Eicosanoid regulation of the renal vasculature

2000 ◽  
Vol 279 (6) ◽  
pp. F965-F981 ◽  
Author(s):  
John D. Imig
Keyword(s):  
Blood Flow ◽  
Arachidonic Acid ◽  
Renal Blood Flow ◽  
Stress Responses ◽  
Tubuloglomerular Feedback ◽  
Renal Vasculature ◽  
Renal Hemodynamic ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites ◽  
Cox 2

Even though it has been recognized that arachidonic acid metabolites, eicosanoids, play an important role in the control of renal blood flow and glomerular filtration, several key observations have been made in the past decade. One major finding was that two distinct cyclooxygenase (COX-1 and COX-2) enzymes exist in the kidney. A renewed interest in the contribution of cyclooxygenase metabolites in tubuloglomerular feedback responses has been sparked by the observation that COX-2 is constitutively expressed in the macula densa area. Arachidonic acid metabolites of the lipoxygenase pathway appear to be significant factors in renal hemodynamic changes that occur during disease states. In particular, 12( S)- hydroxyeicosatetraenoic acid may be important for the full expression of the renal hemodynamic actions in response to angiotensin II. Cytochrome P-450 metabolites have been demonstrated to possess vasoactive properties, act as paracrine modulators, and be a critical component in renal blood flow autoregulatory responses. Last, peroxidation of arachidonic acid metabolites to isoprostanes appears to be involved in renal oxidative stress responses. The recent developments of specific enzymatic inhibitors, stable analogs, and gene-disrupted mice and in antisense technology are enabling investigators to understand the complex interplay by which eicosanoids control renal blood flow.

The step response: a method to characterize mechanisms of renal blood flow autoregulation

2003 ◽  
Vol 285 (4) ◽  
pp. F758-F764 ◽  
Author(s):  
T. Wronski ◽  
E. Seeliger ◽  
P. B. Persson ◽  
C. Forner ◽  
C. Fichtner ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Renal Perfusion ◽  
Oscillation Period ◽  
Tubuloglomerular Feedback ◽  
Step Response ◽  
Myogenic Response ◽  
Renal Vasculature ◽  
The Individual ◽  
Reported Data

Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow (RBF) is mediated by the rapid myogenic response, by the slower tubuloglomerular feedback (TGF) mechanism, and, possibly, by an even slower third mechanism. To evaluate the individual contribution of these mechanisms to RBF autoregulation, we analyzed the response of RBF to a step increase in RPP. In anesthetized rats, the suprarenal aorta was occluded for 30 s, and then the occlusion was released to induce a step increase in RPP. Three dampened oscillations were observed; their oscillation periods ranged from 9.5 to 13 s, from 34.2 to 38.6 s, and from 100.5 to 132.2 s, respectively. The two faster oscillations correspond with previously reported data on the myogenic mechanism and the TGF. In accordance, after furosemide, the amplitude of the intermediate oscillation was significantly reduced. Inhibition of nitric oxide synthesis by Nω-nitro-l-arginine methyl ester significantly increased the amplitude of the 10-s oscillation. It is concluded that the parameters of the dampened oscillations induced by the step increase in RPP reflect properties of autoregulatory mechanisms. The oscillation period characterizes the individual mechanism, the dampening is a measure for the stability of the regulation, and the square of the amplitudes characterizes the power of the respective mechanism. In addition to the myogenic response and the TGF, a third rather slow mechanism of RBF autoregulation exists.

Eicosanoids and renal vascular function in diseases

2006 ◽  
Vol 111 (1) ◽  
pp. 21-34 ◽  
Author(s):  
John D. Imig
Keyword(s):  
Metabolic Syndrome ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Arachidonic Acid ◽  
Renal Disease ◽  
Vascular Function ◽  
Renal Vasculature ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites ◽  
Renal Vascular

Arachidonic acid metabolites are vital for the proper control of renal haemodynamics and, when not properly controlled, can contribute to renal vascular injury and end-stage renal disease. Three major enzymatic pathways, COX (cyclo-oxygenase), CYP450 (cytochrome P450) and LOX (lipoxygenase), are responsible for the metabolism of arachidonic acid metabolites to bioactive eicosanoids. These eicosanoids can dilate or constrict the renal vasculature and maintain vascular resistance in the face of changing vasoactive hormones. Renal vascular generation of eicosanoids is altered in pathophysiological conditions such as hypertension, diabetes, metabolic syndrome and acute renal failure. Experimental evidence supports the concept that altered eicosanoid metabolism contributes to renal haemodynamic alterations and the development and progression of nephropathy. The possible beneficial renal vascular actions of enzymatic inhibitors, eicosanoid analogues and receptor antagonists have been examined in hypertension, diabetes and metabolic syndrome. This review highlights the roles of renal vascular eicosanoids in the pathogenesis of nephropathy and therapeutic targets for renal disease related to hypertension, diabetes, metabolic syndrome and acute renal failure.

scholarly journals Time-Dependent Autoregulation of Renal Blood Flow in Conscious Rats

