Characterization of the hemodynamic activities of fenoldopam and its enantiomers in the dog

Fenoldopam (SK&F 82526) is a potent and selective dopamine DA-1 agonist with demonstrated renal vasodilator and antihypertensive activities in experimental animals and humans. Fenoldopam is a racemic mixture of two enantiomers, SK&F R-82526 and SK&F S-82526. The R-enantiomer is uniformly reported to be more potent than the racemate; in contrast, there is controversy regarding potency of the S-enantiomer. In these studies, the renal and systemic hemodynamic activities of fenoldopam and its enantiomers are characterized in anesthetized, phenoxybenzamine-treated dogs. The results show that the renal and systemic vasodilator activities of fenoldopam are properties of the R-enantiomer; the S-enantiomer is essentially inactive. The renal and systemic vasodilator properties of SK&F R-82526 are antagonized in a competitive fashion by the DA-1 antagonist, SK&F R-83566, but not the DA-2 antagonist, domperidone. Ganglionic blockade did not attenuate renal vasodilation associated with SK&F R-82526. Thus, the mechanism of SK&F R-82526-associated vasodilation, like that previously established for fenoldopam, is via stimulation of postganglionic DA-1 receptors.     

Renal effects of SK&F 82526 in anesthetized rats

Dopamine affects renal hemodynamics, renal tubular functions, and the secretion of renin. We have studied the renal effects of SK&F 82526 (an agonist which is selective for the DA1 subclass of dopamine receptors) in anesthetized rats. Infused intravenously at 0.005 mumol/min/kg, this drug increased renal plasma flow and the clearances of PAH and insulin, effects which are consistent with decreased renovascular resistance. Concomitantly, urine flow and K excretion increased, and Na excretion tended to increase. All these effects of SK&F 82526 were antagonized by intravenous metoclopramide (1 mumol/min/kg). Despite its diuretic effect and despite its lack of effect on arterial blood pressure, SK&F 82526 increased arterial plasma renin concentration, suggesting a stimulatory effect on renin secretory rate. Taken together, our results demonstrate that the renal effects of SK&F 82526 mimic those of dopamine.     

Effect of felodipine on renal hemodynamics and excretion in the dog

The effects of felodipine on renal hemodynamics and excretion were evaluated in the anesthetized dog. Unilateral renal arterial infusion of felodipine produced ipsilateral increases in the absolute and fractional excretion of sodium and water which were greater than those of potassium; these effects occurred in the absence of changes in mean arterial pressure, renal blood flow, or glomerular filtration rate. There were no significant effects on renal hemodynamic or excretory function in the contralateral kidney. The unilateral renal arterial infusion of isotonic saline or vehicle produced no significant effects on renal hemodynamic or excretory function in either ipsilateral or contralateral kidney. Felodipine, a calcium antagonist with vasodilator antihypertensive properties, in doses which do not affect systemic or renal hemodynamics in the dog, increased urinary flow rate and sodium excretion by decreasing renal tubular water and sodium reabsorption. As a vasodilator antihypertensive agent, felodipine possesses potentially advantageous diuretic and natriuretic properties.     

Effect of meclofenamate on renal vascular resistance in early Goldblatt hypertension in conscious and anesthetized dog

Blood pressure and renal blood flow were monitored in conscious normotensive (N) and 2-kidney Goldblatt hypertensive (H) dogs. Plasma renin activity was significantly increased 4–8 days after partial renal artery occlusion. At this time intravenous administration of meclofenamate, 5 mg/kg, had no effect on blood pressure in the N or H or on renal vascular resistance in the N or in the H (contralateral kidney). The renal vasoconstrictor response to angiotensin II was increased in duration by meclofenamate in both the N and H. In contrast to the absence of an effect of meclofenamate on renal vascular resistance in the conscious dog, the synthesis inhibitor caused a consistent increase in RVR in the N and H when they were anesthetized in the terminal experiment. These results suggest the lack of an influence of prostaglandins on renal vascular resistance in the unaffected kidney in Goldblatt hypertension.     

Fucoidan improves the renal blood flow in the early stage of renal ischemia/reperfusion injury in the rat.

