Physiological and pathophysiological roles of oxygen radicals in the renal microvasculature

2002 ◽  
Vol 282 (2) ◽  
pp. R335-R342 ◽  
Author(s):  
Christine G. Schnackenberg
Keyword(s):  
Diabetes Mellitus ◽  
Oxygen Radicals ◽  
Vascular Tone ◽  
Tubuloglomerular Feedback ◽  
Normal Kidney ◽  
Renal Vasoconstriction ◽  
Increased Sensitivity ◽  
Renal Microvasculature ◽  
Renal Vascular ◽  
Renal Vascular Tone

The renal microvasculature is an important component in the regulation of kidney function. Recent studies suggest that oxygen radicals can contribute to the modulation of renal cortical and medullary microvascular function under normal conditions as well as in pathophysiological conditions such as diabetes mellitus and hypertension. This review focuses on studies that indicate oxygen radicals can cause renal vasoconstriction, mediate the vasoconstriction of other agonists, and modulate nitric oxide-dependent actions in the normal kidney. Hypertension and diabetes mellitus are associated with oxidative stress. Recent investigations suggest that oxygen radicals may contribute to the enhanced renal vascular tone, increased sensitivity to vasoconstrictors, impaired endothelium-dependent vasodilation, and enhanced tubuloglomerular feedback found in these pathophysiological conditions.

Stimulation of renin release by prostaglandin E2 is mediated by EP2 and EP4 receptors in mouse kidneys

2004 ◽  
Vol 287 (3) ◽  
pp. F427-F433 ◽  
Author(s):  
Frank Schweda ◽  
Jürgen Klar ◽  
Shuh Narumiya ◽  
Rolf M. Nüsing ◽  
Armin Kurtz
Keyword(s):  
Vascular Tone ◽  
Threshold Concentration ◽  
Renin Release ◽  
Receptor Subtypes ◽  
Wild Type ◽  
Adrenoceptor Agonist ◽  
Functional Relevance ◽  
Renal Vascular ◽  
Renal Vascular Tone ◽  
Stimulation Of

PGE2 is a potent stimulator of renin release. So far, the contribution of each of the four PGE2 receptor subtypes (EP1–EP4) in the regulation of renin release has not been characterized. Therefore, we investigated the effects PGE2 on renin secretion rates (RSR) from isolated, perfused kidneys of EP1−/−, EP2−/−, EP3−/−, EP4−/−, and wild-type mice. PGE2 concentration dependently stimulated RSR from kidneys of all four knockout strains with a threshold concentration of 1 nM in EP1−/−, EP2−/−, EP3−/−, and wild-type mice, whereas the threshold concentration was shifted to 10 nM in EP4−/− mice. Moreover, the maximum stimulation of RSR by PGE2 at 1 μM was significantly reduced in EP4−/− (12.8-fold of control) and EP2−/− (15.9-fold) compared with wild-type (20.7-fold), EP1−/− (23.8-fold), and EP3−/− (20.1-fold). In contrast, stimulation of RSR by either the loop diuretic bumetanide or the β-adrenoceptor agonist isoproterenol was similar in all strains. PGE2 exerted a dual effect on renal vascular tone, inducing vasodilatation at low concentrations (1 nmol/) and vasoconstriction at higher concentrations (100 nmol/) in kidneys of wild-type mice. In kidneys of EP2−/− as well as EP4−/− mice, vasodilatation at low PGE2 concentrations was prevented, whereas vasoconstriction at higher concentrations was augmented. In contrast, the vasodilatatory component was pronounced in kidneys of EP1 and EP3 knockout mice, whereas in both genotypes the vasoconstriction at higher PGE2 concentrations was markedly blunted. Our data provide evidence that PGE2 stimulates renin release via activation of EP2 and EP4 receptors, whereas EP1 and EP3 receptors appear to be without functional relevance in juxtaglomerular cells. In contrast, all four receptor subtypes are involved in the control of renal vascular tone, EP1 and EP3 receptors increasing, and EP2 as well as EP4 receptors, decreasing it.

