Prostaglandin System Research Articles

Circadian rhythm of prostaglandin system in rat stomach

Circadian rhythm of prostaglandin system in rat stomach

Dissociation of the prostaglandin and renin angiotensin systems during captopril therapy for chronic congestive heart failure secondary to coronary artery disease

Neurohumoral systems are activated as compensatory mechanisms in congestive heart failure (CHF). A close correlation has been reported between the renin angiotensin and prostaglandin systems in CHF. Furthermore, serum sodium concentration provided an excellent index of hormonal status. In this study, these relations were examined after acute and chronic blockade of renin angiotensin system with captopril. Eight patients with advanced CHF (New York Heart Association III or IV) were studied. Before captopril treatment, all hormone levels were elevated. Mean plasma renin activity was 24 ± 7 ng Al/ml/hour, angiotensin concentration was 221 ± 11 pg/ml and aldosterone concentration was 82 ±17 pg/ml. Plasma PGE 2 metabolite was 1,425 ± 321 pg/ml. A close correlation was observed between plasma angiotensin II and PGE 2 metabolite levels (r = 0.7); inverse correlations existed between serum sodium concentration and PGE 2 metabolite levels (r = −0.9) and with plasma renin activity (r = −0.6). Captopril therapy reduced the plasma angiotensin II level to 38 ± 6 pg/ml and aldosterone concentration to 15 ± 3 pg/ml, but did not affect plasma renin activity (31 ± 10 ng Al/ml/ hour) when measured in 1 week. Paradoxically, PGE 2-metabolite levels increased further (to 3,031 ± 346 pg/ml) despite blockade of the renin angiotensin system. Serum sodium concentration no longer correlated with hormone levels. These effects were sustained at 2 months of follow-up. Thus, captopril caused a dissociation between the renin angiotensin system and prostaglandin. The activation of prostaglandin is probably due to captopril's effect on prostaglandin biosynthesis and may contribute to captopril's sustained efficacy in CHF.

Renal haemodynamic actions of pressor doses of lysine vasopressin in the rat.

1. Dose-response effects of lysine vasopressin on renal haemodynamics were studied in conscious rats infused with 2.5% (w/v) dextrose solution at 5.8 ml/h. 2. Lysine vasopressin was maximally antidiuretic in the absence of a significant pressor effect at a dose of 2.5 pmol h-1 100 g body weight-1. Doses of vasopressin greater than this induced a dose-dependent increase in arterial blood pressure. 3. The clearance of p-aminohippurate (PAH) was not significantly changed by vasopressin, even at pressor doses. Rats pre-treated with indomethacin to inhibit prostaglandin synthesis showed a decrease in PAH clearance during the infusion of vasopressin at a dose of 30 pmol h-1 100 g body weight-1, and this suggests that the renal vasoconstrictor actions of vasopressin are attenuated by dilator prostaglandins. 4. Inulin clearance was unchanged by non-pressor doses of vasopressin but was decreased in a dose-dependent manner by pressor doses. A maximal effect was induced by a dose of 30 pmol h-1 100 g body weight-1 which decreased inulin clearance from 3.23 +/- 0.76 (mean +/- S.E. of mean) to 1.60 +/- 0.37 ml/min (P less than 0.02). A change in inulin clearance (from 3.42 +/- 0.46 to 2.17 +/- 0.33 ml/min, P less than 0.01) was also observed in rats pre-treated with indomethacin and infused with vasopressin at the same dose. The magnitude of the change was not significantly different from that observed in rats which were not treated with indomethacin. 5. Control rats infused with dextrose showed a slight but significant increase in sodium excretion during the course of the experiment. A similar natriuresis was observed in rats infused with non-pressor doses of vasopressin but was considerably enhanced in rats infused with pressor doses of the peptide. The antidiuresis induced by vasopressin remained maximal in rats infused with pressor doses. 6. Potassium and osmolal outputs were unchanged by non-pressor doses of vasopressin but significantly increased during administration of pressor doses. 7. It is concluded that pressor doses of lysine vasopressin do not alter total renal perfusion in conscious rats when the prostaglandin system is intact. Glomerular filtration is, however, decreased in a dose-dependent manner by these amounts but the mechanism is unclear.

