16, 18, 21, 22).

Analytical procedures. ATP concentrations were determined by using the luciferin-luciferase assay (21, 22). Inulin and sodium concentrations in urine and plasma were measured as previously reported (16, 18).

Statistical analysis. The values are presented as means ± SE. Statistical comparisons of the differences were performed using the one-way or the two-way analysis of variance for repeated measures combined with Newman-Keuls post hoc test. P < 0.05 was considered statistically significant.

	RESULTS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION GRANTS REFERENCES

 
Changes in RIF ATP concentrations in response to reductions in RAP during treatment with a calcium channel blocker. Table 1 summarizes the changes in renal hemodynamics, urine flow, and sodium excretion in response to stepwise reductions in RAP during nifedipine infusion (n = 7). Nifedipine alone slightly decreased mean arterial pressure (MAP) and significantly increased RBF and GFR. Control RVR averaged 30.0 ± 0.8 mmHg·ml^–1·min·g and was decreased significantly by nifedipine infusion to 24.1 ± 0.9 mmHg·ml^–1·min·g at 30 min (Fig. 1A). During nifedipine infusion, reductions in RAP within the autoregulatory range led to significant decreases in RBF and GFR at each pressure step (Table 1). However, there were no changes in RVR following reductions in RAP (Fig. 1A), demonstrating an absence of autoregulation. Nifedipine alone significantly increased urine volume (UV) and urinary excretion of sodium (U_NaV). During treatment with nifedipine, UV and U_NaV were significantly decreased in response to reductions in RAP (Table 1).

View larger version (26K): [in this window] [in a new window]   Fig. 1. Changes in renal vascular resistance (RVR: A) and renal interstitial fluid (RIF) ATP concentrations (B) in responses to reductions in renal arterial pressure (RAP) during treatment with nifedipine. RVR values were not altered in responses to stepwise reductions in RAP during nifedipine administration, indicating a loss of autoregulatory efficiency. Pressure-induced changes in RIF ATP concentrations still occurred during treatment with nifedipine. *P < 0.05 vs. control (10 min). P < 0.05 vs. nifedipine (45 min); n = 7 dogs, respectively.

Changes in RIF ATP concentrations in response to the activation of the TGF mechanism during treatment with a calcium channel blocker. Table 2 summarizes effects of acetazolamide on renal hemodynamics, urine flow, and sodium excretion during nifedipine infusion (n = 7). Nifedipine alone slightly decreased MAP and significantly increased RBF, GFR, UV, and U_NaV as described before. Previously, we demonstrated that stimulation of the TGF mechanism by acetazolamide infusion did not alter MAP and RAP but significantly decreased RBF and GFR (21, 22). Treatment with nifedipine prevented the acetazolamide-induced decreases in RBF and GFR, and there were no significant changes in RBF and GFR. Nifedipine infusion alone for 30 min significantly decreased RVR from 30.6 ± 2.8 to 26.7 ± 2.4 mmHg·ml^–1·min·g. During nifedipine infusion, acetazolamide did not alter RVR (26.2 ± 2.2 mmHg·ml^–1·min·g at 30 min, Fig. 2A), indicating that the TGF-mediated RVR changes were prevented by nifedipine. Although nifedipine alone caused almost a twofold increase in U_NaV, acetazolamide infusion during treatment with nifedipine elicited an additional twofold increase in UV on U_NaV (Table 2).

View larger version (21K): [in this window] [in a new window]   Fig. 2. Effects of acetazolamide infusion on RVR (A) and RIF ATP concentrations (B) during treatment with nifedipine. Acetazolamide-induced increases in RVR were not observed during nifedipine administration. However, acetazolamide-induced increases in RIF ATP concentrations still occurred during treatment with nifedipine. *P < 0.05 vs. control (10 min). P < 0.05 vs. nifedipine (45 min); n = 7 dogs, respectively.

Effects of a calcium channel blocker on RIF ATP concentrations. In five other dogs, nifedipine was infused for 90 min. Nifedipine significantly increased RBF, GFR, UV, and U_NaV and decreased RVR (Table 3). These values were unchanged throughout the 90-min infusion of nifedipine. RIF ATP concentrations were not changed during the nifedipine infusion, which remained at similar levels for up to 90 min (Table 3).