Effect of Captopril on Renal Vascular Tone in Patients with Essential Hypertension

1979 ◽  
Vol 57 (s5) ◽  
pp. 421s-423s ◽  
Author(s):  
A. Mimran ◽  
H. R. Brunner ◽  
G. A. Turini ◽  
B. Waeber ◽  
D. Brunner
Keyword(s):  
Essential Hypertension ◽  
Vascular Tone ◽  
Sodium Intake ◽  
Renal Plasma Flow ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Urinary Potassium ◽  
Renal Vascular ◽  
Renal Vascular Tone

1. The effect of acute inhibition of angiotensin-converting enzyme by captopril (50 mg) on renal haemodynamics and function was assessed in nine patients with essential hypertension on unrestricted sodium intake (n = 8) or low sodium diet (n = 1). 2. Captopril induced a rapid and significant decrease in arterial pressure, which was maximal within 60 min. 3. Effective renal plasma flow (ERPF) increased, glomerular filtration rate (GFR) did not change and filtration fraction (FF) decreased after captopril. No change in sodium excretion and a decrease in urinary potassium occurred. 4. In the patient on low sodium diet, captopril induced striking increases in GFR and ERPF (64 and 106% respectively). 5. The logarithm of baseline plasma renin activity was positively correlated with the change in ERPF and negatively correlated with changes in FF and renal resistance. 6. The results indicate that in patients with essential hypertension angiotensin participates actvely in the maintenance of renal vascular tone at the efferent arteriolar level. A possible influence of kinins remains to be defined.

Interactions Between Neural and Hormonal Mediators of Renal Vascular Tone in Anaesthetized Rabbits

2003 ◽  
Vol 88 (2) ◽  
pp. 229-241 ◽  
Author(s):  
Sarah-Jane Guild ◽  
Carolyn J. Barrett ◽  
Roger G. Evans ◽  
Simon C. Malpas
Keyword(s):  
Vascular Tone ◽  
Renal Vascular ◽  
Renal Vascular Tone

Contribution of endothelin to renal vascular tone and autoregulation in the conscious dog

1999 ◽  
Vol 276 (3) ◽  
pp. F417-F424 ◽  
Author(s):  
Heike Berthold ◽  
Klaus Münter ◽  
Armin Just ◽  
Hartmut R. Kirchheim ◽  
Heimo Ehmke
Keyword(s):  
Time Course ◽  
Vascular Tone ◽  
Ace Inhibition ◽  
Renal Hemodynamics ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Renal Autoregulation ◽  
Arterial Blood ◽  
Renal Vascular ◽  
Renal Vascular Tone

Exogenous endothelin-1 (ET-1) is a strong vasoconstrictor in the canine kidney and causes a decrease in renal blood flow (RBF) by stimulating the ETA receptor subtype. The aim of the present study was to investigate the role of endogenously generated ET-1 in renal hemodynamics under physiological conditions. In six conscious foxhounds, the time course of the effects of the selective ETA receptor antagonist LU-135252 (10 mg/kg iv) on mean arterial blood pressure (MAP), heart rate (HR), RBF, and glomerular filtration rate (GFR), as well as its effects on renal autoregulation, were examined. LU-135252 increased RBF by 20% (from 270 ± 21 to 323 ± 41 ml/min, P < 0.05) and HR from 76 ± 5 to 97 ± 8 beats/min ( P< 0.05), but did not alter MAP, GFR, or autoregulation of RBF and GFR. Since a number of interactions between ET-1 and the renin-angiotensin system have been reported previously, experiments were repeated during angiotensin converting enzyme (ACE) inhibition by trandolaprilat (2 mg/kg iv). When ETA receptor blockade was combined with ACE inhibition, which by itself had no effects on renal hemodynamics, marked changes were observed: MAP decreased from 91 ± 4 to 80 ± 5 mmHg ( P < 0.05), HR increased from 85 ± 5 to 102 ± 11 beats/min ( P < 0.05), and RBF increased from 278 ± 23 to 412 ± 45 ml/min ( P< 0.05). Despite a pronounced decrease in renal vascular resistance over the entire pressure range investigated (40–100 mmHg), the capacity of the kidneys to autoregulate RBF was not impaired. The GFR remained completely unaffected at all pressure levels. These results demonstrate that endogenously generated ET-1 contributes significantly to renal vascular tone but does not interfere with the mechanisms of renal autoregulation. If ETAreceptors are blocked, then the vasoconstrictor effects of ET-1 in the kidney are compensated for to a large extent by an augmented influence of ANG II. Thus ET-1 and ANG II appear to constitute a major interrelated vasoconstrictor system in the control of RBF.