The relation of angiotensin-converting enzyme to the pregnancy-induced hypertension-preeclampsia syndrome

Angiotensin-converting enzyme, the polypeptide that converts angiotensin I to angiotensin II, was measured in the serum of 114 pregnant women who had normal blood pressure, pregnancy-induced hypertension-preeclampsia, and chronic hypertension with or without pregnancy-induced hypertension. Angiotensin-converting enzyme levels were unrelated to weeks of gestation. The angiotensin-converting enzyme levels were similar in normotensive women (21 .l f 6.9 units/ml), women with chronic hypertension without pregnancy-induced hypertension (23.1 -t 2.7 units/ml), and patients with pregnancyinduced hypertension where magnesium sulfate (22.6 & 6.7 units/ml) had been administered prior to angiotensin-converting enzyme assay, but these values were significantly less than those in patients with pregnancy-induced hypertension with no magnesium sulfate (29.1 f 6.5 units/ml) therapy and in women with chronic hypertension with superimposed pregnancy-induced hypertension (30.7 -e 4.4 units/ml) (p < 0.005). Maternal venous and umbilical venous and arterial angiotensin-converting enzyme levels were as follows: The maternal venous level was less than the cord venous level and greater than the cord arterial value. Neither neonatal size nor twin gestation influenced the angiotensin-converting enzyme levels. Patients with diabetes mellitus had variable angiotensin-converting enzyme values regardless of the status of the blood pressure. The physiologic theories of blood pressure control in pregnant women are discussed in relation to the renin-angiotensin, bradykinin, and prostaglandin systems, (AM J OBSTET GYNECOL~ 986; 154:792-800.)

Indomethacin does not alter the circulating catecholamine response to asphyxia in the neonatal piglet.

The response of circulating catecholamines to asphyxia in unanesthetized, spontaneously breathing neonatal piglets was measured before and after treatment with indomethacin. Prior to treatment with indomethacin, baseline levels [geometric mean, pg/ml (95% confidence limits)] of D, E, and N were 162 (99-266), 174 (52-579), and 380 (286-506), respectively. Inhalation of 10% O2/9% CO2 for 20 min caused significant increases in arterial levels of all three catecholamines to 389 (230-659, 1514 (993-2306), and 3802 (2731-5293), respectively. Treatment with indomethacin (5 mg/kg, intravenous) did not significantly alter either baseline levels of the catecholamines or the levels after 20 min of the asphyxiating gas. In time control piglets, baseline levels and the response to asphyxia were similar before and after placebo. These results suggest that the circulating catecholamine response to asphyxia of the neonatal piglet is independent of the prostaglandin system.

Systemic haemodynamics, renal and platelet function during chronic propranolol administration in patients with compensated cirrhosis.

Chronic propranolol administration is followed by some haemodynamic alterations, which may impair renal function. It has also been suggested that it may reduce platelet production of proaggregatory thromboxane (TX) A2. We therefore evaluated cardiac index (CI), systemic vascular resistance (SVR), creatinine clearance, daily sodium excretion under controlled sodium intake, platelet aggregation and platelet TXA2 production during whole blood clotting in eight patients with cirrhosis, portal hypertension and no ascites, before and after 3 months of propranolol administration. Liver function was also assessed by evaluating the galactose elimination capacity (GEC) and galactose clearance (Cgal). The expected, significant reduction of CI and increase of SVR was observed. Creatinine clearance and sodium balance were unchanged throughout the study. Furthermore, the renal prostaglandin system, as reflected by urinary prostaglandin E2 and TXB2 excretion, was also unaffected by the drug. No modification of platelet aggregation, platelet TXA2 production during whole blood clotting, GEC and Cgal was observed. We conclude that chronic propranolol administration is followed by alterations of CI and SVR, but it does not impair renal function and platelet aggregation in patients with cirrhosis, portal hypertension and no ascites. The maintenance of renal function during beta-adrenergic blockade is not due to an increased renal production of vasodilating prostaglandins.

