Oxygen-radical regulation of renal blood flow following suprarenal aortic clamping

OBJECTIVE: Renal insufficiency continues to be complication that can affect patients after treatment for suprarenal aneurysms and renal artery occlusive disease. One proposed mechanism of renal injury after suprarenal aortic clamping (above the superior mesenteric artery) and reperfusion (SMA-SRACR) is the loss of microvascular renal blood flow with subsequent loss of renal function. This study examines the hypothesis that the loss of medullary and cortical microvascular blood flow following SMA-SRACR is due to oxygen-derived free radical down-regulation of endogenous medullary and cortical nitric oxide synthesis. METHODS: Anesthetized male Sprague-Dawley rats (about 350 g) either had microdialysis probes or laser Doppler fibers inserted into the renal cortex (depth of 2 mm) and into the renal medulla (depth of 4 mm). Laser Doppler blood flow was continuously monitored. The microdialysis probes were connected to a syringe pump and perfused in vivo at 3 microL/min with lactated Ringer's solution. The animals were subjected to SMA-SRACR (or sham) for 30 minutes, followed by 60 minutes of reperfusion. Laser Doppler blood flow after the 30 minutes of SMA-SRACR followed by 60 minutes of reperfusion was compared with the time zero (basal) and with the corresponding sham group and reported as percent change compared with the time zero baseline. The microdialysis fluid was collected at time zero (basal) and compared with the dialysis fluid collected after 30 minutes of SMA-SRACR followed by 60 minutes of reperfusion as well as the corresponding sham group. The microdialysis dialysate was analyzed for total nitric oxide (microM) and prostaglandin E2 (PGE2), 6-keto-PGF(1alpha) (PGI2 metabolite), and thromboxane B2 synthesis. The data are reported as percent change compared with the baseline time zero. The laser Doppler blood flow and microdialysis groups were treated with either saline carrier, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (30 mg/kg, nitric oxide synthesis inhibitor), L-arginine (400 mg/kg, nitric oxide precursor), superoxide dismutase (SOD, 10,000 U/kg, oxygen-derived free radical scavenger), L-NAME + SOD, or L-arginine + SOD. SOD was given 30 minutes before the reperfusion, and the other drugs were given 15 minutes before reperfusion. The renal cortex and medulla were separated and analyzed for inducible nitric oxide synthase (iNOS), cyclooxygenase-2, prostacyclin synthase, and PGE2 synthase content by Western blot. RESULTS: Superior mesenteric artery-SRACR caused a marked decrease in medullary and cortical blood flow with a concomitant decrease in endogenous medullary and cortical nitric oxide synthesis. These changes were further accentuated by L-NAME treatment but restored toward sham levels by L-arginine treatment after SMA-SRACR. The kidney appeared to compensate for these changes by increasing cortical and medullary PGE2 synthesis and release. SOD treatment restored renal cortical and medullary nitric oxide synthesis and blood flow in the ischemia-reperfusion group and in the ischemia-reperfusion group treated with L-NAME. CONCLUSIONS: These data show that nitric oxide is important in maintaining renal cortical and medullary blood flow and nitric oxide synthesis. These data also support the hypothesis that the loss of medullary and cortical microvascular blood flow following SRACR is due in part to oxygen-derived free radical downregulation of endogenous medullary and cortical nitric oxide synthesis.     

Muscle blood flow after amputation: Increased flow with medullary plugging

At below-knee amputation for arterial insufficiency in 31 patients, the muscle blood flow of quadriceps and triceps surae was measured by clearance of ^99mTc pertechnetate pre-and postoperatively. In 15 patients, myoplastic amputation was performed and in 16 patients the medullary cavity of the tibial stump was plugged with cortex of the removed bone as well. Plugging caused a two-third increase in muscle blood flow.     

Muscle blood flow after amputation: Increased flow with medullary plugging

At below-knee amputation for arterial insufficiency in 31 patients, the muscle blood flow of quadriceps and triceps surae was measured by clearance of ^99mTc pertechnetate pre-and postoperatively. In 15 patients, myoplastic amputation was performed and in 16 patients the medullary cavity of the tibial stump was plugged with cortex of the removed bone as well. Plugging caused a two-third increase in muscle blood flow.     

Muscle blood flow after amputation. Increased flow with medullary plugging

At below-knee amputation for arterial insufficiency in 31 patients, the muscle blood flow of quadriceps and triceps surae was measured by clearance of 99mTc pertechnetate pre- and postoperatively. In 15 patients, myoplastic amputation was performed and in 16 patients the medullary cavity of the tibial stump was plugged with cortex of the removed bone as well. Plugging caused a two-third increase in muscle blood flow.     