	DISCUSSION

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION GRANTS REFERENCES

Early studies showed that macula densa cells have abundant mitochondria but little transport activity as demonstrated by evidence for diminished Na⁺-K⁺-ATPase activity (28), indicating the possibility that the mitochondria present along the basolateral aspects of macula densa cells subserve the role of synthesizing ATP for export as an extracellular signaling molecule. Recently, Bell et al. (2) utilized a biosensor technique and the isolated perfused thick ascending limb of the loop of Henle-macula densa preparation, and they demonstrated that increases in luminal NaCl concentrations sufficient to elicit TGF responses result in the release of ATP from the basolateral surface of macula densa cells. Further studies showed that ATP release from the macula densa cells in response to increases in NaCl concentration was enhanced by dietary salt restriction (15). In the present study, we utilized a microdialysis method and demonstrated that ATP is released into the RIF in response to increases in the activity of the TGF mechanisms caused by treatment with acetazolamide. The results of the present experiments obtained in intact animal experiments do not allow us to address the exact sources of ATP in the dialysate. Nevertheless, these data support the hypothesis based on the previous studies (2, 5, 11–13, 15–17, 19, 21–24, 35), indicating that the changes in RIF ATP concentrations are closely associated with alterations in TGF and renal autoregulatory activities.

Majid et al. (16) examined RBF autoregulatory efficiency in anesthetized dogs during intrarenal infusion of ATP. These authors showed that P2 receptor saturation by infusion of high doses of ATP resulted in decreases in basal RBF and marked impairment of whole kidney autoregulatory efficiency. Interestingly, administration of norepinephrine caused similar reductions in RBF but did not cause any impairment in autoregulatory efficiency of RBF, indicating that the responses to ATP were not simply due to the associated renal vasoconstriction (16). We previously demonstrated that RVR and RIF ATP concentrations decreased consistently in responses to reductions in RAP (21, 22). In the present study, blockade of autoregulatory adjustments in RVR by nifedipine increased basal RBF but did not alter RIF ATP concentrations. However, the pressure-induced reductions in RIF ATP concentrations still occurred during nifedipine infusion, indicating that the changes in RIF ATP concentrations are not the result of changes in RVR.

High renal autoregulatory efficiency is dependent on the integrity of the TGF mechanism as evidenced by the fact that inhibition of the TGF response results in an impairment of autoregulation-associated alterations in RVR (19, 31, 32). In the present study, whole kidney stimulation of the TGF mechanism was elicited by the administration of acetazolamide, a carbonic anhydrase inhibitor, to inhibit proximal reabsorption rate and increase distal solute delivery (26). We previously demonstrated that acetazolamide infusion resulted in decreases in both RBF and GFR, indicating a predominant preglomerular vasocontriction (21, 22). We also observed that acetazolamide consistently increased RVR and RIF ATP concentrations. In addition, inhibition of the TGF response with furosemide prevented acetazolamide-induced increases in RVR and RIF ATP concentrations (21, 22). The results of the present study show that acetazolamide-induced increases in RIF ATP concentrations still occurred during treatment with nifedipine, which prevented the RVR changes. Thus these data indicate that the changes in RIF ATP concentrations are not the consequence of changes in RVR induced by stimulation of the TGF activity and further support the hypothesis that RIF ATP contributes to TGF-mediated changes in RVR.

The findings that GFR and U_NaV were significantly increased by nifedipine infusion suggest that nifedipine infusion alone should have also increased basal RIF ATP levels. However, intra-arterial infusion of nifedipine did not significantly increase RIF ATP levels, indicating that the stimulus to the TGF mechanism by nifedipine was not sufficient to increase RIF ATP levels or that other counteracting mechanisms associated with decreases in RAP or increased RBF prevented the anticipated changes in RIF ATP. Micropuncture and clearance studies have shown that the primary tubular action sites of dihydropyridine calcium antagonists are at distal convoluted tubules and collecting ducts (7). It has also been suggested that the diuretic action of dihydropyridine calcium antagonists is partially dependent on the increases in medullary blood flow (1). Therefore, it is possible that although nifedipine increases GFR, the amount of nifedipine-induced increases in solute delivery at the macula densa cells may be lower compared with acetazolamide infusion, which inhibits proximal reabsorption rate. Another possibility is that our methods using microdialysis technique may fail to detect small increases in RIF ATP concentrations in response to nifedipine infusion. It is also possible that the increase in RBF caused by nifedipine led to increased washout of RIF ATP, which counteracted the effects of increased ATP release to increase RIF ATP levels. Nevertheless, the failure to demonstrate an increase in ATP levels directly in response to the administration of nifedipine introduces a note of caution in our interpretation.