Participation of the Prostaglandin System in Furosemide-Induced Changes of Renal Function in Anesthetized Rats

The possible mediation of the endogenous prostaglandin and kallikrein-kinin systems of changes in renal function induced by furosemide was studied in anesthetized rats. Increasing doses of furosemide infusion (0.03, 0.1, and 0.3 mg/kg/min) caused dose-related diuresis, natriuresis, kaliuresis, and decreased renal blood flow and urinary osmolality without any significant changes in mean arterial blood pressure. Pretreatment with the prostaglandin synthetase inhibitor indomethacin resulted in marked reduction of the water and sodium excretion induced by furosemide. It also blunted renal vasoconstriction and renin release by furosemide, but the glomerular filtration rate was not affected. Pretreatment with aprotinin, a kallikrein inhibitor, failed to affect the renal response to furosemide. The results indicate that the renal prostaglandin system, but not the kallikrein-kinin system, participates in the effect of furosemide on renal functions mainly through electrolyte transport inhibition in the renal tubule.

The pathophysiological role of renal dopamine, kallikrein kinin and prostaglandin systems in essential hypertension.

In order to clarify the relationship and the pathophysiological role of renal dopamine, kallikrein-kinin and prostaglandin systems in essential hypertensives, the effects of dopamine on these systems and renal sodium handling were investigated. Basal levels of kallikrein, kinin and prostaglandin E2 in essential hypertensives were significantly lower than those in normotensives. Those of kallikrein and kinin were obviously more suppressed in the low renin group than in the normal renin group, but no significant difference in prostaglandin E2 was found in either subgroup. Urinary dopamine excretion was significantly lower in the low renin essential hypertensives, while no significant difference was found between normotensives and normal renin essential hypertensives. Kallikrein activity and prostaglandin E2 were significantly increased in essential hypertensives by dopamine infusion, and no significant difference was found in kallikrein-quantity and kinin between normotensives and essential hypertensives after the infusion. These increases of kallikrein and kinin were significantly higher in the low renin group than in normal renin group, but those of prostaglandin E2 were not. Urine volume, urinary sodium excretion and fractional excretions of sodium and inorganic phosphorus were all increased in both normotensives and essential hypertensives after dopamine infusion. The increases of these were significantly greater in essential hypertensives than in normotensives, and greater in the low renin group than the normal renin group. From these results, it was suggested that the dopamine, kallikrein-kinin and prostaglandin E2 system have a close relationship with each other, and the suppression of these systems may contribute to the pathophysiology of essential hypertension, especially in the low renin group.

Acute renal failure following traumatic injury or major operation.

Acute oliguria in the critically ill postoperative patient, or in the trauma victim after resuscitation, is a substantial clinical problem. The mortality associated with ARF in these settings remains unacceptably high. Evaluation of the oliguric patient must include thorough monitoring for, and correction of, prerenal and postrenal causes of oliguria. In this sense, diagnosis of ARF is one of exclusion. Differential diagnosis is facilitated by microscopic examination of urine and by biochemical analyses of blood and urine for calculating indices of tubular function (urinary-to-plasma ratios of blood urea nitrogen and creatinine, sodium excretion, and clearances of sodium, creatinine, solute, and water). The early detection of an intrarenal defect, as accomplished by using serial measurements of free water clearance, may allow interruption of the process and prevention of ARF. Preventive measures include optimization of hemodynamic status and the use of osmotic diuretic agents (mannitol) and loop diuretics (furosemide, ethacrynic acid, and bumetanide). Dopamine is useful for increasing both renal blood flow and urine flow and may be useful for preventing ARF, but this is not firmly established. Experimentally, other approaches such as modulating the renin-angiotensin system, prostaglandin system, and cellular calcium fluxes have been attempted, but the clinical applicability of these measures is not established. The best approach to ARF is preventing it by knowing which patients are at high risk, by studiously preventing renal insults, and by aggressively treating early indications of renal malfunction using established therapies.

