Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 2) Studies during moderate potassium depletion]

We have investigated the relative roles of angiotensin II on the renal function and urinary excretion of some prostanoids in healthy women submitted to different conditions of potassium balance. To this aim we have evaluated the effects of an acute inhibition of angiotensin converting enzyme by enalapril (E). The renal function was explored by clearance (cl.) method during induced hypotonic polyuria (oral water load followed by 5% dextrose solution infusion). During 60 min cl. period the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Each subject received paired studies, in absence and presence of E (10 mg administered per os 1 hour before the water load). Basal values of plasma renin activity (PRA) and urinary aldosterone (excreted during the 24 hours before the water load) were also determined by RIA method. This study protocol was applied in normal potassium balance (n = 6) and induced moderate potassium depletion (n = 6). This paper concerns the group in potassium depletion in both absence (D4) and presence of E (D4.E). Potassium depletion was induced by adaptation to a normal sodium (150 mmol/d) and low potassium (< or = 10 mmol/d) dietary intake combined to natriuretic treatment. The water and NaCl net losses were restored by 0.9% NaCl solution infusion. The cumulative potassium deficit achieved at the end of the depletive treatment was 214 +/- 54 mmol. This treatment induced significant decrease in basal plasma potassium concentration and increase in PRA without affecting urinary aldosterone and plasma sodium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 1) Studies during normal sodium and potassium balance]

We have investigated the effective role of angiotensin II on the renal function and urinary excretion of some prostanoids in healthy women submitted to different conditions of potassium balance. To this aim we have evaluated the effects of an acute inhibition of angiotensin converting enzyme by enalapril (E). The renal function was explored by clearance (cl.) method during induced hypotonic polyuria (oral water load followed by 5% dextrose solution infusion). During 60 min cl. period the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Each subject received paired studies, in absence and presence of E (10 mg administered per os 1 hour before the water load). Basal values of plasma renin activity (PRA) and urinary aldosterone (excreted during the 24 hours before the water load) were also determined by RIA method. This study protocol was applied in normal potassium balance (n = 6) and induced moderate potassium depletion (n = 6). This paper concerns the group in normal potassium balance in both absence (N3) and presence of E (N3.E). All subjects were submitted to normal dietary intake of sodium (150 mmol/d) and potassium (50 mmol/d). The basal values of PRA, urinary aldosterone and plasma electrolytes were in the normal range. The only significant effect produced by E was a reduction in mean arterial pressure, without significant changes in creatinine cl., urinary hydro-electrolyte excretions as well as urinary excretions of prostanoids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary prostanoid excretion in healthy women with different degrees of induced potassium depletion.

Plasma renin activity (PRA), urinary excretions of PGE2, 6-keto-PGF1 alpha (6KPGF), TXB2 and renal function were determined in healthy women both in normal potassium balance (N, n = 14) and in experimental potassium depletion (KD). KD was induced by natriuretic treatment--associated to replacement of net NaCl and water losses--in the presence of either normal (congruent to 50 mmol/d) or low (less than or equal to 10 mmol/d) dietary potassium intake. By using different depletive patterns, three groups with estimated cumulative potassium deficit (mean +/- SEM) of 124 +/- 38 (KD0, n = 8), 160 +/- 43 (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary prostanoid concentrations by the RIA method were estimated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by a low-dose infusion of lysine-8-vasopressin. 1. In KD0 group the potassium depletive treatment was inefficacious in significantly reducing either the plasma potassium concentration (PK) or the urinary potassium excretion (UKV). The reductions of PK and UKV as well as the enhancement of PRA became significant in KD1 and KD2 groups. 2. The urinary prostanoid excretions were not significantly changed in the KD0 and KD1 groups while in the KD2 group they were reduced, mainly concerning the urinary 6KPGF excretion. 3. Furthermore in the KD2 group, with larger potassium depletion, some of the typical hypokalemic renal dysfunctions appeared. The data suggest that a pathophysiologically critical degree of potassium depletion is associated with an inhibited renal prostanoid synthesis as well as an increased renin secretion.     