It has been shown that monoclonal anti-P-selectin antibody administration protects renal function in an ischemic model of acute renal failure. This study was designed to evaluate the effect of administration of fucoidan, P-selectin inhibitor, on reduction in renal blood flow induced by ischemia/reperfusion injury in the rat. Experiments were performed on male Wistar rats weighting 35-400 g. The systemic blood pressure (mm Hg) (BP) and renal blood flow (RBF) were monitored continuously and renal vascular resistance (RVR) was calculated. After 20 min period of stabilization animals (6 rats in each group) received one of the following agents administered by continuous i.v. infusion during 165 min: 1 mg/kg of body weight of fucoidan (F1), 10 mg/kg of fucoidan (F10), 100 mg/kg of fucoidan (F100), 10 mg/kg of heparin (H), or 0.9% NaCl solution (control). After 15 min of drug administration the renal vessels of the both kidney were occluded with vascular clamps for 60 min. There were no significant changes in the initial values of RBF, RVR and BP between groups. None procedure affected significantly BP during all experiments. In F10 RBF returned to the initial values in 70th min of reperfusion and did not change up to 90th min. This value was significantly higher than respective value in the control group. In F1 group RBF in 90th min was also higher than in the control group, but it was not statistically significant. The dose of heparine and fucoidan used in the H and F100 groups failed to preserve RBF during reperfusion. In the present study we found that administration of fucoidan--P-selectin inhibitor, increases significantly postischemic renal blood flow and may have renoprotective activity.     

Vasorelaxant effect of C16-PAF and C18-PAF on renal blood flow and systemic blood pressure in the anesthetized rat

The renal vasoactive and systemic hypotensive effects of platelet activating factor (C16:0-PAF and C18:1-PAF) were examined in anesthetized male Wistar rats. Bolus injections of C16-PAF (0.5-25 ng/kg) and C18-PAF (2.5-200 ng/kg) into the arterial circulation of the kidney produced increases in renal blood flow (6-15%) before causing dose-dependent systemic hypotension (2-64 mmHg). The dose-response curves for renal blood flow and systemic blood pressure generated by intrarenal C18-PAF administration were approximately 7 fold to the right of the dose-response curves generated by C16-DPAF. Intrarenal injections of vehicle or the biologically inactive enantiomer C16-DPAF (25-200 ng/kg) did not affect renal blood flow or systemic blood pressure. These results suggest that C16:0-PAF is a more potent renal vasodilator and hypotensive lipid than C18:1-PAF.     

Effect of lysophosphatidylcholine on renal hemodynamics and excretory function in anesthetized rats.

The effect of myristoyl-lysophosphatidylcholine (myristoyl-LPC) on renal hemodynamics, electrolyte and water excretion was examined over a 90 min period in sodium pentobarbital anesthetized male Sprague Dawley rats. Intravenous infusion of myristoyl-LPC at 13 +/- 3 pmol/min resulted in a small fall in systemic blood pressure, a 13% decrease in renal plasma flow without significantly altering glomerular filtration rate and produced a slightly greater excretion of sodium and water than vehicle controls. These results suggest that short term myristoyl-LPC administration can significantly alter renal function producing a weak natriuresis and diuresis which is not dependent on systemic blood pressure and renal hemodynamic changes.     

The role of beta 2-adrenergic vascular receptors in the peripheral vasodilation caused by 17 beta-estradiol in anesthetized pigs

It has been previously shown in anesthetized pigs that intravenous infusion of 2 microg/h of 17beta-estradiol primarily dilated renal, iliac and coronary circulations, while higher doses of the hormone were required to cause vasodilation also in the mesenteric vascular bed. In the same experimental model, a tonic beta2-adrenoceptor mediated vasodilation, which could be argued to attenuate the vasodilator effect of 17beta-estradiol, has been described. The present study was planned to investigate the role of beta2-adrenergic receptors in the hemodynamic responses of renal and mesenteric vascular beds to 17beta-estradiol. Changes in flow caused by intravenous infusion of 2 microg/h of the hormone at constant heart rate and aortic blood pressure in the left renal and superior mesenteric arteries were assessed using electromagnetic flowmeters. In six pigs, infusion of 17beta-estradiol caused an increase in renal blood flow, which averaged 12.1% of the control values, without affecting mesenteric blood flow. In the same pigs, after hemodynamic variables had returned to the baseline values, blockade of beta2-adrenergic receptors with butoxamine caused an increase in aortic blood pressure and an increase in renal and mesenteric resistance. The subsequent infusion of 17beta-estradiol elicited increases in renal and mesenteric blood flow which respectively averaged 19.6% and 12.8%. Therefore, the present study in anesthetized pigs have shown that the vasodilator responses of the renal and mesenteric circulations to 17beta-estradiol were attenuated and even masked by a tonic beta2-adrenoceptor mediated vasodilation. This indicates that some vasodilator effects elicited by normally used replacement doses of the hormone may not be apparent.     

