Biomedical subjects

M J Fiksen-Olsen

Publications and source records attributed to M J Fiksen-Olsen.

At least 19 recordsLinked to original sources

PubMed1995

Pressure dependency of canine intrarenal blood flow within the range of autoregulation.

The mechanism of pressure-induced natriuresis remains controversial. To assess whether intracortical or medullary renal blood flows (RBF) change with changes in renal perfusion pressure (RPP), global and regional RBFs were measured using the dynamic spatial reconstructor, a fast computed tomography scanner, in eight anesthetized dogs (group B) within the range of RBF autoregulation (RPP of 153.5 and 114.4 mmHg). Similar measurements were obtained in seven control dogs (group A) in which RPP was not manipulated. In group B, only inner medullary perfusion decreased (from 0.84 to 0.51 ml/min per cm3 of tissue, P = 0.03) with reduction of RPP, whereas global renal, intracortical, and outer medullary perfusions remained unaltered. In group A there was no change in global or regional renal perfusion. The change in inner medullary perfusion in group B (-34.7%) was significantly different (P = 0.021) from that in group A (+27.4%). Global, cortical, and total medullary RBFs (ml/min) and volumes did not change in either group. These results suggest that with changes in RPP, the only detectable change in intrarenal perfusion occurs in the inner medulla.

Animals↗

PubMed1994

Direct measurement of renal medullary blood flow in the dog.

We studied the responses of total renal blood flow (RBF) and renal medullary blood flow (RMBF) to changes in renal perfusion pressure (RPP) within and below the range of renal autoregulation in the anesthetized dog (n = 7). To measure RMBF, we developed a technique in which the medulla is exposed by excising a section of infarcted cortex and a multiple optical fiber flow probe, connected to a laser-Doppler flowmeter, is placed on the medulla. At the baseline RPP of 120 +/- 1 mmHg, RBF was 2.58 +/- 0.33 ml.min-1.g perfused kidney wt-1, and RMBF was 222 +/- 45 perfusion units. RPP was then decreased in consecutive 20-mmHg steps to 39 +/- 1 mmHg. At 80 +/- 1 mmHg, RBF remained at 89 +/- 4% of the baseline value; however, RMBF had decreased significantly (P < 0.05) to 73 +/- 4% of its baseline value. The efficiency of autoregulation of RBF and of RMBF within the RPP range of 120 to 80 mmHg was determined by calculating an autoregulatory index (AI) for each parameter using the formula AI = (%delta blood flow)/(%delta RPP). An AI of 0 indicates perfect autoregulation, and an index of 1 indicates a system with a fixed resistance. The AI for RBF averaged 0.33 +/- 0.12 over this pressure range and showed a significantly greater (P < 0.05) autoregulatory ability than did the RMBF (0.82 +/- 0.13). Decreasing perfusion pressure < 80 mmHg produced significant decreases in both RBF and RMBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Measurement of renal perfusion and blood flow with fast computed tomography.

Fast computed tomography (CT) is one of the few methods available to measure cortical and medullary renal blood flow (RBF) directly. Because these measurements are complicated by passage of the contrast medium into extravascular compartments, we used the residual opacity following the vascular blush as an index to account for extravascular iohexol. Kidneys of anesthetized dogs were examined in situ by fast CT following intra-aortic injections of iohexol. Perfusion was analyzed during a control period and three subsequent periods in which RBF was reduced by 10%, 30%, and 50%. Cortical microvascular distribution volume changed from 19.7 +/- 2.8% to 19.8 +/- 1.7%, 15.3 +/- 1.2%, and 9.9 +/- 1.7%, respectively, without significant alterations in cortical mean transit time. Microvascular distribution volume was divided by mean transit time to determine tissue perfusion. Cortical perfusion changed from 3.8 +/- 0.7 to 3.9 +/- 0.6, 3.1 +/- 0.5, and 2.2 +/- 0.5 mL.min-1.mL tissue-1. Total cortical blood flow (cortical perfusion multiplied by cortical volume) decreased from 164 +/- 32 to 159 +/- 31, 117 +/- 20, and 86 +/- 22 mL/min, respectively. Medullary microvascular distribution volume, mean transit time, perfusion, and total blood flow remained unchanged. Fast CT-determined total RBFs (cortex plus medulla) were similar to simultaneous electromagnetic flow measurements. These results indicate that renal regional perfusion is more dependent on the microvascular distribution volume than mean transit time and that variations in renal tissue perfusion with reduction of RBF are more apparent in the cortex than in the medulla.