Selective inhibitory effects of experimental potassium depletion on urinary excretion of prostanoids and their possible functional significance

The urinary concentrations of prostaglandins(PG) E2, 6-keto-PGF1 alpha (6KPGF) and thromboxane (Tx) B2 were measured by RIA method during both hypotonic polyuria (oral water load) and subsequent antidiuresis (low-dose infusion of lysine-8-vasopressin). The study was performed on healthy women either in normal potassium balance (N, n = 14) or sustained potassium depletion (D3, n = 6). Potassium depletion (KD) was induced by low potassium dietary intake (less than or equal to 10 mmol/d) and natriuretic treatment over a period of 8 days; the net losses of NaCl and H2O were replaced; the cumulative potassium deficit was 198 +/- 22 mmol. Further studies were performed after indomethacin treatment in both experimental conditions. 1) As compared to normal potassium balance in KD group the urinary prostanoid excretions were reduced even in absence of significant differences in urinary flow rate. The urinary excretion of 6KPGF was more impaired than that of TxB2 in both polyuria and antidiuresis. 2) Indomethacin inhibited the urinary prostanoid excretions in normal potassium balance and KD groups. The urinary excretion of PGE2 was more impaired than that of both 6KPGF and TxB2.     

Low-dose desmopressin infusion: renal action in healthy women in moderate salt retention and depletion,and interactions with prostanoids

Studies were carried out to evaluate the influence of variations in sodium balance on the renal response to low-dose infusion of 1-desamino-8- D -arginine vasopressin (dDAVP), and the functional interaction between dDAVP and renal prostanoids. The studies were performed on healthy women in conditions of extracellular fluid volume expansion (SR group, n =9) and depletion (SD2 group, n=6), respectively. The study protocol included hypotonic polyuria (induced by oral water load) and subsequent antidiuresis (induced by low-dose infusion of dDAVP). Three 60-min clearance (cl.) periods were performed during polyuria (cl. P), early (cl. A1) and late (cl. A2) antidiuresis. The urinary concentrations of prostaglandin (PG) E(2) and the stable metabolites of PGI(2) and thromboxane (Tx) A(2), 6-keto-PGF(1alpha) (6KPGF) and TxB(2), were estimated. Paired renal functional explorations were performed in salt retention and salt depletion both in absence and presence of indomethacin (SR.I and SD2.I groups). In both paired and unpaired studies, the early and late effects of dDAVP on the functional excretory variables and the excretion of prostanoids were assessed as percentage variations, (A1-P)% P and (A2-A1)% A1. (I) dDAVP in salt retention and depletion. During early infusion dDAVP produced in both conditions a significant reduction in urinary flow rate, creatinine cl., absolute and fractional excretions of sodium, chloride and potassium; during late infusion dDAVP was effective in inducing a further significant reduction in urinary flow rate. In salt retention compared to depletion the early reductions in sodium and chloride (absolute and fractional) excretions were significantly lower. (II) Indomethacin pretreatment. During early infusion the dDAVP-induced reductions in the urinary flow rate and 6KPGF excretion were enhanced in both conditions. In salt depletion the dDAVP effects in reduction of creatinine cl. and urinary electrolyte excretions were also enhanced. During late infusion the antidiuretic effect of dDAVP was suppressed in salt retention, while in salt depletion creatinine cl., the urinary excretions of electrolytes and both 6KPGF and TxB(2) showed increases significantly different from the dDAVP effects in the absence of indomethacin. In conclusion, (a) the salt-retaining effect of dDAVP was less effective in salt retention compared to depletion. (b) Indomethacin pretreatment affected the renal action of dDAVP in a time-dependent pattern. The early effects in both conditions were consistent with an inhibited synthesis of modulator PGs. On the contrary, the late effects were consistent with the occurrence, at least in salt depletion, of an escape from dDAVP renal action. This escape phenomenon probably depended on a partial regression of the pharmacological inhibition of the modulating PGs.     