Ethacrynic acid induced release of prostaglandin E to increase renal blood flow

Ethacrynic acid administered to anesthetized dogs was found to increase the level of prostaglandin E as determined by radioimmunoassay in renal venous blood at the time when renal blood flow was increased by this agent. No change was found in the renal venous level of prostaglandin F. When ethacrynic acid was administered after treatment with indomethacin, which blocks the increase in renal blood flow induced by the natriuretic agent, no increase in the renal venous level of prostaglandin E was seen. Thus, the dilation of the renal vasculature would appear to be caused by a stimulation of synthesis and release of prostaglandin E by ethacrynic acid.     

Effects of the thromboxane receptor antagonist SK&F 88046 in the canine, monkey and human coronary vasculature

U-46619, a stable "functional" thromboxane/endoperoxide receptor agonist, produced potent contractile responses in isolated canine, rhesus monkey and human left circumflex coronary arteries (EC50 = 9.11 x 10(-9)M, 1.98 x 10(-8)M and 3.50 x 10(-9)M, respectively). Canine intrapulmonary veins were also contracted potently by U-46619 (EC50 = 1.22 x 10(-9)M). SK&F 88046, a thromboxane A2 (TxA2) end-organ receptor antagonist, blocked the vasoconstrictor effects of U-46619 in the canine circumflex artery (KB = 1.33 x 10(-8)M), canine intrapulmonary vein (KB = 1.46 x 10(-9)M), monkey circumflex artery (KB = 8.47 x 10(-8)M), and human circumflex artery (KB = 8.49 x 10(-7)M). SK&F 88046 was 10-60 times more potent in the canine and rhesus monkey coronary vasculature than in the human coronary preparations. Intracoronary administration of U-46619 to anesthetized, open chest dogs produced a dose-related decrease in left circumflex coronary artery blood flow which resulted in decreases in left ventricular developed pressure, left ventricular positive and negative dP/dt, ascending aortic blood flow, and an increase in left ventricular end-diastolic pressure. The decrease in coronary blood flow and the hemodynamic changes were either attenuated or completely inhibited by i.v. administration of SK&F 88046 (2.5 mg/kg + 0.05 mg/kg/min or 5.0 mg/kg + 0.1 mg/kg/min). SK&F 88046 was compared to two other TxA2 receptor antagonists in canine isolated intrapulmonary veins. SQ 29,548 was approximately 2-times more potent than SK&F 88046 as an antagonist of U-44619 mediated contractions (KB = 7.0 x 10(-10)M). In contrast, BM 13.177 was 150-fold less potent (KB = 2.19 x 10(-7)M) than SK&F 88046. Thus, the present study demonstrates species variability in response to TxA2 agonists and antagonists and reconfirms the relative importance of species selection in studying these agents.     

Upstream pressure for systemic to pulmonary flow from bronchial circulation in dogs

Systemic to pulmonary flow from bronchial circulation, important in perfusing potentially ischemic regions distal to pulmonary vascular obstructions, depends on driving pressure between an upstream site in intrathoracic systemic arterial network and pulmonary vascular bed. The reported increase of pulmonary infarctions in heart failure may be due to a reduction of this driving pressure. We measured upstream element for driving pressure for systemic to pulmonary flow from bronchial circulation by raising pulmonary venous pressure (Ppv) until the systemic to pulmonary flow from bronchial circulation ceased. We assumed that this was the same as upstream pressure when there was flow. Systemic to pulmonary flow from bronchial circulation was measured in left lower lobes (LLL) of 21 anesthetized open-chest dogs from volume of blood that overflowed from pump-perfused (90-110 ml/min) pulmonary vascular circuit of LLL and was corrected by any changes of LLL fluid volume (wt). Systemic to pulmonary flow from bronchial circulation upstream pressure was linearly related to systemic arterial pressure (slope = 0.24, R = 0.845). Increasing Ppv caused a progressive reduction of systemic to pulmonary flow from bronchial circulation, which stopped when Ppv was 44 +/- 6 cmH2O and pulmonary arterial pressure was 46 +/- 7 cmH2O. A further increase in Ppv reversed systemic to pulmonary flow from bronchial circulation with blood flowing back into the dog. When net systemic to pulmonary flow from bronchial circulation by the overflow and weight change technique was zero a small bidirectional flow (3.7 +/- 2.9 ml.min-1 X 100 g dry lobe wt-1) was detected by dispersion of tagged red blood cells that had been injected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blockade of the systemic and renal vascular actions of angiotensisn II with the 1-sar, 8-ala analogue in the rat.