2001 ◽  
Vol 12 (11) ◽  
pp. 2253-2262
Author(s):  
BERT FLEMMING ◽  
NICOLE ARENZ ◽  
ERDMANN SEELIGER ◽  
THOMAS WRONSKI ◽  
KATHARINA STEER ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Dynamic Properties ◽  
Rate Of Change ◽  
Tubuloglomerular Feedback ◽  
Operating Pressure ◽  
Renal Vasculature ◽  
Pressure Flow ◽  
Conscious Rats ◽  
Maximum Conductance

Abstract. Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow is mediated by a rapid myogenic response and a slower tubuloglomerular feedback mechanism. In 25 male conscious rats, ramp-shaped changes in RPP were induced to quantify dynamic properties of autoregulation. Decremental RPP ramps immediately followed by incremental ramps were made for four different rates of change, ranging from 0.118 to 1.056 mmHg/s. Renal blood flow and cortical and medullary fluxes were assessed, and the corresponding relative conductance values were calculated continuously. During RPP decrements, conductance increased. With increasing rate of change of RPP decrements, maximum conductance increased from 10% to 80%, as compared with control. This response, which indicates the magnitude of autoregulation, was more pronounced in cortical versus medullary vasculature. Pressure at maximum conductance decreased with increasing rate of change of RPP decrements from 88 to 72 mmHg. During RPP increments, dependence of maximum conductance changes on the rate of change was enhanced (-20 to 110% of control). Thus, a hysteresis-like asymmetry between RPP decrements and increments, a resetting of autoregulation, was observed, which in direction and magnitude depended on the rate of change and duration of RPP changes. In conclusion, renal vascular responses to changes in RPP are highly dependent on the dynamics of the error signal. Furthermore, the method presented allows differentiated stimulation of various static and dynamic components of pressure-flow relationship and, thus, a direct assessment of the magnitudes and operating pressure range of active mechanisms of pressure-flow relationships.

scholarly journals EFFECTS OF ARACHIDONIC ACID METABOLITES ON NASAL MUCOSAL BLOOD FLOW

1999 ◽  
Vol 38 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Mayumi Komori ◽  
Masato Miwa ◽  
Mitsuyoshi Hirano ◽  
Toshiko Mamiya ◽  
Yuka Kondo ◽  
...  
Keyword(s):  
Blood Flow ◽  
Arachidonic Acid ◽  
Mucosal Blood Flow ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites

scholarly journals Continuously measured renal blood flow does not increase in diabetes if nitric oxide synthesis is blocked

2008 ◽  
Vol 295 (5) ◽  
pp. F1449-F1456 ◽  
Author(s):  
Tracy D. Bell ◽  
Gerald F. DiBona ◽  
Rachel Biemiller ◽  
Michael W. Brands
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Function Analysis ◽  
Control Period ◽  
Power Spectra ◽  
Tubuloglomerular Feedback ◽  
Left Renal Artery ◽  
Renal Vasculature ◽  
Transfer Function Analysis

This study used 16 h/day measurement of renal blood flow (RBF) and arterial pressure (AP) to determine the role of nitric oxide (NO) in mediating the renal vasodilation caused by onset of type 1 diabetes. The AP and RBF power spectra were used to determine the autoregulatory efficiency of the renal vasculature. Rats were instrumented with artery and vein catheters and a Transonic flow probe on the left renal artery and were divided randomly into four groups: control (C), diabetes (D), control plus nitro-l-arginine methyl ester (l-NAME; CL), and diabetes plus l-NAME (DL). Mean AP averaged 90 ± 1 and 121 ± 1 mmHg in the D and DL groups, respectively, during the control period, and RBF averaged 5.9 ± 1.2 and 5.7 ± 0.7 ml/min, respectively. Respective C and CL groups were not different. Onset of diabetes (streptozotocin 40 mg/kg iv) in D rats increased RBF gradually, but it averaged 55% above control by day 14. In DL rats, on the other hand, RBF remained essentially constant, tracking with RBF in the nondiabetic C and CL groups for the 2-wk period. Diabetes did not change mean AP in any group. Transfer function analysis revealed impaired dynamic autoregulation of RBF overall, including the frequency range of tubuloglomerular feedback (TGF), and l-NAME completely prevented those changes as well. These data strongly support a role for NO in causing renal vasodilation in diabetes and suggest that an effect of NO to blunt RBF autoregulation may play an important role.

A Role for Tubuloglomerular Feedback in Chronic Partial Ureteral Obstruction

Physiology ◽  
1993 ◽  
Vol 8 (2) ◽  
pp. 74-79
Author(s):  
P Morsing
Keyword(s):  
Renal Function ◽  
Arachidonic Acid ◽  
Ureteral Obstruction ◽  
Volume Expansion ◽  
Filtration Rate ◽  
Extracellular Volume ◽  
Tubuloglomerular Feedback ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites ◽  
Extracellular Volume Expansion

Animals with partial ureteral obstruction have an inability to increase urinary output and glomerular filtration rate in response to an extracellular volume expansion. The mechanism may be a paradoxical resetting of tubuloglomerular feedback in the obstructed kidney, which impacts the roles of arachidonic acid metabolites and kinins in renal function.