Several micropuncture studies (8, 29) have demonstrated that local administration of high doses of adenosine receptor antagonists decreases the magnitude of TGF-mediated reductions in stop-flow pressure and single nephron filtration rate in response to increases in the distal nephron perfusion rate. Furthermore, normal TGF responses are not present in adenosine A₁ receptor-deficient mice (3, 30). These data suggest a role for adenosine in the transmission of the TGF signals. However, this hypothesis has remained controversial because adenosine antagonists do not block RBF and GFR autoregulation (10, 27) or TGF responses (8, 17). Furthermore, recent studies have shown that RIF adenosine levels were not altered in response to reductions in RAP within the autoregulatory range (21, 22). In addition, RIF adenosine levels were not altered significantly during augmented TGF activity by acetazolamide or inhibition of the TGF response by furosemide, indicating that there is no relationship between the change in the macula densa stimulus and RIF concentrations of adenosine (21, 22). It should also be noted that, although ATP can be metabolized to ADP, AMP, and adenosine (19), complete and immediate hydrolysis of all available ATP would still not yield sufficiently high levels of these substances to cause comparable vasoconstriction, as described previously (21–24).

In summary, the present study demonstrates that the changes in RIF ATP concentrations can occur in the absence of autoregulatory or TGF-related changes in RVR. The results are consistent with the hypothesis that autoregulatory and TGF-dependent adjustments in RVR are mediated by the corresponding changes in RIF ATP concentrations (2, 5, 11–13, 15–17, 19, 21–24, 35). It has been recognized that impairment of renal autoregulation and the TGF mechanism closely contribute to the development of hypertension and renal injury (19, 24, 34). In addition, potential pathological roles of renal interstitial ATP have also been suggested by several recent studies (4, 6, 24). It is possible that TGF- and autoregulatory-mediated increases in RIF ATP concentrations, if sustained for a prolonged period, could contribute to hypertension-related renal injury. Accordingly, future studies will be needed to determine the dynamics of RIF ATP and its roles in the development of hypertension and renal injury.

	GRANTS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION GRANTS REFERENCES

 
This work was supported by grants from the National Heart, Lung, and Blood Institute (HL-18426), Health Excellence Fund from the Louisiana Board of Regents, Center of Biomedical Research Excellence grant from the Institutional development Award Program of the National Center of Research Resources (P20RR017659), grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (15790136), and the Salt Sciences Research Grant (05C2).

	ACKNOWLEDGMENTS

 
We gratefully acknowledge the technical assistance of Eri Hiramoto (Okayama University Medical School, Okayama, Japan). We are also grateful to Drs. Hidehiko Sakurai, Kimihiro Mabuchi, and Noriaki Kato (Toyobo KK, Otsu, Japan) for supplying the dialysis membrane and steel tubes. We appreciate the assistance of Debbie Olavarrieta in preparation of the paper.

	FOOTNOTES

 

Address for reprint requests and other correspondence: A. Nishiyama, Dept. of Pharmacology, Kagawa Univ. Medical School, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan (e-mail: akira{at}kms.ac.jp)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

	REFERENCES

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION GRANTS REFERENCES

 