To assess the characteristics of blockade induced by 1-Sar, 8-Ala angiotensin II (P113) in the rat, dose-response relationships were established for angiotensin II and blood pressure, cardiac output and renal blood flow (measured with microspheres) and calculated total peripheral resistance. P113 infused at 1.0 μg/kg/min reduced renal and systemic vascular responses to angiotensin II, but did not modify the pressor response because of compensatory increase in cardiac output. Ganglionic blockade (pentolinium tartrate 2.5 mg) uncovered a significant influence of P113 at 1.0 μg/kg/ min on pressor responses to angiotensin II. P113 at 10 μg/kg/min totally prevented the pressor and renal vascular response to 1.0 μg/kg/min of angiotensin II. P113 at 10 and 100 μg/kg/min did not influence renal blood flow, cardiac output or total peripheral resistance, and had only a transient, small influence on blood pressure. P113 did not modify the renal or systemic vascular response to norepinephrine. The failure of P113 to influence renal blood flow in the rat and the relative insensitivity of the renal vasculature to angiotensin II suggest that the vascular receptor for angiotensin II in the rat differs from that in other species including the dog, rabbit and man.     

Inhibition of platelet-activating factor induced renal hemodynamic and tubular dysfunctions with L-655,240, a new thromboxane-prostaglandin endoperoxide antagonist

The continuous infusion or bolus injection of the platelet-activating factor (PAF) is associated with profound hypotension, marked reductions of renal plasma flow, glomerular filtration, and urinary sodium excretion. All these effects are inhibited by blocking PAF receptors. To examine further the potential mediators of PAF on renal function, we utilized L-655,240 (6 mg/kg, intravenously), a thromboxane-prostaglandin endoperoxide antagonist, to study the systemic and renal response to PAF (0.8 micrograms/kg, intravenously) in the anesthetized dog, using clearance methodology. PAF decreased blood pressure from 115 +/- 7 to 54 +/- 4 mmHg (1 mmHg = 133.3 Pa), renal plasma flow from 105 +/- 6 to 74 +/- 56 mL/min, and glomerular filtration from 43 +/- 3 to 32 +/- 1 mL/min. PAF also reduced urine volume from 1.1 +/- 0.2 to 0.4 +/- 0.1 mL/min, and urinary sodium from 158 +/- 7 to 86 +/- 7 mu equiv./min. L-655,240 alone had no significant effect on blood pressure, renal plasma flow, and filtration rate, at any dose. However, the 6-mg/kg dose resulted in a slight elevation of diuresis, from 1.1 +/- 0.2 to 1.9 +/- 0.1 mL/min, and urinary sodium, from 134 +/- 13 to 212 +/- 19 mu equiv./min. All doses of L-655,240 blocked the effect of PAF on blood pressure. However, the two lower doses of this antagonist (1 and 3 mg/kg) failed to prevent the PAF-induced fall of renal plasma flow and filtration rate, and attenuated the effect on urinary sodium in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute renal function in chronically sympathectomized deoxycorticosterone acetate-treated miniature swine

