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Physiol. Rev. 76: 425-536, 1996;
0031-9333/96 $15.00
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Physiological Reviews, Vol 76, 425-536, Copyright © 1996 by American Physiological Society

JOURNAL ARTICLE

Paracrine regulation of the renal microcirculation

L. G. Navar, E. W. Inscho, S. A. Majid, J. D. Imig, L. M. Harrison-Bernard and K. D. Mitchell
Department of Physiology, Tulane University Medical Center, New Orleans, Louisiana, USA.

There has been an explosive growth of interest in the multiple interacting paracrine systems that influence renal microvascular function. This review first discusses the membrane activation mechanisms for renal vascular control. Evidence is provided that there are differential activating mechanisms regulating pre- and postglomerular arteriolar vascular smooth muscle cells. The next section deals with the critical role of the endothelium in the control of renal vascular function and covers the recent findings related to the role of nitric oxide and other endothelial-derived factors. This section is followed by an analysis of the roles of vasoactive paracrine systems that have their origin from adjoining tubular structures. The interplay of signals between the epithelial cells and the vascular network to provide feedback regulation of renal hemodynamics is developed. Because of their well-recognized contributions to the regulation of renal microvascular function, three major paracrine systems are discussed in separate sections. Recent findings related to the role of intrarenally formed angiotensin II and the prominence of the AT1 receptors are described. The possible contribution of purinergic compounds is then discussed. Recognition of the emerging role of extracellular ATP operating via P2 receptors as well as the more recognized functions of the P1 receptors provides fertile ground for further studies. In the next section, the family of vasoactive arachidonic acid metabolites is described. Possibilities for a myriad of interacting functions operating both directly on vascular smooth muscle cells and indirectly via influences on endothelial and epithelial cells are discussed. Particular attention is given to the more recent developments related to hemodynamic actions of the cytochrome P-450 metabolites. The final section discusses unique mechanisms that may be responsible for differential regulation of medullary blood flow by locally formed paracrine agents. Several sections provide perspectives on the complex interactions among the multiple mechanisms responsible for paracrine regulation of the renal microcirculation. This plurality of regulatory interactions highlights the need for experimental strategies that include integrative approaches that allow manifestation of indirect as well as direct influences of these paracrine systems on renal microvascular function.


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Effects of ACE inhibition and AT1-receptor blockade on haemodynamic responses to L-arginine in Type 1 diabetes
Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 33 - 38.
[Abstract] [PDF]