1. Abe Y, Komori T, Miura K, Takada T, Imanishi M, Okahara T, and Yamamoto K. Effects of the calcium antagonist nicardipine on renal function and renin release in dogs. J Cardiovasc Pharmacol 5: 254–259, 1983.[Web of Science][Medline]
2. Bell PD, Lapointe JY, Sabirov R, Hayashi S, Peti-Peterdi J, Manabe K, Kovacs G, and Okada Y. Macula densa cell signaling involves ATP release through a maxi anion channel. Proc Natl Acad Sci USA 100: 4322–4327, 2003.[Abstract/Free Full Text]
3. Brown R, Ollerstam A, Johansson B, Skott O, Gebre-Medhin S, Fredholm B, and Persson AE. Abolished tubuloglomerular feedback and increased plasma renin in adenosine A₁ receptor-deficient mice. Am J Physiol Regul Integr Comp Physiol 281: R1362–R1367, 2001.[Abstract/Free Full Text]
4. Burnstock G. Purinergic signaling and vascular cell proliferation and death. Arterioscler Thromb Vasc Biol 22: 364–373, 2002.[Abstract/Free Full Text]
5. Chan CM, Unwin RJ, Bardini M, Oglesby IB, Ford AP, Townsend-Nicholson A, and Burnstock G. Localization of P2X₁ purinoceptors by autoradiography and immunohistochemistry in rat kidneys. Am J Renal Physiol 274: F799–F804, 1998.[Abstract/Free Full Text]
6. Chan CM, Unwin RJ, and Burnstock G. Potential functional roles of extracellular ATP in kidney and urinary tract. Exp Nephrol 6: 200–207, 1998.[CrossRef][Web of Science][Medline]
7. Dibona GF and Sawin LL. Renal tubular site of action of felodipine. J Pharmacol Exp Ther 228: 420–424, 1984.[Abstract/Free Full Text]
8. Franco M, Bell PD, and Navar LG. Effect of adenosine A1 analogue on tubuloglomerular feedback mechanism. Am J Physiol Renal Fluid Electrolyte Physiol 257: F231–F236, 1989.[Abstract/Free Full Text]
9. Gourine AV, Hu Q, Sander PR, Kuzmin AI, Hanafy N, Davydova SA, Zaretsky DV, and Zhang J. Interstitial purine metabolites in hearts with LV remodeling. Am J Physiol Heart Circ Physiol 286: H677–H684, 2004.[Abstract/Free Full Text]
10. Ibarrola AM, Inscho EW, Vari RC, and Navar LG. Influence of adenosine receptor blockade on renal function and renal autoregulation. J Am Soc Nephrol 2: 991–999, 1991.[Abstract]
11. Inscho EW. P2 receptors in the regulation of renal microvascular function. Am J Physiol Renal Physiol 280: F927–F944, 2001.[Abstract/Free Full Text]
12. Inscho EW, Cook AK, Imig JD, Vial C, and Evans RJ. Physiological role for P2X1 receptors in renal microvascular autoregulatory behavior. J Clin Invest 112: 1895–1905, 2003.[CrossRef][Web of Science][Medline]
13. Inscho EW, Cook AK, and Navar LG. Pressure-mediated vasoconstriction of juxtamedullary afferent arterioles involves P2-purinoceptor activation. Am J Physiol Renal Fluid Electrolyte Physiol 271: F1077–F1085, 1996.[Abstract/Free Full Text]
14. Jin XH, McGrath HE, Gildea JJ, Siragy HM, Felder RA, and Carey RM. Renal interstitial guanosine cyclic 3',5'-monophosphate mediates pressure-natriuresis via protein kinase G. Hypertension 43: 1133–1139, 2004.[Abstract/Free Full Text]
15. Komlosi P, Peti-Peterdi J, Fuson AL, Fintha A, Rosivall L, and Bell PD. Macula densa basolateral ATP release is regulated by luminal [NaCl] and dietary salt intake. Am J Physiol Renal Physiol 286: F1054–F1058, 2004.[Abstract/Free Full Text]
16. Majid DSA, Inscho EW, and Navar LG. P2 purinoceptor saturation by adenosine triphosphate impairs renal autoregulation in dogs. J Am Soc Nephrol 10: 492–498, 1999.[Abstract/Free Full Text]
17. Mitchell KD and Navar LG. Modulation of tubuloglomerular feedback responsiveness by extracellular ATP. Am J Physiol Renal Fluid Electrolyte Physiol 264: F458–F466, 1993.[Abstract/Free Full Text]
18. Navar LG, Champion WJ, and Thomas CE. Effects of calcium channel blockade on renal vascular resistance responses to changes in perfusion pressure and angiotensin-converting enzyme inhibition in dogs. Circ Res 58: 874–881, 1986.[Abstract/Free Full Text]
19. Navar LG, Inscho EW, Majid DSA, Imig JD, Harrison-Bernard LM, and Mitchell KD. Paracrine regulation of the renal microcirculation. Physiol Rev 76: 425–536, 1996.[Abstract/Free Full Text]
20. Ninomiya H, Otani H, Lu K, Uchiyama T, Kido M, and Imamura H. Complementary role of extracellular ATP and adenosine in ischemic preconditioning in the rat heart. Am J Physiol Heart Circ Physiol 282: H1810–H1820, 2002.[Abstract/Free Full Text]