The effects of ketamine and innovar on the renal cortical and medullary blood flow of the dog.

To study the effects of Ketamine and Innovar on renal function, the renal cortical and medullary blood flows of dog were measured using a thermo-electrical flowmeter, along with the urine output, blood pressure and pulse rate. Ketamine decreased the renal cortical blood flow and the urine output. Innovar increased the renal cortical blood flow, but did not alter the medullary blood flow appreciably, and decreased the urine output. Neither of these variations in renal blood flows ran parallel with variations in the arterial pressure nor did variations in the urine output run parallel with those in the blood flows. All anaesthetic agents are inhibitory to kidney, but Innovar may be preferred to other anaesthetics in view of the finding that the renal blood flows are well maintained even under anaesthesia with this agent.     

Effects of nifedipine on renal cortical and medullary blood flow in two-kidney, one-clip renovascular hypertension in rabbits

The effects of nifedipine, a calcium antagonist, on blood pressure and renal regional blood flow were investigated in two-kidney, one-clip renovascular hypertensive rabbits. At 1 week after left renal artery constriction, in the constricted group, systemic blood pressure (BP) significantly rose with the elevation of plasma renin activity (PRA). In both kidneys, renal vascular resistance (RVR on the constricted group was significantly increased as compared to that in the control group. In the clipped kidney, total renal blood flow (RBF) and renal cortical blood flow (RCBF) of the constricted group were significantly decreased, while renal medullary blood flow (RMBF) remained at the control value. In the nonclipped kidney, RBF and RCBF of the constricted group did not significantly change, and RMBF was significantly increased as compared to that of the control group. After administration of nifedipine for 1 week (1.0 mg/kg/day), BP in the constricted group was decreased to the control level and PRA in both groups was increased. The percent change of BP in the constricted group was significantly decreased and the percent change of PRA in the constricted group was significantly increased as compared to those in the control group. Nifedipine increased RBF, RCBF and RMBF and decreased RVR of both kidneys in each group. In the nonclipped kidney, the percent change of RBF, RCBF and RMBF of the constricted group was significantly increased and the percent change of RVR was significantly decreased as compared to those of the control group. In the clipped kidney, only the percent change of RBF of the constricted group was significantly lower than that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Methods of renal blood flow measurement

Variations in regional renal blood flow have been implicated in a variety of disease states. Many techniques have been developed in an attempt to accurately assess these changes. The microsphere technique is the most widely used method at the present time. This technique allows focal measurements to be performed, but there is a conflict between the resolution of the method and the number of microspheres necessary in each sample. New imaging techniques such as tomography and autoradiography enable visual assessment of renal blood flow. Though there is no ideal method, these techniques have opended up new possibilities in the quantification of regional renal blood flow.     

Renal medullary infusion of indomethacin and adenosine. Effects on local blood flow, tissue ion content and renal excretion

Perfusion of the renal medulla and osmotic hypertonicity of its interstitium are the two important features of this zone which can influence body fluid homeostasis, especially arterial blood pressure. Separate manipulation of the two variables is best obtained with the intramedullary infusion of active agents. In this study, a set-up combining the possibility of infusion into the medulla with measurement of local blood flow (MBF, laser-Doppler flux) and extracellular ion concentration (tissue electrical admittance, Y) was used to determine effects of intramedullary indomethacin (Indo) and adenosine (Ado) in anaesthetized rats. Intramedullary Indo, 1 mg kg(-1 )h(-1), significantly increased tissue Y, by 12 +/- 3%, and significantly decreased MBF by 20 +/- 3%. There was also an unexplained increase of sodium excretion (U(Na)V) by 169 +/- 24% and of urine flow (V) by 62 +/- 6% (n = 10, both p < 0.03). Intramedullary Ado, 5 microg kg(-1) h(-1), did not alter Y, MBF or U(Na)V, whereas V increased 45 +/- 6% and urine osmolality decreased 25 +/- 4% (both changes significant). Elevation of medullary interstitial Ado to a level that did not alter MBF or U(Na)V induced a moderate defect of urine concentration that was not due to a decrease in ionic medullary hypertonicity.     

Multiple medullary venous malformations decreasing cerebral blood flow: case report

A rare case of multiple medullary venous malformations in the right cerebral hemisphere is reported. The literature review yielded only one case of multiple medullary venous malformations. Computed tomography scan showed multiple calcified lesions with linear contrast enhancement representing abnormal dilated vessels and mild atrophic change of the right cerebral hemisphere. Single-photon emission computed tomography using N-isopropyl-p-(123I) iodoamphetamine demonstrated decreased cerebral blood flow in the right cerebral hemisphere.     