We recently validated a swine model in which chronic treatment with 6-hydroxydopamine (6-OHDA) produced an effective sympathectomy. These sympathectomized swine demonstrated a significantly attenuated hypertensive response when treated with deoxycorticosterone acetate (DOCA). Because renal nerve activity is elevated and important in controlling renal function and blood pressure in the DOCA swine model, we wanted to study the effect of chronic sympathectomy on acute renal hemodynamics and tubular function. Kidney function was assessed in 14 DOCA-treated miniature swine, 8 of which were sympathectomized by chronic treatment with 6-OHDA, while 6 served as controls. Effective renal sympathectomy in this model has been previously confirmed by a significant reduction (97%) of norepinephrine in renal cortical tissue. When anesthetized, mean arterial pressure and renal blood flow were similar between the two groups. Glomerular filtration rate was lower by 43%, urine flow rate by 71%, sodium excretion by 66%, and potassium excretion by 48% in the 6-OHDA DOCA animals. All of these parameters were significantly different from the intact DOCA controls. These results indicate that anesthetized, chronically sympathectomized swine exhibit decreased renal excretory function. The changes in renal function may have been due to the development of a tubular or glomerular supersensitivity to circulating antinatriuretic factors, since the 6-OHDA group had a 28% greater pressor response to the alpha-agonist phenylephrine and a significantly greater fall in mean arterial pressure in response to alpha-blockade with prazosin when compared with the controls. These changes in renal function may also explain why the 6-OHDA animals demonstrated a slight increase in mean arterial pressure in response to DOCA. Because acute renal denervation in DOCA-treated swine produces a diuresis and natriuresis, this study affirms that there may be important functional differences in acutely versus chronically denervated kidneys for which the implications under normal physiologic conditions are unknown.     

Telemetered renal responses in dogs during detection of explosives.

The primary objectove of this work was to develop and test a method of measuring and characterizing renal hemodynamic responses in unrestrained dogs. Recordings of left kidney blood flow and abdominal aortic pressure were obtained from unrestrained dogs through the use of a two-channel implanted telemetry system during episodes of search and detection of simulated explosives. In each of a number of sequences, the dog was first given a start signal, and after locating the hidden device, was rewarded with food. Data were assessed at the start, find, and recovery segments. The dynamic flow and pressure, together with a hydraulic renal model, were used to derive the total preglomerular and postglomerular vascular resistances and the mean level of glomerular hydrostatic pressure. Data from three dogs obtained by telemetry and analyzed through the use of the model have shown that compared to the start of the test, the location of hidden explosives results in a decrease in both the level of mean aortic blood pressure and the preglomerular resistance; whereas, the reward results in an elevation of mean blood pressure and preglomerular resistance. The postglomerular resistance varied less than the preglomerular resistance, and mean flow did not vary significantly. This work has shown that the stimulation of a reward and the successful performance of a task lead to significant renal responses in dogs. It has further shown that telemetry, when employed with improved data analysis techniques, permits renal hemodynamics to be assessed in unrestrained animal subjects.     

Effects of endothelin on renal hemodynamics and excretory functions in anesthetized dogs

The effects of endothelin on renal hemodynamics and excretory functions were investigated in anesthetized dogs. Infusion of endothelin at a rate of 1 ng/kg.min resulted in a slight but significant decrease in renal blood flow and an increase in renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg.min significantly decreased cardiac output, glomerular filtration rate, urine volume, and urinary sodium and potassium excretion, whereas it increased systemic vascular resistance. Mean arterial pressure and heart rate showed a transient decrease and increase, respectively, at doses higher than 50 ng/kg.min. Plasma renin activity and plasma aldosterone concentrations were increased only at the dose of 100 ng/kg.min. These effects lasted for more than 60 min. These results suggest that endothelin may have an important role in the modulation of renal functions as well as in the modulation of systemic hemodynamics.     

Effects of catechol ring fluorination on cardiovascular and renal activities of fenoldopam enantiomers

SK&F 87516 is a potent DA₁ receptor agonist with demonstrated renal vasodilator activity. SK&F 87516 is the 6-fluoro analog of another DA₁ agonist/renal vasodilator agent, fenoldopam. SK&F 87516 is a racemic mixture of two enantiomers, SK&F(R)-87516 and SK&F(S)-87516, and like fenoldopam, the (R)-enantiomer is responsible for the biological activities of the racemate. SK&F(R)-87516 is diuretic in spontaneously hypertensive rats and in dogs, whereas its enantiomer, SK&F(S)-87516 is inactive. SK&F(R)-87516 increases glomerular filtration rate, an effect which may account, in part, for its diuretic activity. Unlike fenoldopam, SK&F(R)-87516 is not associated with acute hypotensive activity, tachycardia, or stimulation of the renin-angiotensin-aldosterone system. The activity differences between SK&F(R)-87516 and fenoldopam are not related to differences in DA₁ agonist potency. The activity differences may be due to the differing effects of fluorine and chlorine on the electron distribution in the catechol ring, resulting in an enhanced effect of SK&F(R)-87516 at α₂-adrenoceptors. © 1994 Wiley-Liss, Inc.     