Further research on the role of prostanoids in controlling renal function in humans in normal potassium balance and acute experimental potassium depletion. I: Studies of normal potassium balance. Effects of indomethacin

The renal function was studied by clearance (cl.) method during hypotonic polyuria (oral water load followed by 5% dextrose solution infusion) and successive relative antidiuresis induced by lysine-8-vasopressin (LVP) administration (5 microU in bolo followed by continuous infusion at a rate of 0.04 microU/min). Four 15 min and two 60 min clearance (cl.) periods were performed during hypotonic polyuria and antidiuresis, respectively. Glomerular filtration rate was estimated by creatinine cl.; the osmotic cl. (Cosm, CH2O), the absolute and fractional excretions of water, sodium, potassium and chloride were determined by usual methods. The urinary PGE2, 6-keto-PGF1 alpha and TxB2 concentrations were determined by RIA method. Fourteen healthy women submitted to a normal sodium and potassium daily intake were studied; in 6 of them paired studies in absence and in presence of indomethacin (100 mg, i.m.), respectively, were performed. LVP induced a significant reduction of creatinine cl., urinary flow rate and of prostanoid excretion. In hypotonic polyuria, indomethacin significantly reduced the creatinine cl. and the diuretic response to the water load; moreover the urinary PGE2 and 6-keto-PGF1 alpha excretions were significantly lower (85.6 +/- 1.9% and 37.7 +/- 3.2%) while the reduction of urinary TxB2 excretion was not significant (34.4 +/- 13%). Indomethacin did not affect significantly the LVP renal effects in normal potassium balance.     

Renal function and urinary prostanoid excretions in salt-depleted women: comparative effects of enalapril and indomethacin treatments.

The acute effects on urinary prostanoid excretion and on renal function induced by pharmacological inhibition of either the angiotensin-converting enzyme or of the cyclooxygenase system, respectively, have been studied in healthy salt-depleted women. Two experimental groups were studied during salt depletion, SD1 (n=8) and SD2 (n=6). Salt depletion was obtained by combining a low sodium chloride dietary intake (< or =60 mmol per day) with natriuretic and potassium sparing treatment. Paired studies were performed in the absence and in the presence of enalapril (SD1 group) or indomethacin (SD2 group). In both paired studies renal function was estimated by the clearance (cl.) method and the urinary concentrations of PGE2, 6-keto-PGF1alpha and TXB2 were estimated by RIA during sustained hypotonic polyuria (induced by oral water load). Enalapril did not influence urinary excretion of prostanoids. Its main significant effects were: (a) a reduction in mean arterial pressure (MAP); (b) an increase in free-water cl. (C(H2O)) and a reduction in osmolar cl. (Cosm); (c) a reduction in the absolute and fractional urinary excretions of sodium and chloride; and (d) a reduction in both the plasma concentration and urinary excretion of potassium. The urinary flow rate and the creatinine cl. were not significantly affected. Indomethacin reduced urinary excretion of prostanoids and in addition it produced the following significant effects: (a) a reduction in urinary flow rate, C(H2O) and Cosm values, and in absolute and fractional urinary excretions of sodium and chloride; and (b) an increase in plasma potassium concentration. MAP, creatinine cl. and urinary potassium excretion were not significantly affected. With regard to the main parameters, both enalapril and indomethacin exerted similar effects on urinary sodium and chloride excretion but opposite effects on C(H2O) and plasma potassium concentration. In conclusion, after enalapril in a salt-depleted state, the functional expression of acute angiotensin II deprivation was partially masked by the activation of a homeostatic system responsible both for improvement in renal salt conservation and for facilitated cellular potassium uptake. After indomethacin in the same setting, the results were consistent with a differential role of prostanoids in modulating or mediating the activities of neuro-hormonal agonists.     