Renovascular BKCa channels are not activated in vivo under resting conditions and during agonist stimulation

2007 ◽  
Vol 292 (1) ◽  
pp. R345-R353 ◽  
Author(s):  
Linda Magnusson ◽  
Charlotte Mehlin Sorensen ◽  
Thomas Hartig Braunstein ◽  
Niels-Henrik Holstein-Rathlou ◽  
Max Salomonsson
Keyword(s):  
Vascular Tone ◽  
Ang Ii ◽  
Small Reduction ◽  
Bkca Channels ◽  
Agonist Stimulation ◽  
Electromagnetic Flowmetry ◽  
Renal Vascular ◽  
Renal Vascular Tone

We investigated the role of large-conductance Ca2+-activated K+ (BKCa) channels for the basal renal vascular tone in vivo. Furthermore, the possible buffering by BKCa of the vasoconstriction elicited by angiotensin II (ANG II) or norepinephrine (NE) was investigated. The possible activation of renal vascular BKCa channels by cAMP was investigated by infusing forskolin. Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry or ultrasonic Doppler. Renal preinfusion of tetraethylammonium (TEA; 3.0 μmol/min) caused a small reduction of baseline RBF, but iberiotoxin (IBT; 0.3 nmol/min) did not have any effect. Renal injection of ANG II (1–4 ng) or NE (10–40 ng) produced a transient decrease in RBF. These responses were not affected by preinfusion of TEA or IBT. Renal infusion of the BKCa opener NS-1619 (90.0 nmol/min) did not affect basal RBF or the response to NE, but it attenuated the response to ANG II. Coadministration of NS-1619 with TEA or IBT abolished this effect. Forskolin caused renal vasodilation that was not inhibited by IBT. The presence of BKCa channels in the preglomerular vessels was confirmed by immunohistochemistry. Despite their presence, there is no indication for a major role for BKCa channels in the control of basal renal tone in vivo. Furthermore, BKCa channels do not have a buffering effect on the rat renal vascular responses to ANG II and NE. The fact that NS-1619 attenuates the ANG II response indicates that the renal vascular BKCa channels can be activated under certain conditions.

scholarly journals Vestibular stimulation leads to distinct hemodynamic patterning

2000 ◽  
Vol 279 (1) ◽  
pp. R118-R125 ◽  
Author(s):  
I. A. Kerman ◽  
B. A. Emanuel ◽  
B. J. Yates
Keyword(s):  
Vascular Tone ◽  
Systemic Blood Pressure ◽  
Vestibular Stimulation ◽  
Doppler Flowmetry ◽  
Afferent Activation ◽  
Pressor Responses ◽  
Renal Vascular ◽  
Vestibulosympathetic Reflexes ◽  
Renal Vascular Tone ◽  
Stimulation Of

Previous studies demonstrated that responses of a particular sympathetic nerve to vestibular stimulation depend on the type of tissue the nerve innervates as well as its anatomic location. In the present study, we sought to determine whether such precise patterning of vestibulosympathetic reflexes could lead to specific hemodynamic alterations in response to vestibular afferent activation. We simultaneously measured changes in systemic blood pressure and blood flow (with the use of Doppler flowmetry) to the hindlimb (femoral artery), forelimb (brachial artery), and kidney (renal artery) in chloralose-urethane-anesthetized, baroreceptor-denervated cats. Electrical vestibular stimulation led to depressor responses, 8 ± 2 mmHg (mean ± SE) in magnitude, that were accompanied by decreases in femoral vasoconstriction (23 ± 4% decrease in vascular resistance or 36 ± 7% increase in vascular conductance) and increases in brachial vascular tone (resistance increase of 10 ± 6% and conductance decrease of 11 ± 4%). Relatively small changes (<5%) in renal vascular tone were observed. In contrast, electrical stimulation of muscle and cutaneous afferents produced pressor responses (20 ± 6 mmHg) that were accompanied by vasoconstriction in all three beds. These data suggest that vestibular inputs lead to a complex pattern of cardiovascular changes that is distinct from that which occurs in response to activation of other types of somatic afferents.