Reduced excretion of vasodilator prostaglandins in preeclampsia.

The role of prostaglandin (PG) system in preeclampsia (pre-E) was investigated. Urinary excretion of PGE2,6-keto PGF1 alpha,2,3 dinor 6-keto PGF1 alpha, TxB2 and 2,3-dinor-TxB2 and kallikrein were determined in 10 normotensive pregnant women and 14 with pre-E. 6-keto PGF1 alpha and 2,3-dinor 6-keto PGF1 alpha (the main renal and extrarenal metabolites of vasodilator PGI2) and PGE2 excretion was lower in pre-E. TxB2 metabolites in urine were similar in the two groups of women. Our data are consistent with the hypothesis of an imbalance between vasodilator and vasoconstrictor PGs in pre-E.

P-50 - Participation of prostaglandin system in furosemide-induced renal motions in anesthetized rats

P-50 - Participation of prostaglandin system in furosemide-induced renal motions in anesthetized rats

Coronary vasodilation by nitrates is not mediated by the prostaglandin system: A quantitative cineangiographic study

The possible role of prostaglandins in mediating large coronary artery vasodilation by nitrates was investigated by quantitative magnification coronary angiography. The effects of aspirin (1 g systemically and 100 mg intracoronary) in preventing large coronary artery vasodilation induced by intracoronary isosorbide dinitrate was investigated in 16 patients. Of these, 5 received 0.3 mg (Group 1A) and 11 received 3 mg (Group 1B) intracoronary isosorbide dinitrate, before and 15 minutes after aspirin. Relative to control, 0.3 mg isosorbide dinitrate induced a 19 +/- 9% (mean +/- SD) (p less than 0.01) and 19.5 +/- 11% (p less than 0.01) increase in coronary diameter before and after aspirin, respectively (p = NS). Changes after 3 mg isosorbide were 23 +/- 12% (p less than 0.01) and 26.5 +/- 14% (p less than 0.01), respectively, before and after aspirin (p = NS). In 10 additional patients (Group 2), the effect of the same dose of aspirin on rest coronary artery tone was assessed: changes relative to control were 0.9 +/- 5.5% (p = NS) minutes after aspirin. The intracoronary administration of 3 mg isosorbide dinitrate produced a 24.7 +/- 11% increase in coronary diameter (p = NS versus pre- and postaspirin isosorbide in Group 1B). Urinary 6-ketoprostaglandin-F1 alpha values in urine samples collected in the 8 hours before and the 8 hours after the study in five patients in Group 1B and five patients of Group 2, revealed a 36 +/- 14% (mean +/- SD) reduction in excretion of prostacyclin (p less than 0.01). These data rule out a role for prostaglandins both in mediating dilation of large coronary arteries by nitrates and in affecting their vascular tone at rest.

The relation of angiotensin-converting enzyme to the pregnancy-induced hypertension-preeclampsia syndrome