Low-dose dopamine as an activator of renal catecholamine receptors of different classes. I. Studies in water-salt depletion

The renal function in healthy man with salt and water depletion induced by natriuretic treatment was explored during steady hypotonic polyuria. Four 15 min clearance (cl.) periods, before, during and after dopamine (DA) infusion in a subpressor dose were performed. The 12 examined subjects showed different renal hemodynamic responses in the early stage of DA infusion, i.e. hyperemic (4 subjects, subgroup A) or ischemic (8 subjects, subgroup B). A decrease in urinary sodium excretion and increase in tubular sodium reabsorption, in particular at the diluting segment level, were induced by DA in both subgroups, at least in the late stage of infusion. During the control cl. period in subgroup A as compared with B the renal plasma flow was lower and the tubular sodium reabsorption higher, suggesting a relatively higher level of renal adrenergic activity.     

Renal function in experimental potassium depletion. I. Effects of lysine-8-vasopressin in hypotonic polyuria

Renal function has been studied by the clearance (cl.) method during hypotonic polyuria--four 15-min cl. periods--and successive antidiuresis--two 60-min cl. periods (A1, A2)--induced by lysine-8-vasopressin (LVP), 5 mU in bolus followed by infusion at a rate of 0.04 mU/min. The endogenous creatinine cl. (Cc) and the osmotic cls. (Cosm, CH2O) were determined by the usual methods as well as the absolute and fractional urinary excretions of water, sodium, chloride and potassium. The urinary concentrations of PGE2, 6-keto-PGF1 alpha and TxB2 were determined by the RIA method. This study protocol has been applied to 28 healthy women either in normal potassium balance (N, n = 14) or after potassium depletion (KD) induced by low potassium dietary intake (less than or equal to 10 meq/d) plus natriuretic treatment according to two different time patterns: two KD groups were obtained with potassium cumulative deficit of 160 +/- 43 (D2, n = 8) and 198 +/- 22 meq (D3, n = 6). The early % effects of LVP, i.e. (A1-P)% of P (mean polyuria), were significantly different only in D3 as compared to N. Precisely, the LVP-effect to reduce Cc was blunted; moreover a LVP-effect to reduce renal sodium and chloride fractional excretions and a tendentiously enhanced LVP-effect to reduce water fractional excretion were observed. These tubular effects are likely related to the inhibited renal synthesis of prostanoids in the D3 group.     

Renal function in experimental potassium depletion. II. Indomethacin and effects of lysine-8-vasopressin in hypotonic polyuria

Renal function has been studied by the clearance (cl.) method during hypotonic polyuria--four 15-min cl. periods--and successive antidiuresis--two 60-min cl. periods (A1, A2)--induced by lysine-8-vasopressin (LVP), 5 mU in bolus followed by infusion at a rate of 0.04 mU/min. The endogenous creatinine cl. (Cc) and the osmotic cls. (Cosm, CH2O) were determined by the usual methods as well as the absolute and fractional urinary excretions of water, sodium, chloride and potassium. The urinary concentrations of PGE2, 6-keto-PGF1 alpha and TxB2 were determined by the RIA method. This study protocol has been applied to 20 healthy women submitted to paired functional explorations in both the absence and presence of indomethacin (100 mg i.m.); the drug effects have been evaluated in both normal potassium balance (N2, n = 6) and in two groups of potassium depletion (KD) with potassium cumulative deficit of 160 +/- 43 (D2, n = 8) and 198 +/- 22 meq (D3, n = 6), respectively. As regards the early % effects of LVP, i.e. (A1-P)% of P (mean polyuria), the inhibition of prostanoid synthesis with indomethacin produced significant changes: 1) an enhanced reduction in renal chloride excretion in all experimental groups; 2) a reduction in renal sodium and chloride fractional excretions in both KD groups; 3) an enhanced antidiuretic effect in D3 only, i.e. in the experimental condition with inhibition of prostanoid renal synthesis present during the control study.     