Analysis of Variance↗

PubMed1992

Renal kinin antagonism does not impair pressure-induced natriuresis.

We studied the contribution of the renal kallikrein-kinin system to short-term electrolyte and water balance during baseline and during acutely elevated renal perfusion pressure (RPP) in the anesthetized dog. Renal blood flow, glomerular filtration rate, urine flow rate, renin secretion rate, and urinary excretion of sodium, potassium, prostaglandin E2 (PGE2), and kinins were measured at baseline RPP during intrarenal infusion of 0.9% saline or the competitive bradykinin analogue [D-Arg0,Hyp3,Thi5,D-Phe7,Thi8]bradykinin (50 micrograms/min), which blocks vascular and interstitial kinin receptors. RPP was then raised above baseline (control group 25%; kinin analogue group 22%) by ligating the celiac artery, the superior mesenteric artery, and the aorta distal to the renal arteries. Renal parameters were again measured during infusion of saline or the kinin analogue. The analogue had no effect on renal hemodynamic or excretory parameters at baseline perfusion pressures. Increasing RPP significantly increased urine flow rates and urinary sodium excretion rates (control group, 43 mumol/min; kinin analogue group, 55 mumol/min) in both groups of animals. Increasing pressure also tended to decrease renin secretion rate in both groups of animals; however, neither increased pressure nor infusion of the analogue affected urinary excretion of PGE2 or kinins. The results suggest that intrarenal kinins are not powerful short-term regulators of electrolyte and water balance and that an intact kallikrein-kinin system is not necessary to induce pressure diuresis and natriuresis.

Animals↗

PubMed1992

Renal effects of angiotensin II inhibition during increases in renal venous pressure.

Increases in renal venous pressure have been shown to consistently increase renal interstitial pressure; however, not until renal interstitial pressure is increased threefold is a natriuresis noted in normal animals. Since the intrarenal angiotensin II (Ang II) concentration has been postulated to increase with increasing renal venous pressure, the antinatriuretic action of Ang II could override the natriuretic effect of increased renal interstitial pressure. Therefore, the role of Ang II in the natriuretic response to increased renal venous pressure was examined in 10 pentobarbital-anesthetized dogs. Mean arterial pressure, renal blood flow, renal interstitial pressure, glomerular filtration rate, urinary sodium excretion, plasma renin activity, and prostaglandin E2 excretion were measured at renal venous pressures of 3, 15, and 30 mm Hg. The measurements were repeated after the administration of captopril (1 mg/kg i.v. bolus, n = 5) or [Sar1,Ile8]Ang II (50 micrograms/kg i.v. bolus + 50 micrograms/kg/hr infusion, n = 5). Under control conditions, mean arterial pressure, renal blood flow, plasma renin activity, and prostaglandin E2 excretion remained unchanged when renal venous pressure was increased. The elevations in renal venous pressure increased renal interstitial pressure from 7 +/- 2 to 12 +/- 2 and 22 +/- 4 mm Hg, while sodium excretion remained unchanged until renal venous pressure was 30 mm Hg. In the captopril-treated group, increasing renal venous pressure increased renal interstitial pressure as under control conditions; however, sodium excretion (23 +/- 4, 19 +/- 4, and 27 +/- 6 mueq/min) was not significantly increased even at the highest renal venous pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1991

Mediatory role of endothelium-derived nitric oxide in renal vasodilatory and excretory effects of bradykinin.

Intrarenal infusions of 5 ng/kg/min bradykinin (BK) in 5 mg/kg intravenous bolus meclofenamate-treated anesthetized dogs significantly increased renal blood flow, diuresis, natriuresis, and kaliuresis. All these effects were abolished by the simultaneous intrarenal infusion of a competitive inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (LNMMA). Furthermore, the intrarenal infusion of this inhibitor alone also produced a significant decrease in basal renal blood flow. The administration of L-arginine, a precursor of nitric oxide, prevented the inhibitory effect of LNMMA on the renal vasodilatory and excretory response to BK. Glomerular filtration rate and mean arterial pressure did not change throughout the experiment. It is concluded that the renal vasodilatory and excretory responses to intrarenal BK in meclofenamate-treated dogs are largely dependent on endothelium-derived nitric oxide.