Effects of calcitonin gene-related peptide on renal blood flow in the rat

The effects of alpha-rat calcitonin gene-related peptide (alpha-rCGRP) on systemic and renal hemodynamics and on renal electrolyte excretion were examined in normal anesthetized rats. In one group of rats (n = 7), infusions of alpha-rCGRP at doses of 10, 50, 100, and 500 ng/kg/min for 15 min each produced dose-related and significant decreases in mean arterial pressure from a control of 130 +/- 3 mm Hg to a maximal depressor response of 91 +/- 2 mm Hg. During the first three doses of alpha-rCGRP, renal blood flow progressively and significantly increased from a control of 5.0 +/- 0.3 ml/min to a peak level of 6.3 +/- 0.3 ml/min achieved during the 100 ng/kg/min infusion. With the highest infusion rate of 500 ng/kg/min, renal blood flow fell below the control level to 4.5 +/- 0.2 ml/min (P less than 0.05). The responses in renal blood flow and mean arterial pressure were associated with reductions in renal vascular resistance. After cessation of alpha-rCGRP infusions, arterial pressure, renal blood flow, and renal vascular resistance gradually returned toward the baseline values. In another group of rats (n = 9), infusion of alpha-rCGRP for 30 min at 100 ng/kg/min produced a significant reduction in urinary sodium excretion from 0.28 +/- 0.06 to 0.14 +/- 0.5 muEq/min (P less than 0.05). Urine flow and urinary potassium excretion also appeared to decrease, but the changes were not significantly different (P greater than 0.05) from their respective baselines. These results demonstrate that alpha-rCGRP is a potent and reversible hypotensive and renal vasodilatory agent in the anesthetized rat. The data also suggest that alpha-rCGRP may have significant effects on the excretory function of the kidney.     

Impaired blood flow autoregulation in nonfiltering kidneys: effects of theophylline administration

To investigate blood flow autoregulation in filtering and nonfiltering kidneys, renal blood flow was determined during graded reductions in renal perfusion pressure in seven anesthetized dogs containing both a filtering and nonfiltering kidney. In each dog, one kidney was made nonfiltering by the method of EH Blaine, JO Davis, and RT Witty (Circ Res 27:1081-1089, 1970). Renal perfusion pressure was decreased from 129 to 115, 99, and 83 mm Hg by stepwise constriction of the suprarenal aorta. In filtering kidneys, the maximum decrease in renal perfusion pressure reduced renal blood flow only 20.1% of control whereas renal blood flow of nonfiltering kidneys decreased by 41.0% of control. During aortic constriction, renal vascular resistance of nonfiltering kidneys remained unchanged or slightly increased. These hemodynamic changes were associated with significantly greater autoregulation indices in nonfiltering kidneys. In eight dogs with nonfiltering kidneys, competitive inhibition of adenosine with theophylline (9 mg/kg iv) restored autoregulation of renal blood flow as shown by significant decreases in renal vascular resistance. These data indicate that in the nonfiltering kidney model, autoregulation of renal blood flow is impaired. It is suggested that this impaired autoregulatory response may result from renal ischemia and the vasoconstrictor influence of elevated intrarenal adenosine concentration.     

Prostaglandin E2 induced changes in renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat

Prostaglandin E₂, when infused into the renal artery of the dog, is a vasodilator and increases both renal interstitial hydrostatic pressure and sodium excretion. Similar studies in the rat, however, have been inconclusive. The present study examined the effect of prostaglandin E₂ infusion into the renal interstitium, by means of a chronically implanted matrix, on renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat. Prostaglandin E₂ was continously infused directly into the kidney interstitium to minic endogenous prostaglandin E₂ production by renal cells. The maximum change in each of these parameters occured when 10⁻⁵ M PGE₂ was infused. Renal blood flow increased from 4.70±0.91 to 5.45±0.35 ml/min (p<0.05) while renal interstitial hydrostatic pressure decreased from 3.9±0.4 to 2.6±0.5 mmHg (p<0.05) and fractional excretion of sodium decreased from 1.02±0.20 to 0.61±0.12% (p<0.05. Thus, the present study demonstrates that renal interstitial infusion of prostaglandin E₂ increases total renal blood flow but decreases both renal interstitial hydrostatic pressure and urinary sodium excretion in the rat.