Angiotensin-converting enzyme, the polypeptide that converts angiotensin I to angiotensin II, was measured in the serum of 114 pregnant women who had normal blood pressure, pregnancy-induced hypertension-preeclampsia, and chronic hypertension with or without pregnancy-induced hypertension. Angiotensin-converting enzyme levels were unrelated to weeks of gestation. The angiotensin-converting enzyme levels were similar in normotensive women (21.1 ± 6.9 units/ml), women with chronic hypertension without pregnancy-induced hypertension (23.1 ± 2.7 units/ml), and patients with pregnancy-induced hypertension where magnesium sulfate (22.6 ± 8.7 units/ml) had been administered prior to angiotensin-converting enzyme assay, but these values were significantly less than those in patients with pregnancy-induced hypertension with no magnesium sulfate (29.1 ± 6.5 units/ml) therapy and in women with chronic hypertension with superimposed pregnancy-induced hypertension (30.7 ± 4.4 units/ml) (p < 0.005). Maternal venous and umbilical venous and arterial angiotensin-converting enzyme levels were as follows: The maternal venous level was less than the cord venous level and greater than the cord arterial value. Neither neonatal size nor twin gestation influenced the angiotensin-converting enzyme levels. Patients with diabetes mellitus had variable angiotensin-converting enzyme values regardless of the status of the blood pressure. The physiologic theories of blood pressure control in pregnant women are discussed in relation to the renin-angiotensin, bradykinin, and prostaglandin systems.

Prostaglandins, prostacyclin, and thromboxane in cardiovascular diseases

AbstractProstaglandins appear to play an important role in or to be found therapeutically useful in various cardiovascular diseases, such as hypertension, arrhythmias, ventricular fibrillation, arterial thrombosis, myocardial ischemia, myocardial infarction, certain types of angina pectoris, atherosclerosis, circulatory shock, and peripheral arterial diseases, etc. Prostacyclin and prostaglandins E1, E2, and D2 are considered beneficial, while thromboxane A2 and prostaglandin F2α are considered harmful and their formations should be inhibited. Inhibition of the formation of the vasodepressor prostaglandins, such as prostacyclin and prostaglandin E2, in humans and animals leads to increase in arterial blood pressure and total peripheral resistance as well as to decrease the efficacy of most antihypertensive drugs, which suggests that these vasodepressor prostaglandins play an important role in hypertension. Most prostaglandins exert antiarrhythmic activity. Prostacyclin and thromboxane synthetase inhibitors are particularly effective in myocardial infarction/reperfusioninduced arrhythmias and ventricular fibrillation (sudden cardiac death) where the classical antiarrhythmic agents are not very effective. Prostacyclin and thromboxane synthetase inhibitors are effective in reducing myocardial infarct size, increasing coronary blood flow, and inhibiting arterial thrombosis. Atheroclerosis may result from decrease in prostacyclin formation in the blood vessel wall due to inhibition by the concentration of lipid peroxides in the blood. Prostacyclin stimulates cholesterol ester hydrolase, the enzyme that converts cholesterol ester to free cholesterol for mobilization out of the cells. PGE2 inhibits acyl CoA cholesterol‐O‐acyltransferase (ACAT), the enzyme that catalyzes the reesterification of free cholesterol. Therefore, prostacyclin, PGE2, and their stable analogs may be useful for the prevention and induction of regression of atherosclerosis. Prostacyclin, PGE1, and other stable prostaglandin analogs, such as iloprost and viprostol, have been reported to be beneficial for the treatment of peripheral arterial diseases. It is very likely that new drugs that affect the prostaglandin systems will be introduced for the prevention and treatment of various cardiovascular diseases in the very near future.

Effects of indomethacin on glomerular hemodynamics in experimental diabetes

The glomerular hemodynamics were studied in streptozotocin diabetic rats 3 months after the induction and in age-matched normal animals. Indomethacin infusion failed to cause changes in glomerular hemodynamics in normal rats but produced striking effects in the diabetic rats: The afferent arteriolar hydraulic resistance increased substantially while the efferent resistance rose moderately causing large reductions in single nephron blood flow and in the hydraulic pressure in the glomerular capillaries. Consequently, single nephron glomerular filtration rate (SNGFR) was reduced significantly below normal. The ultrafiltration coefficient of the glomerular membrane was significantly lower in the diabetic than in the normal animals (2.8 versus 5.0 nl min-1 mm Hg-1) and remained unchanged during indomethacin infusion. Our results suggest that the prostaglandin system compensates for the changes in the glomerular hemodynamics induced by diabetes by reducing the arteriolar resistances to increase the glomerular capillary pressure making it possible to maintain normal values of SNGFR and nephron blood flow.