Animals↗

PubMed1991

Renal effects of prostaglandin inhibition during increases in renal venous pressure.

The role of prostaglandins (PGs) in mediating the hemodynamic and natriuretic responses to increases in renal interstitial pressure (RIP) induced by altering renal venous pressure (RVP) from control (3.6 +/- 0.6) to 15 and 30 mmHg was examined before and after PG inhibition in pentobarbital sodium-anesthetized dogs. These elevations of RVP resulted in RIP increasing from control (6 +/- 1) to 11 +/- 1 and 23 +/- 2 mmHg, respectively, without altering mean arterial pressure (MAP), renal blood flow (RBF), and glomerular filtration rate (GFR). Sodium excretion increased only when RVP reached 30 mmHg. During the inhibition of PG synthesis, 15 mmHg RVP induced a 10% decrease in RBF, and 30 mmHg RVP induced a further 20% decrease in RBF and a 50% decrease in GFR. PG synthesis inhibition did not alter either the RIP or the sodium excretory response. In conclusion, the natriuresis associated with the RIP increases induced by increasing RVP appears to be independent of PG synthesis. PGs, however, appear to be important for the maintenance of RBF and GFR during increased RVP. These findings suggest that different mechanisms are involved in the hemodynamic and natriuretic responses to arterial vs. venous pressure changes.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

Effect of captopril on renal function in hypertensive dogs with unilateral renal artery stenosis, studied with radionuclide dynamic scintigraphy.

The kidneys of five hypertensive dogs with experimental unilateral renal artery stenosis were examined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 131I-hippuran radionuclide dynamic scintigraphy at 10 and 40 min (respectively) following the administration of intravenous bolus injections of captopril. Doses of 0.2, 0.5, and 1.0 mg/kg captopril reduced mean arterial pressure by 33 +/- 4, 31 +/- 7, and 51 +/- 4 mm Hg and increased plasma renin activity by 40.1 +/- 9.8, 57.6 +/- 3.2, and 34.4 +/- 15.2 ng A1/mL/h, respectively. The time-activity curves of both 99mTc-DTPA and 131I-hippuran indicated that renal excretory function in the stenotic kidney was compromised with all three doses of captopril. However, if nitroprusside was used to reduce the mean arterial pressure to a level comparable to that with captopril, there was no appreciable increase in plasma renin activity and renal excretory function was only partially affected in the stenotic kidney. One hour after the administration of 0.5 mg/kg captopril, the function of the stenotic kidneys was partially restored and, by two hours, the time-activity curves were comparable to control scans. These data demonstrate a reversible, time-limited suppression of stenotic kidney function by captopril in renovascular hypertension and provide support for the use of captopril in the diagnosis of renovascular hypertension by radionuclide dynamic scintigraphy.

Animals↗

PubMed1990

Role of prostaglandins in the renal response to calcium infusion.

The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca.kg-1.min-1) on renal hemodynamics and on renal excretory function were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 min each (1 ml/min). In a second group, the same doses were administered 30 min after the start of an infusion of prostaglandin (PG) inhibitors (intrarenal indomethacin, 10 micrograms.kg-1.min-1, or intravenous bolus injection of meclofenamate, 5 mg/kg). No change with physiological significance was observed during the infusion of 10 micrograms Ca.kg-1.min-1. However, the infusion of 100 micrograms Ca.kg-1.min-1 induced increases (P less than 0.05) in glomerular filtration rate (50%), sodium excretion rate (180%), and fractional excretion of sodium (160%), with respect to control precalcium values. All these changes were prevented by the concurrent administration of PG synthesis inhibitors. Urinary PGE2 and 6-keto-PGF1 alpha increased 220 and 85%, respectively, during the infusion of 100 micrograms Ca.kg-1.min-1, but both decreased (P less than 0.05) below basal levels during the concurrent administration of PG synthesis inhibitors. The infusion of 100 micrograms Ca.kg-1.min-1 decreased (P less than 0.05) renal blood flow by 16% during the administration of PG synthesis inhibitors. These results suggest that PGs are mediating the increase in hemodynamic and excretory factors induced by the intrarenal infusion of 100 micrograms Ca.kg-1.min-1.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

Distribution of prostaglandins E2 and 6-keto-F1 alpha production in dog kidneys.