Changes in urine volume and urinary electrolyte excretion after intracerebroventricular injection of arecoline and hemicholinium-3

Activation of cholinergic neurons in specific brain regions evokes a hypernatriuretic response, which appears to be atropine-sensitive and, perhaps, independent from the renal innervation. However the role of cholinergic neurons in central control of renal function is not well understood. The purpose of this study was to further investigate whether brain acetylcholine stores are able to influence kaliuresis and natriuresis in conscious rats. Therefore, the renal response to cholinergic drugs was examined in Wistar rats which underwent to a 0.15 M NaCl solution (saline) load administered by gavage. Central injection of arecoline, a muscarinic agonist, produced a dose-dependent reduction in water diuresis and a highly significant increase in sodium excretion within two hours from the oral saline load. An intracerebroventricular (ICV) injection of methylatropine completely blocked both the antidiuretic and the natriuretic response induced by arecoline. Hemicholinium-3 (HC), centrally administered at a dose (34.8 nmol) known to be capable of inducing a maximal depletion of brain acetylcholine, elicited a time-dependent antidiuretic effect accompanied by a highly significant reduction in potassium and sodium urinary excretion. Therefore, we suggest that brain cholinergic neurons are involved in the regulation of the electrolyte balance.     

Gastrointestinal osmoreceptors and renal sodium excretion in humans

The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered by a nasogastric tube as isotonic or hypertonic saline (850 mM). In additional experiments, salt loading was replaced by oral water loading (3.5% of total body water). Plasma sodium concentration increased after hypertonic saline (+3.1 +/- 0.7 mM), decreased after water loading (-3.8 +/- 0.8 mM), and remained unchanged after isotonic saline. Oncotic pressure decreased by 9.4 +/- 1.2, 3.7 +/- 1.2, and 10.7 +/- 1.3%, respectively. Isotonic saline induced an increase in renal sodium excretion (104 +/- 15 to 406 +/- 39 micromol/min) that was larger than seen with hypertonic saline (85 +/- 15 to 325 +/- 39 micromol/min) and water loading (88 +/- 11 to 304 +/- 28 micromol/min). Plasma ANG II decreased to 22 +/- 6, 35 +/- 6, and 47 +/- 5% of baseline after isotonic saline, hypertonic saline, and water loading, respectively. Plasma atrial natriuretic peptide (ANP) concentrations and urinary excretion rates of endothelin-1 were unchanged. In conclusion, stimulation of osmoreceptors by intragastric infusion of hypertonic saline is not an important natriuretic stimulus in sodium-replete subjects. The natriuresis after intragastric salt loading was independent of ANP but can be explained by inhibition of the renin-angiotensin system.     

Further research on the role of prostanoids in controlling renal function in humans in normal potassium balance and acute experimental potassium depletion. III: Effects of indomethacin in potassium depletion

The renal function was evaluated by clearance (cl.) method during hypotonic polyuria and successive relative antidiuresis induced by lysine-8-vasopressin administration. Four 15 min and two 60 min cl. periods were performed in hypotonic polyuria and antidiuresis, respectively. Glomerular filtration rate was estimated by creatinine cl., the osmotic cl. (Cosm' CH2O), the absolute and fractional excretions of water, sodium, potassium and chloride were determined by usual methods. The urinary PGE2, 6-keto-PGF1 alpha and TxB2 excretions were determined by RIA method. The study protocol was applied on 14 healthy women in acute potassium depletion, treated with indomethacin (100 mg i.m. at the end of the oral water load). In Group D3 (n = 6) in the presence of a greater potassium cumulative deficit (198.4 +/- 22.2 meq), in hypotonic polyuria, indomethacin induces significant effects as an increase of fractional hydro-electrolytic reabsorptions and as a decrease of urinary prostanoid excretion. The indomethacin tubular action in potassium depletion differs significantly from that observed in normal potassium balance.     

