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Biomedical subjects

P Lenzi

Publications and source records attributed to P Lenzi.

At least 73 records · Page 4Linked to original sources

Effects of experimental potassium depletion on renal function and urinary prostanoid excretion in normal women during moderate anti-diuresis.

The hypothesis that potassium depletion (KD) might play a role in stimulating the renal synthesis of prostanoids, and that these materials can contribute to hypokalaemic renal dysfunction, has been tested. Healthy women were studied either in normal potassium balance (N,n = 14), or in experimental KD. KD was induced by low dietary potassium intake (less than or equal to 10 mmol day-1) and natriuretic treatment, associated with replacement of net NaCl and water loss. By using different depletive patterns, two groups with estimated cumulative potassium deficits of 160 +/- 43 mmol (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary PGE2, 6-keto-PGF1 alpha, TxB2 concentrations by the RIA method were measured during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by the infusion of low-dose lysine-8-vasopressin (LVP). Compared to the N group, only in the KD2 group do glomerular and tubular dysfunctions typical of hypokalaemia and reduced prostanoid excretions (significant for 6-keto-PGF1 alpha and TxB2 but not for PGE2) appear during polyuria besides the significant reductions of plasma potassium concentration, urinary potassium excretion and the significant increase in plasma renin activity. During LVP infusion the urinary prostanoid excretions were all significantly lower in absence of significant differences in urinary flow rate. Concerning its renal effects, LVP lost its ability to reduce the creatinine cl., while expressing a trend towards reduction in fractional chloride excretion. Indomethacin pretreatment restored the LVP effect on creatinine cl. and increased the antichloruretic LVP effect (although not significantly). To the extent that urinary prostanoid excretions reflect their intrarenal synthesis, our data demonstrate that KD inhibits this biosynthesis. A depressed production of prostanoids endowed with vasodilating and chloruretic activity probably played a role in attenuating the renal vascular hyporeactivity and the urinary chloride dispersion induced by KD.

Adult↗

Loss of integrative control of peripheral circulation during desynchronized sleep.

Regional blood flow (BF) changes during sleep were measured in rabbits at low, neutral, and high ambient temperatures (Ta) with radioactive microspheres. At both low and high Ta, peripheral vasomotor changes at the onset of desynchronized sleep (DS) were incompatible with thermoregulatory homeostasis. At low Ta, BF decreased in muscle (with the disappearance of shivering), whereas it increased in the arteriovenous anastomoses (AVA) and in the splanchnic bed. At high Ta, BF decreased in muscle (with the disappearance of panting) and in the AVA, whereas it increased in the splanchnic bed. An impaired central nervous regulation underlies the disruption of peripheral circulation patterns in this sleep stage. The lack of adaptive vasomotor adjustments in DS, which has little consequence in normal conditions, may become relevant in cardiovascular pathophysiology when BF redistribution through increased neurogenic vasomotor activity becomes a major compensating mechanism.

Animals↗

Regional splanchnic blood flow during sleep in the rabbit.

Regional splanchnic blood flow (rSBF) was measured in rabbits with the radioactive microsphere technique. No statistically significant changes occurred in rSBF or vascular conductances in relation to the different states of the sleep-waking cycle (quiet-wakefulness, synchronized sleep, and desynchronized sleep).

Animals↗

Effects of experimental potassium depletion on renal function and urinary prostanoid excretion in normal women during hypotonic polyuria.

During hypotonic polyuria renal function studies by the clearance (cl.) method, and urinary PGE2, 6-keto-PGF1 alpha and TxB2 determinations were performed on 14 healthy women in normal potassium balance (N) and 14 healthy women in sustained potassium depletion (KD) induced by low dietary potassium intake (less than or equal to 10 mmol day-1) and natriuretic treatment. By using different depletive patterns, two groups with estimated cumulative potassium deficits of 160 +/- 43 mmol (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. (1) In both the KD1 and KD2 groups as compared to normal potassium balance (N), plasma potassium concentration and urinary potassium excretion were significantly lower; plasma renin activity was significantly higher. (2) Only in KD2 did significant changes appear in renal function and urinary prostanoid excretions. Besides a decrease in creatinine cl. and the urinary flow rate, an increase in fractional chloride excretion and a reduction in distal fractional chloride reabsorption were manifest. The plasma chloride concentration was reduced too. Urinary prostanoid excretions were significantly (6-keto-PGF1 alpha, TxB2) or tendentially (PGE2) lower. (3) Indomethacin treatment resulted in changes in mean arterial pressure (increase) and creatinine cl. (decrease) which were not significantly different in normal potassium balance and KD groups. Only in KD2 did the drug significantly reduce the fractional salt and water excretions and the fractional sodium and chloride deliveries to the diluting segments. However, indomethacin was unable to correct the inhibition of distal fractional chloride reabsorption. Therefore, the potassium depletion attained in the KD2 group was efficacious in depressing renal prostanoid synthesis. This fact, in the presence of high levels of angiotensin II, induced a reduction of the glomerular filtration rate thus contributing to renal ability to retain chloride and potassium.