Little is known about the distribution of prostaglandin E2 (PGE2) and prostacyclin (PGI2) production in the canine kidney. To determine the basal and stimulated profiles of PGE2 and PGI2 production along the corticomedullary axis of the dog kidney, a slice (0.5 mm thick, 10-50 mg) was obtained from six equally spaced zones along the axis (zone 1, medullary crest; zones 2 and 3, inner medulla; zone 4, outer medulla; and zones 5 and 6, cortex) and was divided into equal halves. One half of the slice was incubated with Krebs-Ringer buffer containing arachidonic acid (6.6 x 10(-4) M), bradykinin (9.4 x 10(-6) M), or indomethacin (10(-5) M), whereas the remaining half of each slice was similarly incubated in Krebs-Ringer buffer alone. The production of PGE2 and 6-keto-PGF1 alpha (the stable metabolite of PGI2) was determined by radioimmunoassay. Under basal conditions, both PGE2 and 6-keto-PGF1 alpha were highest in the innermost zones of the inner medulla (PGE2, 3,328 +/- 549 pg/mg; 6-keto-PGF 1 alpha, 1,611 +/- 129 pg/mg) and decreased exponentially to low levels in the cortex (PGE2, undetectable; 6-keto-PGF1 alpha, 13 +/- 2 pg/mg); this production was inhibited by indomethacin. Arachidonic acid significantly increased the production of PGE2 in all zones of the kidney and the production of 6-keto-PGF1 alpha only in zones 3-6.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1990

Stimulation of renin release by intrarenal calcium infusion.

The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca/kg/min) on renin secretion were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 minutes each (1 ml/min). In a second group, the same doses were administered 30 minutes after the start of infusion of prostaglandin synthesis inhibitors (indomethacin 10 micrograms/kg/min intrarenal or injection of meclofenamate 5 mg/kg i.v. bolus). Mean arterial pressure, renal blood flow, and glomerular filtration rate remained unchanged during the infusion of calcium in both groups. The infusion of 10 micrograms Ca/kg/min increased renin secretion 77% and sodium excretion 123%. During the infusion of 100 micrograms Ca/kg/min, renin secretion was not different from precalcium values, whereas urinary 6-keto-PGF1 alpha, urine flow, sodium, potassium, and calcium excretion rates were increased (p less than 0.05). During the administration of prostaglandin synthesis inhibitors, the urinary 6-keto-PGF1 alpha levels were reduced, and the infusion of 10 micrograms Ca/kg/min failed to increase renin secretion, sodium excretion, or 6-keto-PGF1 alpha excretion rates. The infusion of 100 micrograms Ca/kg/min during prostaglandin synthesis inhibition did not modify urine flow or sodium excretion; however, potassium and calcium excretions increased. It is concluded that 1) the intrarenal infusion of small doses of calcium gluconate is capable of stimulating renin secretion through a prostaglandin-mediated mechanism, and 2) the stimulation of renin secretion as well as the increase in sodium excretion induced by calcium are independent of hemodynamic alterations.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

Effects of NG-monomethyl-L-arginine and L-arginine on acetylcholine renal response.

Intrarenal infusion of acetylcholine in meclofenamate-treated dogs significantly increased renal blood flow, diuresis, and natriuresis. Intrarenal infusions of either NG-monomethyl-L-arginine (inhibitor of endothelium-derived relaxing factor formation), or L-arginine (precursor of endothelium-derived relaxing factor formation) did not modify basal levels of those parameters. However, the infusion of NG-monomethyl-L-arginine inhibited the acetylcholine-induced increases in renal blood flow and diuresis without affecting natriuresis, which increased significantly. The infusion of L-arginine failed to further enhance hemodynamic and excretory effects elicited by acetylcholine. The concomitant infusion of L-arginine and NG-monomethyl-L-arginine did not change renal blood flow, urine flow, or sodium excretion rate. L-Arginine administration prevented the inhibitory effect of NG-monomethyl-L-arginine on acetylcholine-induced renal vasodilatation and diuresis. Glomerular filtration rate and mean arterial pressure did not change throughout the experiment. The results indicate that the vasodilatory and diuretic responses to intrarenal acetylcholine in meclofenamate-treated dogs are largely dependent on endothelium-derived relaxing factor.