Relation between acute changes in diuresis and renal prostaglandins. I: Induced hypotonic polyuria

We have evaluated the effects of indomethacin (I) and of a rich in linoleic acid phosphatidylcholine (E) on the renal function and on the PGE urinary excretion during steady hypotonic polyuria. 5 normal subjects have been studied in the absence of treatment (TA) and after treatment with I, E, E + I. The renal function has been estimated by clearance (cl.) method during hypotonic polyuria induced by oral water loading and i.v. infusion of 5% dextrose solution. The glomerular filtration rate has been estimated by cl. of endogenous creatinine; moreover have been measured the osmotic clearances (Cosm, CH2O), the sodium and potassium clearances (CNa, CK), the mean arterial pressure (PA) and the urinary prostaglandins of E series (PGE) by RIA method. In I condition is observed: a) a trend to a glomerular filtration rate decrement; b) a significant decline of the urinary flow rate, CH2O, UPGV and a significant increment of the urinary osmolarity; c) a trend to an increment of potassium and a decrement of sodium urinary excretions; d) a significant increase of PA. It is possible that the contrary effects observed during the hypotonic polyuria in E condition depend on the stimulating effects of this material on the PG intrarenal synthesis.     

The effect of intravenous infusion of hyperosmotic sodium and potassium chloride solutions on cephalic blood flow in conscious sheep.

The rate of flow of plasma and blood through the head of conscious sheep was measured before, during and after the intravenous infusion of 1 mol. 1(-1) NaCl and 1 mol. 1(-1) KCl at 0-8--1-0 ml. min-1 for 2 hours. The plasma flow was estimated by indicator-dilution technique using sodium para-aminohippurate which was shown to be a satisfactory indicator substance. Short periods of rumination were found to cause marked increases in cephalic blood flow. The infusion of hyperosmotic sodium chloride caused no consistent changes in the rates of cephalic plasma flow and blood flow. During potassium infusion plasma and blood flows increased as the plasma potassium concentration increased up to approximately 6 mmol.1(-1). Further increases in plasma potassium concentration were associated with a progressive return of these flow rates to or below the pre-infusion levels. This pattern of change in the rate of plasma flow through the head of the sheep was very similar to that previously reported for renal plasma flow during hyperkalaemia in conscious sheep. At its maximum the cephalic plasma flow was 1-163+/-0-029 (S.E. of mean) times the pre-infusion flow rate. Cephalic blood flow tended to reach maximum rates at slightly higher plasma potassium concentrations and thereafter, to fall more slowly than the plasma flow due to concomitant increases in haematocrit. Maximum cephalic blood flow was 1-176+/-0-032 times the pre-infusion flow rate. The lowest rates of cephalic plasma and blood flow occurred during the first 30 minutes following cessation of potassium infusion.     

Effect on maternal and fetal renal function and plasma renin activity of a high salt intake by the ewe

The effect on renal function of replacing maternal drinking water with a solution containing 0.17 M NaCl was studied in 9 ewes and their chronically catheterised fetuses over a period of 9 days. Maternal sodium intake increased from control values of 2.19 +/- 0.09 mmol/h to 44.3 +/- 7.4 (P less than 0.001) and 46.3 +/- 6.5 mmol/h (P less than 0.001) on the 3rd and 6th days of salt ingestion. Maternal plasma sodium levels were not affected, but the urinary sodium/potassium ratio increased from 0.15 +/- 0.07 to 2.26 +/- 0.34 (P less than 0.001) after 6 days and plasma renin activity fell from 2.87 +/- 0.76 to 1.00 +/- 0.25 ng/ml per h (P less than 0.05). The changes in maternal sodium intake had no effect on fetal plasma sodium levels nor on fetal plasma renin activity. Sodium excretion and fetal urinary sodium/potassium ratio did not change. However, 3 days after the ewes returned to drinking water fetal plasma renin activity was significantly higher than it was prior to maternal ingestion of 0.17 M NaCl. Fetal plasma renin activity was inversely related to fetal plasma sodium levels (P less than 0.01). The results show that changes in maternal sodium intake had no long term effect on fetal plasma sodium levels nor on fetal renal sodium excretion. The fall in maternal plasma renin activity in the absence of any change in the fetal renin activity, indicates that the fetal renin angiotensin system is controlled by factors other than those influencing the maternal renin angiotensin system. Since fetal urinary sodium/potassium ratios remained unchanged it would suggest that fetal sodium excretion is not influenced by maternal levels of aldosterone.     