Role of countercurrent multiplication in renal ammonium handling: regulation of medullary ammonium accumulation

Ammonium (NH3 plus NH4+), produced predominantly in the proximal tubule, is transferred to the final urine by a process involving countercurrent multiplication of ammonium which generates an ammonium concentration gradient in the renal medulla. It was hypothesized that if urinary ammonium excretion rates are controlled in part by the medullary ammonium gradient, changes in hydration and acid-base state should cause changes in the medullary ammonium gradient consistent with expected changes in urinary ammonium concentrations. To test that hypothesis, rats were subjected to water diuresis, water deprivation, water deprivation plus furosemide, and dietary acid and base loads and corticomedullary ammonium gradients in their kidneys were then measured. Sections were cut along the corticomedullary axis to yield slices of cortex, outer stripe of outer medulla, inner stripe of outer medulla, and three levels of the inner medulla. The total ammonia content of homogenized slices was measured by either a membrane ammonia electrode or an enzymatic technique. Kidneys from water-deprived animals showed a distinct ammonium gradient along the corticomedullary axis, with the highest contents found at the tip of the papilla. The gradient was attenuated by water diuresis and abolished by furosemide. Acid loading enhanced the gradient, and base loading abolished it. These results indicate that the corticomedullary ammonium gradient is regulated in response to changes in hydration and acid-base state.     

Effects of chronic cyclosporine administration on renal blood flow and intrarenal blood flow distribution

Cyclosporine-induced decreases in renal blood flow (RBF) and glomerular function are well documented. Glomerular filtration and tubular function may be affected by changes in both total renal blood flow and cortical blood flow distribution (CBFD). The effect of CsA on RBF, CBFD, glomerular filtration rate, and tubular function was studied in conscious ewes receiving a mean CsA dose of 30 mg/kg/day for 28 days with mean CsA trough levels of 344 +/- 45 ng/ml. RBF and CBFD were determined by the injection of 15 microns radioactive microspheres before and after one month of treatment with CsA or its vehicle, olive oil. RBF decreased by 24% from 7.65 +/- 0.87 to 5.79 +/- 0.42 ml/min/g of kidney in CsA-treated ewes (P = 0.014), while no decrease was noted in the control group (7.92 +/- 1.10 vs. 7.62 +/- 0.71). Intracortical blood flow decreased in proportion to the fall in total renal blood flow--thus CsA treatment did not change the cortical distribution of flow. There was a 25% decrease in GFR, as determined by inulin clearance, in the CsA-treated group (80 +/- 6 vs. 62 +/- 3 ml/min; P = 0.027) while there was a nonsignificant increase in control animals (62 +/- 11 vs. 92 +/- 7 ml/min). There was no evidence of tubular dysfunction in either group. There were also no changes in urinary excretion rates of prostaglandins PGE2, 6-keto-PGF1 alpha or thromboxane B2, nor were there changes in plasma renin activity. CsA induced decreases in RBF occur red without redistribution of cortical blood flow, indicating that altered cortical distribution of blood flow is not responsible for the changes in GFR or tubular function that have been reported. The changes in renal blood flow and glomerular filtration rate are independent of changes in renal prostaglandin production, and are likely not associated with altered plasma renin activity.     

Human renal allograft blood flow and early renal function.

Renal allograft blood flow (RBF) was measured at operation by electromagnetic flow meter and probes in 45 patients (34 cadaver donors and 11 living related donors). Mean RBF in 26 patients without acute tubular necrosis (ATN), was 412 +/- 80 ml/min and in 19 patients with ATN, 270 +/- 100 ml/min (p less than .001). Only two of 24 transplants (8%) with RBF greater than 350 ml/min had ATN; whereas, 17 of 21 transplants (81 per cent) with RBF less than 350 ml/min had ATN (p less than .001). In cadaver donor transplants, RBF did not correlate with duration of ATN, warm ischemia time, total ischemia time, pulsatile perfusion time or renal vascular resistance during perfusion. Measurement of renal allograft blood flow can predict presence or absence of postoperative ATN in 87% of patients.     

Sodium nitroprusside-induced hypotension and renal blood flow

Hypotension produced by sodium nitroprusside during halothane anaesthesia in a series of experiments in dogs was accompanied by the maintenance of renal blood flow. Renal blood flow was maintained at levels of systemic pressure at which flow is customarily reduced in man and experimental animals. The significance of this observation is the possibility that sodium nitroprusside has a protective effect on the kidney, not only in states of deliberate hypotension, but in other low flow states where renal perfusion and function may be compromised.