Acetylcholine↗

PubMed1989

Effect of atriopeptin II on contrast medium-induced changes in renal blood flow.

Volume expansion has been shown to attenuate the vaso-constrictive effects of contrast medium. Since endogenous circulating levels of atrial natriuretic peptides are elevated during volume expansion and since atrial natriuretic peptides have been shown to blunt or block the vasoconstrictive effects of various pharmacologic agents, we examined the effect of atriopeptin II infusion on contrast medium-induced alterations in renal blood flow. Transient changes in renal blood flow were measured with an electromagnetic flow probe following bolus injections of the contrast medium, sodium meglumine diatrizoate (Renovist II, 2 ml/4 sec), into the renal arteries of dogs. Under control conditions (that is, saline vehicle), the bolus of contrast medium caused an initial 15 to 21% increase in renal blood flow at 14 to 21 seconds, followed by a subsequent 5 to 13% decrease in renal blood flow at 43 to 59 seconds after injection. Infusion of atriopeptin II (0.05 pg/kg/min) into the renal artery did not alter arterial blood pressure, glomerular filtration rate, or baseline renal blood flow, but did produce increases in urine flow rate and clearance of sodium. The infusion of atriopeptin II attenuated the contrast medium-induced reduction in RBF, but the infusion of a threshold dose of bradykinin (1 ng/kg/min) had no effect. These results suggest that low doses of atriopeptin II can selectively attenuate the vasoconstrictive effects of contrast medium on renal blood flow without influencing systemic hemodynamics.

Animals↗

PubMed1989

Effects of atrial natriuretic peptide on renal medullary prostaglandin E2 production.

Like arachidonic acid (AA) and bradykinin (BK), the intrarenal administration of atrial natriuretic peptide (ANP) has been shown to increase the urinary excretion of prostaglandin E2 (PGE2). In the present study, the direct in vitro effects of ANP on PGE2 production were compared with those of AA and BK. Canine renal inner medullary slices were preincubated for 30 min and washed in aerated Krebs-Ringer buffer (37 degrees C). During the final incubation period, with the use of varied concentrations of AA, BK, or ANP in Krebs-Ringer buffer, samples were obtained at 0 and 30 min to be used for radioimmunoassay of PGE2. Although the rate of PGE2 production was significantly increased 11-fold with AA and threefold with BK, it was unaffected by four different doses of ANP (10(-5) to 10(-11) M). Furthermore, the production of PGE2 during basal and stimulated (BK or AA) conditions was significantly blocked by indomethacin but not by ANP. These results indicate that ANP had no direct stimulatory or inhibitory effect on the medullary production of PGE2.

Animals↗

PubMed1988

Comparison of the effects of calcium antagonists and converting enzyme inhibitors on renal function under normal and hypertensive conditions.

Calcium antagonists decrease the ability of the kidney to autoregulate renal blood flow (RBF) and glomerular filtration rate (GFR). Therefore, when afferent renovascular resistance is elevated, as in essential hypertension, there is a resultant increase in RBF and GFR with the administration of calcium antagonists. These agents also induce a marked natriuresis because of direct tubular action through unknown mechanisms. The natriuresis can be dissociated from renal and systemic hemodynamic actions, indicating that the decreased sodium reabsorption could override other compensatory mechanisms explaining the absence of sodium retention during the treatment. The renal effects of converting enzyme inhibitors (CEIs) can be explained by the reduction of intrarenal formation in angiotensin II. Because the activation of the renin-angiotensin system is mainly responsible for inducing sodium retention during a decrease in systemic blood pressure, CEIs could have a protecting effect without disturbing other homeostatic mechanisms. CEIs decrease efferent glomerular resistance, reducing capillary pressure and thereby reducing GFR. This effect is not translated in sodium retention because the reduction of GFR is mild during captopril administration in kidneys with normal or increased renal perfusion pressure. At low renal perfusion pressure, the reduced glomerular afferent vasoconstriction can compromise GFR, leading to renal insufficiency. Although these situations are not likely to be encountered during the treatment of uncomplicated essential hypertension, in severe hypertension with hypertrophy of pre-glomerular vessels, glomerular perfusion may decrease. Combination therapy of calcium antagonists and CEIs has been reported to be an effective treatment of severe hypertension. Currently, little information is available on the manner in which renal function is affected by simultaneous administration of both drugs.