Adult↗

Evaluation of the ileal absorption capacity for bile acids in the rabbit.

The intestinal absorption of bile acids has so far been studied from the measurement of the biliary secretion after their intestinal infusion. In the present investigation, the ileal absorption capacity for two different bile acids has been evaluated by means of an intestinal perfusion technique and the simultaneous blood drainage from the mesenteric vein corresponding to the isolated loop. Taurocholic acid and unconjugated cholic acid were infused at different concentrations (0.5-10.0 mM), at a flow rate of 4 ml/min/cm intest. Taurocholic acid absorption increased to a maximum with dose, then reaching a plateau, suggesting that a saturable process had taken place. Cholic acid uptake showed a saturable, possibly active, process, together with a nonsaturable one. These results are consistent with the physicochemical properties of the two bile acids. The technique seems so far suitable for the study of the intestinal absorption of substances undergoing the enterohepatic circulation, since it provides a direct measure of the absorbed fraction, without any distortion arising from the hepatic uptake and biliary secretion.

Animals↗

[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.

Adult↗

Uptake of bile acids by perfused rat liver: evidence of a structure-activity relationship.

The hepatic extraction of unconjugated and taurine-conjugated bile acids, provided with different hydrophilicity values, has been measured in the perfused rat liver, in order to evaluate the role of the bile acid structure and bile acid hydrophilicity on their uptake by the liver. Ursocholic, cholic, ursodeoxycholic and chenodeoxycholic acids, free and taurine-conjugated, were injected into the portal vein in dose response studies, using a nonrecirculating perfusion system. For all of the bile acids, the uptake process showed saturation. In addition, a nonsaturable component was apparent in bile acids provided with the lowest hydrophilicity values, as expressed by the lowest values of the water to octanol partition coefficient. The maximum uptake velocity increased with increasing values of the partition coefficient, which in turn were associated with 7-OH alpha to beta epimerization, the presence of 12-OH in alpha position and taurine conjugation. The ratio of maximum uptake velocity to Km (Km being the half-saturation constant) appeared to be markedly increased by taurine conjugation and by 7-OH alpha to beta epimerization, whereas it was reduced by the presence of 12-OH in alpha position.

Animals↗

Muscle blood flow changes during sleep as a function of fibre type composition.

In rabbits blood flow was measured in 19 muscles with the radioactive microsphere technique. Fibre type composition (SO, slow-twitch oxidative; FOG, fast-twitch oxidative-glycolytic; FG, fast-twitch glycolytic) was determined histochemically for the same muscles. While no significant changes occur in the transition from quiet wakefulness (QW) to synchronized sleep (SS), in desynchronized sleep (DS) blood flow decreases in SO and increases in FOG and FG fibres. These changes may be related to the changes in motor activity characteristic of DS: muscle atonia and twitches, respectively.

Animals↗

Antagonistic effects of sulpiride--racemic and enantiomers--on renal response to low-dose dopamine infusion in normal women.

In healthy women during moderate hydrosaline retention we have evaluated the antagonistic effects of sulpiride--enantiomers and racemic--on the renal action of a low-dose dopamine (DA) infusion (0.1 microgram/kg/min). The studies were performed, in hypotonic polyuria, by the clearance (C1) method in (1) hydrosaline retention (n = 23), (2) retention + dl-sulpiride (n = 8), (3) retention + d-sulpiride and (4) retention + l-sulpiride (in the latter two cases n = 7 subjects submitted to paired studies). Hydrosaline retention was induced by deoxycorticosterone acetate treatment. A common pattern of sulpiride treatment was applied. The DA renal hyperemia is abolished by l-sulpiride while it is transitorily attenuated by d-sulpiride. In both conditions 3 and 4 the increase in glomerular filtration rate, the inhibition of fractional isosmotic sodium reabsorption and the increase in urinary sodium excretion--induced by DA in condition 1--are suppressed. On the contrary, DA inhibition of fractional anisosmotic sodium reabsorption is not affected by sulpiride. The data indicate that DA renal hyperemia results from the action of DA on DA2 receptors; the DA inhibition of sodium transport by the diluting segments does not appear to be mediated by typical DA receptors.

Adult↗

[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.

6-Ketoprostaglandin F1 alpha↗

[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.

6-Ketoprostaglandin F1 alpha↗

[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.

Dinoprostone↗

[Further research on the role of prostanoids in controlling renal function in humans in normal potassium balance and acute experimental potassium depletion. II: Studies of potassium depletion].