Water and sodium intake of wild and New Zealand Rabbits following angiotensin

Two rabbit strains, New Zealand (laboratory) rabbits and Australian wild rabbits, both members of the Oryctolagus cuniculus genus were studied. New Zealand rabbits under control conditions consumed 2-5 times more water and 8-30 times more 0.5 M NaCl/kg body weight than wild rabbits. Single injections of angiotensin II or III administered ICV did not induce water drinking in either strain. Acute ICV infusion of angiotensin II also did not influence water intake, but after several days of administration, induced increased sodium intake. Intravenous infusion of graded doses of angiotensin II induced diuresis only at the higher doses in both strains. In New Zealand rabbits, this was accompanied by a commensurate and concurrent increase in water intake. Intravenous infusion of angiotensin II also induced urinary sodium loss that was either accompanied or followed by increased sodium intake. The development of salt appetite in both strains was preceded by sodium loss.     

Low-dose dopamine as an activator of renal catecholamine receptors of different classes. II. Studies in water-saline depletion and associated adrenergic blockade

The renal function in healthy man with salt and water depletion (natriuretic pretreatment) associated with adrenergic blocking agents administration was explored during steady hypotonic polyuria. Four 15 min clearance (cl.) periods, before, during and after dopamine (DA) infusion in a subpressor dose, were performed. The 9 subjects treated with prazosin showed different renal hemodynamic responses in the early stage of DA infusion i.e. hyperemic (6 subjects, subgroup A) or ischemic (3 subjects, subgroup B). The whole group of 6 subjects treated with propranolol showed an hyperemic response DA infusion. A natriuretic effect and a trend towards tubular sodium reabsorption inhibition, in particular at the diluting segment level, were associated with the DA vasodilatory responses. The ischemic responses to DA occurred in the presence of incomplete alpha-adrenergic receptors blockade; nevertheless in the same circumstances DA failed to increase the diluting segment sodium reabsorption.     

Volume-induced natriuresis in healthy women: renal metabolism of prostacyclin and thromboxane, and physiological role of prostanoids