PATHOPHYSIOLOGIC ASPECTS ‐ HEMODYNAMICS

Abstract The hemodynamic situation in congestive heart failure (CHF) is greatly influenced by compensatory mechanisms within the heart itself as well as released from die central nervous system and from the kidneys. These measures are intended to maintain the cardiac output at a level as beneficial as possible and to distribute the blood flow to regions with the largest metabolic demands. Thus the hemodynamic consequences of CHF are reflected in the central circulation as well as in the periphery.Within the heart the Frank‐Starling mechanism, adrenergic stimulation causing increase of heart rate and contractility, and during the chronic course also myocardial hypertrophy are operating. The central nervous and peripheral adaptive measures include increased sympathetic outflow bringing about an increased vasomotor tone with augmentation of pre‐ and afterload, and activation of the renin‐angiotensin‐aldosterone system, where angiotensin II further augments vasoconstriction directly and through central nervous stimulation. This vasoconstriction may be counteracted by humoral factors with vasodilatory properties, such as dopamine, bradykinin, acetylcholine and the metabolic products adenosine and lactic acid. The exact role of these and the possible importance of the antidiuretic hormone, arginine vasopressin, the prostaglandin system and the recently discovered atriopeptin remains to be established.As the compensatory mechanisms may maintain a fairly satisfactory hemodynamic situation at rest, investigations should be performed not only at rest but also during exercise to get an over‐all impression of the cardiac functional state It should be realized, however, that adaptive mechanisms cause the hemodynamics in chronic heart failure to differ from those in the acute phase in many respects. This is true particularly during physical exercise.The great importance of neurohumoral and endocrine factors in the compensatory regulation of the failing circulation warrants the definition of heart failure to be extended to “a failure of the heart to maintain cardiac output at a level which is adequate to meet the metabolic demands of the tissues, with preserved normal filling pressures and with undisturbed neurohumoral and endocrine equilibrium”.

ANTI-INFLAMMATORY ACTIVITY OF 6MFA, A COMPOUND OBTAINED FROM FUNGUS ASPERGILLUS OCHRACEUS

6MFA, an interferon-inducing substance obtained from fungus, Aspergillus ochraceus, has shown anti-inflammatory activity both in acute and chronic animal models of inflammation. It was found that 6MFA was equally effective in inhibiting both exudative as well as granulative phase of inflammation. The compound suppressed also cellular migration during inflammatory process and potentiated significantly the anti-inflammatory activity of indomethacin. The compound was devoid of analgesic or antipyretic activity. The probable mechanism of action of this compound is not fully understood. However, the possibility of triggering the induction of endogenous anti-inflammatory substance(s) along with interferon(s), or interaction of induced interferon(s) directly or indirectly with the prostaglandin system has been attributed.

Studies on Mechanisms of Antinephritic Action of SA-446, an Angiotensin I Converting Enzyme Inhibitor (1) A Comparison with Actions of Spironolactone, Kallidinogenase and Saralacin