The renal function was evaluated by clearance (cl.) method during hypotonic polyuria and successive relative antidiuresis induced by lysine-8-vasopressin (LVP) administration. Four 15 min and two 60 min 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. The study protocol was applied on 22 healthy women in acute potassium depletion obtained by natriuretic treatment combined with replacement on quantitative basis of net salt and water urinary losses either in normal potassium diet intake (50 meq/d) or in a low one (less than or equal to 10 meq/d). In Group D3 (n = 6) in the presence of a greater potassium cumulative deficit (198.4 +/- 22.2 meq), as compared to normal potassium balance, a significant reduction of kaliemia and a significant increase of PRA were present. During hypotonic poliuria, besides a marked renal potassium conservation, a significant decrease of creatinine cl., fractional chloride reabsorption (apparently at the diluting segments) and of urinary 6KPGF and TxB2 excretions, were observed. Urinary PGE2 excretion was n.s. reduced.

Acute Disease↗

[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.

Acute Disease↗

[Role of prostanoids in the control of renal function in normal potassium balance and in acute experimental potassium depletion. 4. Relation of extrarenal parameters, renal function parameters and urinary excretion of prostanoids].

The renal function has been evaluated by clearance (cl.) method during hypotonic polyuria and successive moderate antidiuresis induced by a low dose of lysine-8-vasopressin; four 15 min and two 60 min cl. periods were performed, 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 concentrations of PGE2, 6-keto-PGF1 alpha (6KPGF) and TxB2 were measured by RIA. The study protocol was applied in normal potassium balance and experimental potassium balance (KD), both in absence and presence of indomethacin. In KD groups with a potassium cumulative deficit of 198.4 +/- 22.2 meq (D3; n = 6) during polyuria significant correlations are consistent with the hypothesis that the lower the plasma potassium concentration is the higher the urinary chloride excretion and the inhibition of distal fractional chloride reabsorption. Moreover, by utilizing the polyuria and antidiuresis data pool, the effects of urine flow rate changes on PGE2 and 6KPGF urinary excretions are blunted as compared to normal potassium balance (n = 14). After indomethacin treatment (D3.I) the following functional relationships are disclosed: a) the lower the kaliemia is the lower the urinary chloride and potassium excretions and the higher the fractional isosmotic reabsorption; b) the lower the urinary potassium excretion is the lower the urinary chloride excretion. In both D3 and D3.I experimental groups the positive correlation between urinary chloride excretion and urinary potassium excretion is significant.

6-Ketoprostaglandin F1 alpha↗

Brain circulation during sleep and its relation to extracerebral hemodynamics.

Regional cerebral blood flow (rCBF) was measured in rabbits during the sleep-waking cycle, using radioactive microspheres. rCBF does not change significantly in the transition from wakefulness (W) to synchronized sleep (SS), while it significantly increases during desynchronized sleep (DS). No correlation was found between CBF changes and changes in cardiac output or regional blood flows in the transition from SS to DS. This suggests that the CBF increase in DS is not relevantly affected by changes in extracerebral hemodynamic factors.

Animals↗

Ultradian plasma corticotropin and cortisol rhythms: time-series analyses.

24-h plasma patterns of ACTH and cortisol were established in 6 subjects who had standard meals and in 4 subjects under continuous enteral nutrition. Temporal relationships between both hormones were analyzed. The individual assay data were subjected to time-series analyses to identify the periods of the oscillations in the plasma levels. The spontaneously occurring cortisol peaks were preceded by increases in ACTH levels, but z-score transformations clearly revealed that ACTH and cortisol were not quantitatively linked throughout the day. Individual subjects' power spectra gave evidence of a predominant periodicity in the oscillations of both hormones. These periodicities varied between individuals. They were 55-140 min for ACTH and 95-180 min for cortisol, indicating that, on occasion, a single cortisol peak may be initiated by two ACTH peaks. Cross spectral analysis of the individual data gave coherence spectra with a large peak which accounted for a substantial concordance of their period length, and cross variance spectra showed a consistent phase relationship between both hormones. These time series analyses applied to the data further support the concept that ACTH is the stimulating factor of cortisol release under basic conditions.

Activity Cycles↗

Effects of extracellular fluid volume changes on renal response to low-dose dopamine infusion in normal women.

Dopamine (DA) i.v. infused in a low dose (0.1 microgram/kg/min) in healthy women during sustained hypotonic polyuria, produced different renal functional effects as variations in extracellular fluid volume occurred. (1) In hydro-saline retention (n = 23), induced by desoxycorticosterone acetate treatment, DA produced typical vasodilator and hydro-natriuretic effects (Goldberg, 1972). (2) In hydro-saline depletion (n = 19), induced by diuretic treatment and low dietary sodium intake, DA lost its vasodilator and natriuretic efficacy, manifesting, on the other hand, renal sodium conserving effects mainly dependent on the increase in distal sodium reabsorption and a trend towards afferent arteriolar vasoconstriction. (3) Treatment with prazosin (n = 9) or propranolol (n = 9) in hydro-saline depletion, was efficacious in partly restoring the typical vasodilator and natriuretic effects of DA. Thus, in hydro-saline depletion, DA produced sympathomimetic effects which were sufficiently intense to outweigh those due to activation of specific DA renal receptors.

Adult↗