In healthy women submitted to a short-term expansion in extracellular fluid volume we have evaluated the urinary excretory profile of the stable metabolites of prostaglandin(PG) I2 and thromboxane(TX) A2, 6-keto-PGF1 alpha(6KPGF) and TXB2 respectively, and assessed the physiological role played by the prostanoids in this experimental condition. Salt retention (SR group, n=9) was induced by repeated i.v. infusion of saline solution (0.9% NaCl). At the end of the treatment the body weight had increased by 0.7+/-0.2 kg (mean+/-SEM) (P<0.05). Renal functional exploration [clearance (cl.) method] was performed during hypotonic polyuria (induced by oral water load) and subsequent moderate antidiuresis (induced by low-dose infusion of an antidiuretic hormone analogue). Urinary 6KPGF and TXB2 concentrations were estimated by RIA method during polyuria (P cl. period), early and late antidiuresis (A1 and A2 cl. periods). Paired functional explorations were performed in absence (control study) and presence of indomethacin. Basal values of plasma sodium and potassium concentrations, plasma renin activity (PRA) and urinary aldosterone excretion were determined just before the control study. The results in salt retention were compared to those previously obtained in healthy women submitted to a moderate salt depletion (SD2 group, n=6), in absence and presence of the drug. Women in salt retention received 100 mg i.m. of the drug, whereas salt-depleted women received only a halved dose as in previous studies in salt depletion the full dose produced prolonged anuria. (I) Salt retention vs salt depletion. The basal values of PRA and urinary aldosterone excretion were significantly lower. During polyuria, urinary excretion of 6KPGF, 6KPGF/TXB2 ratio, urinary flow rate, creatinine cl. and absolute and fractional excretions of sodium and chloride were significantly higher. In salt retention during polyuria, significant positive correlations were found between 6KPGF excretion and functional excretory parameters. (II) Indomethacin in salt retention. The following effects were significant: (a) a reduction in prostanoid excretions in P and A1 cl. periods only; (b) during polyuria, an increase in arterial pressure, a reduction in urinary flow rate and creatinine cl. (saluresis showed not significant reduction). During polyuria significant positive correlations occurred between the absolute effects of indomethacin on 6KPGF excretion and those on functional excretory parameters. (III) Comparative effects of indomethacin in salt retention and salt depletion. Despite the double dosage of the drug, the significant reductions in urinary metabolite excretions were not significantly different during P cl. period and significantly lower in A1 cl. period compared to the corresponding significant reductions in salt depletion. During polyuria, the significant increase in arterial pressure was significantly different from the not significant effect in salt depletion; the not significant effect on saluresis was significantly different from the significant reduction in salt depletion. The results suggest the following conclusions: (1) The present model showed the functional pattern of the volume-natriuresis; (2) In salt retention, in contrast with salt depletion, indomethacin induced an increase in arterial pressure consistent with the inhibition of a PG-dependent vasodilator mechanism active at the systemic level; (3) In salt retention, in contrast with salt depletion, indomethacin failed to induce a significant reduction in saluresis. This failure can be attributed to the drug's blunted effectiveness in inhibiting the renal synthesis of saluretic PGs, and probably to the interference of the concurrent increase in arterial pressure in the renal treatment of sodium and chloride.     

Control of renal and extrarenal salt and water excretion by plasma angiotensin II in the kelp gull (Larus dominicanus)

Summary The osmoregulatory effects of intravenously (i.v.) administered angiotensin II (AII) at dose rates of 5, 15 and 45 ng · kg^–1 · min^–1 were examined in kelp gulls utilizing salt glands and/or kidneys as excretory organs.In birds given i.v. infusion of 1200 mOsmolal NaCl at 0.3 ml · min^–1 and utilizing only the salt glands to excrete the load, infusion of AII for 30 min consistently inhibited salt gland function in a dose-dependent manner.In birds given i.v. infusion of 500 mOsmolal NaCl at 0.72 ml · min^–1 and utilizing both salt glands and kidneys to excrete the load, each dose of AII given for 2 h inhibited salt gland function but stimulated the kidney, so that the overall outputs of salt and water were enhanced and showed significant (2P<0.01) positive correlations with plasma AII.In birds given i.v. infusion of 200 mOsmolal glucose at 0.5 ml · min^–1 and utilizing only the kidneys to excrete the load, low doses of AII (5 and 15 ng · kg^–1 · min^–1) caused renal salt and water retention, whereas a high dose (45 ng · kg^–1 · min^–1) stimulated salt and water output.The actions of plasma AII in kelp gulls support the concept that this hormone plays a vital role in avian osmoregulation, having effects on both salt gland and kidney function. Elevation of plasma AII consistently inhibits actively secreting salt glands, but its effects upon renal excretion depend primarily on the osmotic status as well as on the plasma AII concentration. In conditions of salt and volume loading doses of AII stimulate sodium and water excretion. With salt and volume depletion, the action of AII is bi-phasic with low doses promoting renal sodium and water retention but high circulating levels causing natriuresis and diuresis.