The present study was made to clarify the mechanisms of the antinephritic action of SA-446, an angiotensin I converting enzyme inhibitor, on crescentic-type anti-GBM nephritis in rats as compared to the actions of spironolactone (an antialdosterone agent), kallidinogenase (a kallikrein agent) and saralasin (an angiotensin II antagonist). SA-446 (25 mg/kg/day, p.o.) had a tendency to reduce the urinary protein excretion and plasma urea nitrogen content. In addition, this drug remarkably inhibited not only glomerular histopathological changes (i.e., crescent formation, the adhesion of capillary walls to Bowman's capsule and fibrinoid necrosis) but also the elevation of blood pressure. Spironolactone (25 mg/kg/day, p.o.) and kallidinogenase (25 KU/day, i.m.) also showed beneficial effects on glomerular histopathological changes and hypertension, although both drugs were not as effective as SA-446. Flowever, saralasin (72 μg/day, s.c.) caused a marked aggravating action on this nephritis. This nephritic model showed a marked low activity of plasma renin all through the 40 day experimental period. In this model, the urinary aldosterone excretion was increased, in spite of the decrease in plasma renin activity. SA-446 and kallidinogenase significantly inhibited the decrease in plasma renin activity and the increase in urinary aldosterone excretion. Spironolactone inhibited only the increase in the aldosterone excretion. However, saralasin decreased the plasma renin activity under the control level and strongly increased the urinary aldosterone excretion (about 1.8 times the control level on the 20th day). These results suggest that the antinephritic effect of SA-446 may be related to the antihypertensive action and the increase in renal blood flow through activation of the kallikrein-kinin and prostaglandins systems.

Sodium and hypertension. Still a controversy in 1986.

Interpopulation studies support the hypothesis of a causal relationship between sodium consumption and arterial hypertension. However, although this association has been contradicted by intrapopulation studies, the correlation between sodium and hypertension appears to be genetically determined, as there are both sodium-sensitive and sodium-resistant individuals. Sodium is essential for the maintenance of extracellular and plasma volume equilibrium. It is controlled metabolically by the interaction of several biological systems such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the kallikrein-kinin and prostaglandin systems. Thus, sodium has a definite role in the mechanism involved in the pathophysiology of the predominantly volume-dependent forms of arterial hypertension. Recently, different structural substances with natriuretic effects have been identified. Natriuretic hormone is a non-peptide substance which inhibits the Na,K-ATPase in response to extracellular volume increase. This hormone acts on the renal tubular cells reducing sodium reabsorption, and at an arteriolar level elevating peripheral resistance by increasing smooth muscle tension. Mammalian atria contain various precursors of biologically active peptides, with potent natriuretic and diuretic effects. They are released in response to volume loading and atrial stretch. Although some data suggest an important role for these natriuretic substances in fluid volume and blood pressure control, their place in physiology and in abnormal clinical states should be more definitively clarified in the next few years.

The effect of suppression of prostaglandin synthesis on renal function in rats with intact and reduced renal mass

The present study was undertaken to assess the role of prostaglandin system in the compensatory response to reduced nephron population, respective to renal function and electrolyte excretion. Intact and 5 6 nephrectomized rats were divided in 4 groups: 1) rats pretreated with indomethacin, 2) rats pretreated with the vehicle of indomethacin, 3) rats pretreated with sulindac, and 4) rats pretreated with the vehicle of sulindac. In normal rats, indomethacin administration resulted in a mild decrease in creatinine clearance and a significant reduction of the urinary Na excretion. In the rats with reduced renal mass treated with indomethacin, the creatinine clearance did not differ from that in the control group. The 24 h urinary sodium excretion and the fractional excretion of sodium, however, were significantly lower in the indomethacin treated animals than in the control rats. No change in the creatinine clearance or in the sodium excretion was observed in all groups pretreated with sulindac. The urinary PGE 2 and thromboxane excretion was significantly lower in the indomethacin treated intact rats and the rats with reduced renal mass. Sulindac induced a slight decrease in urinary excretion of PGE 2 in intact rats. No significant change in urinary excretion of PGE 2 or thromboxane was seen after sulindac in the rats with reduced renal mass. The antinatriuretic effect of indomethacin was dissociated from changes in urine flow in all groups of animals, suggesting that the increase in Na reabsorption tool place in a water impermeable segment of nephron. These results suggest that the compensatory increase in urinary Na excretion per nephron in rats with reduced nephron population at least partly depends on an intact prostaglandin synthesis.