Inhibition of ROMK blocks macula densa tubuloglomerular feedback yet causes renal vasoconstriction in anesthetized rats

2017 ◽  
Vol 312 (6) ◽  
pp. F1120-F1127 ◽  
Author(s):  
Magali Araujo ◽  
William J. Welch ◽  
Xiaoyan Zhou ◽  
Kathleen Sullivan ◽  
Shawn Walsh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Tubuloglomerular Feedback ◽  
Volume Depletion ◽  
Renal Vasoconstriction ◽  
Compound C ◽  
Altered Blood ◽  
Renal Vascular ◽  
Dose Dependent

The Na+-K+-2Cl− cotransporter (NKCC2) on the loop of Henle is the site of action of furosemide. Because outer medullary potassium channel (ROMK) inhibitors prevent reabsorption by NKCC2, we tested the hypothesis that ROMK inhibition with a novel selective ROMK inhibitor (compound C) blocks tubuloglomerular feedback (TGF) and reduces vascular resistance. Loop perfusion of either ROMK inhibitor or furosemide caused dose-dependent blunting of TGF, but the response to furosemide was 10-fold more sensitive (IC50 = 10−6 M for furosemide and IC50 = 10−5 M for compound C). During systemic infusion, both diuretics inhibited TGF, but ROMK inhibitor was 10-fold more sensitive (compound C: 63% inhibition; furosemide: 32% inhibition). Despite blockade of TGF, 1 h of constant systemic infusion of both diuretics reduced the glomerular filtration rate (GFR) and renal blood flow (RBF) by 40–60% and increased renal vascular resistance (RVR) by 100–200%. Neither diuretic altered blood pressure or hematocrit. Proximal tubule hydrostatic pressures (PPT) increased transiently with both diuretics (compound C: 56% increase; furosemide: 70% increase) but returned to baseline. ROMK inhibitor caused more natriuresis (3,400 vs. 1,600% increase) and calciuresis (1,200 vs. 800% increase) but less kaliuresis (33 vs. 167% increase) than furosemide. In conclusion, blockade of ROMK or Na+-K+-2Cl− transport inhibits TGF yet increases renal vascular resistance. The renal vasoconstriction was independent of volume depletion, blood pressure, TGF, or PPT.

Cyclosporine nephrotoxicity: sodium excretion, autoregulation, and angiotensin II

1987 ◽  
Vol 252 (4) ◽  
pp. F733-F742 ◽  
Author(s):  
F. J. Kaskel ◽  
P. Devarajan ◽  
L. A. Arbeit ◽  
J. S. Partin ◽  
L. C. Moore
Keyword(s):  
Sodium Excretion ◽  
Renin Angiotensin System ◽  
Tubuloglomerular Feedback ◽  
Angiotensin System ◽  
Renal Vasoconstriction ◽  
Fluid Delivery ◽  
Cyclosporine Nephrotoxicity ◽  
Blood Pressures ◽  
Renal Vascular ◽  
Pressure Controlled

Cyclosporine-induced nephrotoxicity (CIN) was studied in rats treated for 7 days with cyclosporine (10 mg x kg-1 x day-1 im) or vehicle (CON). CIN rats displayed characteristic reductions in glomerular filtration (GFR) and renal blood blood flow (RBF), and electron microscopy showed injury to proximal cells. Metabolic studies (7 day) showed significantly lower renal sodium excretion in conscious CIN rats compared with CON. In anesthetized rats at similar blood pressures, nephron GFR (SNGFR) was lower in CIN than CON, but fractional Na reabsorption was similar. In CIN, SNGFR, measured proximally to block flow to the sensing site of tubuloglomerular feedback (TGF) at the macula densa, was not significantly different than distal SNGFR. The rate of distal fluid delivery was significantly lower in CIN than in CON. Inhibition of the renin-angiotensin system (RAS) with captopril (CAP, 10 mg/kg iv), or saralasin (SAR, 0.3 mg x kg-1 x h-1 iv) caused marked arterial hypotension in CIN and a fall in renal vascular resistance (RVR). With arterial pressure controlled, CAP or SAR increased GFR and RBF, and reduced RVR in CIN, but did not reverse the renal deficits compared with similarly treated CON. RBF autoregulation in CIN was impaired between 90 and 140 mmHg but was partially restored by CAP. We conclude that both the filtered load and excretion rate of sodium in CIN are significantly reduced compared with controls, that SNGFR in CIN is not depressed by TGF in response to elevated distal fluid delivery, and that the RAS is not a primarily mediator of the renal vasoconstriction in CIN.