21. Nishiyama A, Majid DSA, Taher KA, Miyatake A, and Navar LG. Relation between renal interstitial ATP concentrations and autoregulation-mediated changes in renal vascular resistance. Circ Res 86: 656–662, 2000.[Abstract/Free Full Text]
22. Nishiyama A, Majid DSA, Walker M, III, Miyatake A, and Navar LG. Renal interstitial ATP responses to changes in arterial pressure during alterations in tubuloglomerular feedback activity. Hypertension 37: 753–759, 2001.[Abstract/Free Full Text]
23. Nishiyama A and Navar LG. ATP mediates tubuloglomerular feedback. Am J Physiol Regul Integr Comp Physiol 283: R273–R275, 2002.[Free Full Text]
24. Nishiyama A, Rahman M, and Inscho EW. Role of interstitial ATP and adenosine in the regulation of renal hemodynamics and microvascular function. Hypertens Res 27: 791–804, 2004.[CrossRef][Web of Science][Medline]
25. Novak I. ATP as a signaling molecule: the exocrine focus. News Physiol Sci 18: 12–17, 2003.[Abstract/Free Full Text]
26. Persson AE and Wright FS. Evidence for feedback mediated reduction of glomerular filtration rate during infusion of acetazolamide. Acta Physiol Scand 114: 1–7, 1982.[Web of Science][Medline]
27. Premen AJ, Hall JE, Mizelle HL, and Cornell JE. Maintenance of renal autoregulation during infusion of aminophylline or adenosine. Am J Physiol Renal Fluid Electrolyte Physiol 248: F366–F373, 1985.[Abstract/Free Full Text]
28. Schnermann J and Marver D. ATPase activity in macula densa cells of the rabbit kidney. Pflügers Arch 407: 82–86, 1986.[CrossRef][Web of Science][Medline]
29. Schnermann J, Weihprecht H, and Briggs JP. Inhibition of tubuloglomerular feedback during adenosine1 receptor blockade. Am J Physiol Renal Fluid Electrolyte Physiol 258: F553–F561, 1990.[Abstract/Free Full Text]
30. Sun D, Samuelson LC, Yang T, Huang Y, Paliege A, Saunders T, Briggs J, and Schnermann J. Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors. Proc Natl Acad Sci USA 98: 9983–9988, 2001.[Abstract/Free Full Text]
31. Takenaka T, Harrison-Bernard LM, Inscho EW, Carmines PK, and Navar LG. Autoregulation of afferent arteriolar blood flow in juxtamedullary nephrons. Am J Physiol Renal Fluid Electrolyte Physiol 267: F879–F887, 1994.[Abstract/Free Full Text]
32. Walker M, III, Harrison-Bernard LM, Cook AK, and Navar LG. Dynamic interaction between myogenic and TGF mechanisms in afferent arteriolar blood flow autoregulation. Am J Physiol Renal Physiol 279: F858–F865, 2000.[Abstract/Free Full Text]
33. White SM, Imig JD, and Inscho EW. Calcium signaling pathways utilized by P2X receptors in preglomerular vascular smooth muscle cells. Am J Physiol Renal Physiol 280: F1054–F1061, 2001.[Abstract/Free Full Text]
34. Wilcox CS. Redox regulation of the afferent arteriole and tubuloglomerular feedback. Acta Physiol Scand 179: 217–223, 2003.[CrossRef][Web of Science][Medline]
35. Zhao X, Inscho EW, Bondlela M, Falck JR, and Imig JD. The CYP450 hydroxylase pathway contributes to P2X receptor-mediated afferent arteriolar vasoconstriction. Am J Physiol Heart Circ Physiol 281: H2089–H2096, 2001.[Abstract/Free Full Text]

This article has been cited by other articles:

				A. Just and W. J. Arendshorst A novel mechanism of renal blood flow autoregulation and the autoregulatory role of A1 adenosine receptors in mice Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1489 - F1500. [Abstract] [Full Text] [PDF]

				Z. Guan, D. A. Osmond, and E. W. Inscho Purinoceptors in the Kidney Experimental Biology and Medicine, June 1, 2007; 232(6): 715 - 726. [Abstract] [Full Text] [PDF]

				W. A. Cupples and B. Braam Assessment of renal autoregulation Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1105 - F1123. [Abstract] [Full Text] [PDF]

				J. Peti-Peterdi Calcium wave of tubuloglomerular feedback Am J Physiol Renal Physiol, August 1, 2006; 291(2): F473 - F480. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 290/2/H772    most recent 00242.2005v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Nishiyama, A. Articles by Navar, L. G. Search for Related Content PubMed PubMed Citation Articles by Nishiyama, A. Articles by Navar, L. G.