Attenuation of postischemic brain hypoperfusion and reperfusion injury by the cyclooxygenase—lipoxygenase inhibitor BW755C

1995 ◽  
Vol 83 (1) ◽  
pp. 99-104 ◽  
Author(s):  
Jun Chen ◽  
Philip R. Weinstein ◽  
Steven H. Graham
Keyword(s):  
Blood Flow ◽  
Arachidonic Acid ◽  
Reperfusion Injury ◽  
Evans Blue ◽  
Infarct Volume ◽  
Blue Dye ◽  
Lipoxygenase Inhibitor ◽  
Brain Barrier Permeability ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites

✓ Arachidonic acid metabolites are believed to be important mediators of tissue injury during reperfusion after cerebral ischemia. To determine whether inhibiting the oxygen-dependent metabolism of arachidonic acid would reduce reperfusion injury, we administered the mixed cyclooxygenase—lipoxygenase inhibitor BW755C (3-amino-1-[m(trifluoromethyl) phenyl]-2-pyrazoline) near the time of reperfusion in a rat model of temporary focal ischemia. The duration of ischemia + reperfusion was 2 hours + 22 hours, 3 hours + 3 hours, or 3 hours + 21 hours. The effects of drug or saline treatment on infarct volume, blood-brain barrier permeability, and blood flow were determined. Cortical blood flow was monitored with laser Doppler flowmetry and blood-brain barrier permeability was evaluated by the Evans blue dye method. Infarct volume was determined in all groups by computerized image analysis of Nissl-stained sections. We found that BW755C treatment significantly attenuated delayed postischemic hypoperfusion in the 3 + 3 group (p < 0.05) and reduced the volume of Evans blue dye staining in the cortex (p < 0.01) and basal ganglia (p < 0.05). Hemispheric swelling was reduced in all treatment groups (p < 0.01), as was total infarct volume in the ischemic hemisphere (p < 0.05). These results support the hypothesis that arachidonic acid metabolites contribute to acute postischemic reperfusion injury and suggest that using a mixed cyclooxygenase—lipoxygenase inhibitor as an adjunct to thrombolytic or revascularization therapy could lengthen the ischemia time after which reperfusion is beneficial.

Sympathetic modulation of renal blood flow by rilmenidine and captopril: central vs. peripheral effects

2002 ◽  
Vol 282 (1) ◽  
pp. F113-F123 ◽  
Author(s):  
Ben J. A. Janssen ◽  
Elena V. Lukoshkova ◽  
Geoffrey A. Head
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Hemodynamic Response ◽  
Simultaneous Recording ◽  
Tubuloglomerular Feedback ◽  
Renal Nerves ◽  
Vasodilator Effect ◽  
Renal Hemodynamic ◽  
Sympathetic Modulation ◽  
Conscious Rabbits

Renal blood flow (RBF) is modulated by renal sympathetic nerve activity (RSNA). However, agents that are supposed to reduce sympathetic tone, such as rilmenidine and captopril, influence RBF also by direct arteriolar effects. The present study was designed to test to what extent the renal nerves contribute to the renal hemodynamic response to rilmenidine and captopril. We used a technique that allows simultaneous recording of RBF and RSNA to the same kidney in conscious rabbits. We compared the dose-dependent effects of rilmenidine (0.01–1 mg/kg) and captopril (0.03–3 mg/kg) on RBF and RSNA in intact and renal denervated (RNX) rabbits. Because rilmenidine and captopril lower blood pressure, studies were also performed in sinoaortically denervated (SAD) rabbits to determine the role of the baroreflex in the renal hemodynamic response. Rilmenidine reduced arterial pressure, RBF, and RSNA dose dependently. In intact rabbits ( n = 10), renal conductance (RC) remained unaltered (3 ± 5%), even after the 1-mg/kg dose, which completely abolished RSNA. In RNX rabbits ( n = 6), RC fell by 18 ± 5%, whereas in SAD rabbits ( n = 7) RC increased by 30 ± 20% after rilmenidine. In intact rabbits, captopril increased RSNA maximally by 64 ± 8%. RSNA did not rise in SAD rabbits. Despite the differential response or absence of RSNA, captopril increased RC to a comparable degree (maximally 40–50%) in all three groups. Using spectral analysis techniques, we found that in all groups, independently of ongoing RSNA, captopril, but not rilmenidine, attenuated both myogenic (0.07–0.25 Hz) and tubuloglomerular feedback (0.01–0.07 Hz) related fluctuations in RC. We conclude that, in conscious rabbits, the renal vasodilator effect of rilmenidine depends on the level of ongoing RSNA. Its sympatholytic effect is, however, blunted by a direct arteriolar vasoconstrictor effect. In contrast, the renal vasodilator effect of captopril is not modulated by ongoing RSNA and is associated with impairment of autoregulation of RBF.

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