Angiotensin II↗

PubMed1988

Three-dimensional canine renovascular structure and circulation visualized in situ with the dynamic spatial reconstructor.

The dynamic spatial reconstructor--a unique, high speed, volume-scanning, X-ray computed tomographic imaging system--was utilized to examine canine renovascular anatomy and renal circulation in situ. In each of the four kidneys examined in this study initial scans were done during bolus injections of angiographic contrast material into the renal artery. A subsequent scan was then performed following an injection of methyl-methacrylate-based casting compound that had been contrast enhanced with ethiodol. After the scans, each kidney was removed, and its parenchyma was digested in potassium hydroxide to expose the vascular cast. Comparison of casts with their reconstructed images and with images obtained during injection of contrast material showed that interlobar arteries and occasionally arcuate arteries could be clearly detected. Although discrete vessels less than 1 mm in diameter could not be resolved, dynamic changes in parenchymal distribution of density during passage of contrast material allowed interpretation of flow through the multiple capillary beds of the kidney. Such analysis indicated that maximal density was in the outer-middle zone of the cortex throughout the duration of the scan. Analysis of artery-to-vein transit time showed arrival of contrast material in the renal vein as soon as 3 sec, and continuation for longer than 8 sec, after the renal artery bolus. In conclusion, renal circulation in the dog can be discretely visualized with the dynamic spatial reconstructor up to the level of the arcuate arteries; however, capillary flow as a whole can be followed through the cortex, and the results suggest the presence of both rapid and slow components of peritubular circulation.

Animals↗

PubMed1988

Role of prostaglandins in mediating the renal effects of atrial natriuretic factor.

The natriuretic response to the intrarenal administration of atrial natriuretic factor (ANF) is accompanied by an increase in the synthesis of prostaglandins and by a redistribution of renal blood flow from the superficial to the deep cortex. This study was undertaken to define whether prostaglandins mediate the ANF-induced redistribution of renal blood flow and if prostaglandins and renal blood flow redistribution contribute to the natriuretic actions of ANF. In anesthetized dogs, the intrarenal administration of indomethacin (10 micrograms/kg/min) or the intravenous administration of meclofenamate (5 mg/kg) completely prevented the sixfold and twofold increments in urinary prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, respectively; it also abolished the redistribution of renal blood flow to the deep cortex. However, ANF induced a similar natriuresis before (from 53 +/- 17 to 281 +/- 48 microEq/min) and after (from 45 +/- 13 to 273 +/- 60 microEq/min) the administration of prostaglandin synthesis inhibitors. It is concluded that the ANF-induced redistribution of renal blood flow to the deep cortex is prostaglandin-mediated but that neither redistribution nor increased prostaglandin synthesis is an important mediator of ANF's natriuretic action.

6-Ketoprostaglandin F1 alpha↗

PubMed1987

Role of prostaglandins in the cortical distribution of renal blood flow following reductions in renal perfusion pressure.

The purpose of this study was to examine the role of prostaglandins in the redistribution of renal cortical blood flow that occurs following reductions in renal perfusion pressure. The distribution of blood flow to the renal cortex was examined using radio-labeled microspheres (15 +/- 1 micron). It was found that in animals not treated with a prostaglandin synthesis inhibitor a decrease in renal perfusion pressure to the limit of renal blood flow autoregulation was associated with a decrease in fractional flow to the outer cortex (Zone I) and an increase in fractional flow to the inner cortex (Zones III and IV). A further decrease in renal perfusion pressure below the limit of autoregulation produced a further decrease in the fractional flow to Zone I and a further increase in fractional flow to Zones III and IV. In contrast, in animals treated with the prostaglandin synthesis inhibitor meclofenamate (5 mg/kg, i.v. bolus) a reduction in renal perfusion pressure to the limit of renal blood flow autoregulation produced no change in fractional blood flow to any of the 4 cortical zones. A further decrease in renal perfusion pressure, however, did produce a fall in fractional blood flow to Zone I and an increase in fractional flow to Zones III and IV. In conclusion, the results of this study indicate that within, but not below, the limit of renal blood flow autoregulation prostaglandin synthesis is an important factor in the regulation of renal cortical blood flow distribution.

Animals↗