Hemodilution mediates changes in renal hemodynamics after acute volume expansion in rats

1998 ◽  
Vol 274 (6) ◽  
pp. R1670-R1676 ◽  
Author(s):  
Kleber G. Franchini
Keyword(s):  
Volume Expansion ◽  
Vascular Tone ◽  
Renal Perfusion ◽  
Renal Hemodynamics ◽  
Tubuloglomerular Feedback ◽  
Renal Nerves ◽  
Vagus Nerves ◽  
Renal Hemodynamic ◽  
Neural Influences ◽  
Renal Vascular

The present study examined the factors responsible for triggering renal hemodynamic adjustments during acute volume expansion. The renal hemodynamic effects of graded volume expansion with 0.9% saline (Sal; 1, 2, and 4% of body wt), 7% BSA solution (0.35, 0.70, and 1.4% body wt), or whole blood from a donor rat (WBL; 0.35, 0.70, and 1.4% body wt) were compared in rats anesthetized with pentobarbital sodium. Neural influences on the kidney were eliminated by vagus nerves, baro/chemoreceptor afferents, and renal nerves section, and renal perfusion pressure was controlled at constant level (∼120 mmHg) throughout the experiments. In Sal- and BSA-expanded rats, renal blood flow (RBF) increased (Sal: 15, 40, 71%; BSA 17, 49, 107%) and renal vascular resistance (RVR) decreased in parallel with the degree of volume expansion (RVR: Sal 17, 31, 44%; and BSA: 15, 35, 54%). Renal hemodynamics remained unaltered after expansion with WBL. In rats expanded with Sal or BSA, correction of the fall of hematocrit restored RBF and RVR to control levels. Interference with tubuloglomerular feedback by uretheral obstruction had no effect on the decrease in RVR with Sal or BSA. Inhibition of the vascular tone by intrarenal papaverine infusion also did not alter the renal hemodynamic response to volume expansion with Sal or BSA. These findings suggest that the changes in renal hemodynamics after acute expansion are likely mediated by changes in rheologic properties of the blood rather than by changes in active vascular tone.

Effect of P-450 omega-hydroxylase metabolites of arachidonic acid on tubuloglomerular feedback

1994 ◽  
Vol 266 (6) ◽  
pp. F934-F941 ◽  
Author(s):  
A. P. Zou ◽  
J. D. Imig ◽  
P. R. Ortiz de Montellano ◽  
Z. Sui ◽  
J. R. Falck ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Tubuloglomerular Feedback ◽  
Loop Of Henle ◽  
Rate Dependent ◽  
Nephron Segment ◽  
Flow Pressure ◽  
Renal Vascular ◽  
Stop Flow ◽  
Renal Vascular Tone

The role of endogenous P-450 metabolites of arachidonic acid (AA) on the tubuloglomerular feedback (TGF) response was examined. Under control conditions stop-flow pressure (SFP) fell by 17.0 +/- 2.1 mmHg when the perfusion rate of the loop of Henle was increased from 0 to 50 nl/min. Addition of AA (50 microM) to the perfusate lowered basal SFP by 11.4 +/- 1.1 mmHg and potentiated the TGF response. This effect was blocked by addition of a P-450 inhibitor, 17-octadecynoic acid (17-ODYA) (10 microM), to the perfusate. Perfusion of the loop of Henle with 17-ODYA elevated basal SFP by 3.7 +/- 0.3 mmHg and reduced the TGF response by 80%. After blockade of endogenous P-450 activity with 17-ODYA, addition of 20-hydroxyeicosatetraenoic acid (20-HETE, 10 microM) to the perfusate produced a flow rate-dependent fall in SFP. The effect of 20-HETE was not altered by pretreating the animal with meclofenamate (2 mg/kg iv) or by perfusing the nephron segment with furosemide (50 microM). These results indicate that endogenous P-450 metabolites of AA, particularly 20-HETE, may play a role in TGF and the regulation of renal vascular tone.

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