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 HypertensionHome page
R. Liu and A. E. G. Persson
Angiotensin II Stimulates Calcium and Nitric Oxide Release From Macula Densa Cells Through AT1 Receptors
Hypertension, March 1, 2004; 43(3): 649 - 653.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
M.-G. Feng, M. Li, and L. G. Navar
T-type calcium channels in the regulation of afferent and efferent arterioles in rats
Am J Physiol Renal Physiol, February 1, 2004; 286(2): F331 - F337.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
S. Arima, K. Kohagura, H.-L. Xu, A. Sugawara, A. Uruno, F. Satoh, K. Takeuchi, and S. Ito
Endothelium-Derived Nitric Oxide Modulates Vascular Action of Aldosterone in Renal Arteriole
Hypertension, February 1, 2004; 43(2): 352 - 357.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
M. Z. Haque and D. S. A. Majid
Assessment of Renal Functional Phenotype in Mice Lacking gp91PHOX Subunit of NAD(P)H Oxidase
Hypertension, February 1, 2004; 43(2): 335 - 340.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
G. O. Ogungbade, L. A. Akinsanmi, H. Jiang, and A. O. Oyekan
Role of epoxyeicosatrienoic acids in renal functional response to inhibition of NO production in the rat
Am J Physiol Renal Physiol, November 1, 2003; 285(5): F955 - F964.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
G. Perez de Lema, C. de Wit, C. D. Cohen, E. Nieto, A. Molina, B. Banas, B. Luckow, A. B. Vicente, F. Mampaso, and D. Schlondorff
Angiotensin Inhibition Reduces Glomerular Damage and Renal Chemokine Expression in MRL/lpr Mice
J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 275 - 281.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
M. Baum, S. Loleh, N. Saini, M. Seikaly, V. Dwarakanath, and R. Quigley
Correction of proximal tubule phosphate transport defect in Hyp mice in vivo and in vitro with indomethacin
PNAS, September 16, 2003; 100(19): 11098 - 11103.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
A. Cavarape, J. Bauer, E. Bartoli, K. Endlich, and N. Parekh
Effects of angiotensin II, arginine vasopressin and tromboxane A2 in renal vascular bed: role of rho-kinase
Nephrol. Dial. Transplant., September 1, 2003; 18(9): 1764 - 1769.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Just and W. J. Arendshorst
Dynamics and contribution of mechanisms mediating renal blood flow autoregulation
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R619 - R631.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
M.-S. Wu, C.-W. Yang, C.-T. Chang, M. Bens, and A. Vandewalle
Cyclosporin increases the density of angiotensin II subtype 1 (AT1) receptors in mouse medullary thick ascending limb cells
Nephrol. Dial. Transplant., August 1, 2003; 18(8): 1458 - 1465.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
M.-S. Wu, C.-W. Yang, C.-T. Chang, M. Bens, and A. Vandewalle
Cyclosporin increases the density of angiotensin II subtype 1 (AT1) receptors in mouse medullary thick ascending limb cells
Nephrol. Dial. Transplant., August 1, 2003; 18(88): 1458 - 1465.
[Abstract] [Full Text]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. M. Sorensen, P. P. Leyssac, O. Skott, and N.-H. Holstein-Rathlou
NO mediates downregulation of RBF after a prolonged reduction of renal perfusion pressure in SHR
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R329 - R338.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. W. Inscho
Modulation of renal microvascular function by adenosine
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R23 - R25.
[Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
T. Takenaka, Y. Ohno, K. Hayashi, T. Saruta, and H. Suzuki
Governance of arteriolar oscillation by ryanodine receptors
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R125 - R131.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
A. K. Bidani, R. Hacioglu, I. Abu-Amarah, G. A. Williamson, R. Loutzenhiser, and K. A. Griffin
"Step" vs. "dynamic" autoregulation: implications for susceptibility to hypertensive injury
Am J Physiol Renal Physiol, July 1, 2003; 285(1): F113 - F120.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. W. Cowley Jr., T. Mori, D. Mattson, and A.-P. Zou
Role of renal NO production in the regulation of medullary blood flow
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1355 - R1369.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Marchetti, C. M. B. Helou, C. Chollet, R. Rajerison, and F. Alhenc-Gelas
Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems: ACE and non-ACE mediated effect of angiotensin I on intracellular calcium mobilization in rat glomerular arterioles
Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1933 - H1941.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
B. Badzynska, M. Grzelec-Mojzesowicz, and J. Sadowski
Prostaglandins but not nitric oxide protect renal medullary perfusion in anaesthetised rats receiving angiotensin II
J. Physiol., May 1, 2003; 548(3): 875 - 880.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
P. D. Bell, J.-Y. Lapointe, R. Sabirov, S. Hayashi, J. Peti-Peterdi, K.-i. Manabe, G. Kovacs, and Y. Okada
Macula densa cell signaling involves ATP release through a maxi anion channel
PNAS, April 1, 2003; 100(7): 4322 - 4327.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
G. Li Volti, F. Seta, M. L. Schwartzman, A. Nasjletti, and N. G. Abraham
Heme Oxygenase Attenuates Angiotensin II-Mediated Increase in Cyclooxygenase-2 Activity in Human Femoral Endothelial Cells
Hypertension, March 1, 2003; 41(3): 715 - 719.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
T. L. Pallone, Z. Zhang, and K. Rhinehart
Physiology of the renal medullary microcirculation
Am J Physiol Renal Physiol, February 1, 2003; 284(2): F253 - F266.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. Lopez, M. T. Llinas, F. Roig, and F. J. Salazar
Role of nitric oxide and cyclooxygenase-2 in regulating the renal hemodynamic response to norepinephrine
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R488 - R493.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
A. Cavarape, N. Endlich, R. Assaloni, E. Bartoli, M. Steinhausen, N. Parekh, and K. Endlich
Rho-Kinase Inhibition Blunts Renal Vasoconstriction Induced by Distinct Signaling Pathways In Vivo
J. Am. Soc. Nephrol., January 1, 2003; 14(1): 37 - 45.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
D. L. Mattson
Importance of the renal medullary circulation in the control of sodium excretion and blood pressure
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2003; 284(1): R13 - R27.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
S. Gschwend, H. Buikema, G. Navis, R. H. Henning, D. de Zeeuw, and R. P. E. van Dokkum
Endothelial Dilatory Function Predicts Individual Susceptibility to Renal Damage in the 5/6 Nephrectomized Rat
J. Am. Soc. Nephrol., December 1, 2002; 13(12): 2909 - 2915.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
A. Ichihara, M. Hayashi, Y. Koura, Y. Tada, T. Sugaya, N. Hirota, and T. Saruta
Blunted Tubuloglomerular Feedback by Absence of Angiotensin Type 1A Receptor Involves Neuronal NOS
Hypertension, December 1, 2002; 40(6): 934 - 939.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
A. Ollerstam and A.E. G Persson
Macula densa neuronal nitric oxide synthase
Cardiovasc Res, November 1, 2002; 56(2): 189 - 196.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
F. Roig, M. T. Llinas, R. Lopez, and F. J. Salazar
Role of Cyclooxygenase-2 in the Prolonged Regulation of Renal Function
Hypertension, November 1, 2002; 40(5): 721 - 728.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
Y. Aki, A. Nishiyama, A. Miyatake, S. Kimura, M. Kohno, and Y. Abe
Role of Adenosine A1 Receptor in Angiotensin II- and Norepinephrine-Induced Renal Vasoconstriction
J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 117 - 123.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
R. A. North
Molecular Physiology of P2X Receptors
Physiol Rev, October 1, 2002; 82(4): 1013 - 1067.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
A. Nishiyama, D. M. Seth, and L. G. Navar
Renal Interstitial Fluid Angiotensin I and Angiotensin II Concentrations during Local Angiotensin-Converting Enzyme Inhibition
J. Am. Soc. Nephrol., September 1, 2002; 13(9): 2207 - 2212.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
J. D. Imig, M. D. Breyer, and R. M. Breyer
Contribution of prostaglandin EP2 receptors to renal microvascular reactivity in mice
Am J Physiol Renal Physiol, September 1, 2002; 283(3): F415 - F422.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
S. Vanni, G. Polidori, I. Cecioni, S. Serni, M. Carini, and P. A. Modesti
ETB Receptor in Renal Medulla Is Enhanced by Local Sodium During Low Salt Intake
Hypertension, August 1, 2002; 40(2): 179 - 185.
[Abstract] [Full Text] [PDF]


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