Browsing by Author "ROBLERO, JS"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
- ItemBLUNTING EFFECT OF PEPSANURIN INTRODUCED IN THE DUODENUM ON THE ATRIAL-NATRIURETIC-PEPTIDE DIURETIC ACTION IN RATS(1993) CROXATTO, HR; BORIC, MP; ROBLERO, JS; ALBERTINI, RPepsanurin (PU) is a peptide(s) obtained by pepsin hydrolysis of human plasma or its globulin fraction. We have reported that the accelerated renal excretory rate induced by atrial natriuretic peptide (ANP) can be considerably blunted by PU either in the intact rat or in the isolated perfused rat kidney. We explored whether or not PU can be part of a signaling mechanism originated in the digestive tract, involved in the regulation of water and electrolyte homeostasis. PU obtained either from human (0.5 ml) or rat plasma (0.25-0.5 ml) administered into the duodenal lumen of rats, counteracted significantly the diuretic-saluretic action ot a 0.5- mug bolus of ANP, reproducing qualitatively the effect of its intraperitoneal administration. Human PU reduced the ANP-stimulated renal excretion by 67-90% for Na (P < 0.001) and by 35-54% for water (P < 0.02-P < 0.001); the inhibition induced by rat PU was 45-96% for Na (P < 0.05-P < 0.01) and 35-65% for water (P < 0.05-P < 0.01). Rat PU (0.5 ml) abolished the rise of glomerular filtration rate induced by ANP without affecting fractional Na excretion. All the samples tested decreased K excretion, but in some experiments, the difference did not reach statistical significance. Contrary to the effect of PU, the introduction in the duodenum of (i) isotonic glucose solution, (ii) hydrolysate of bovine serum albumin, or (iii) hydrolysate of casein prepared after the same procedure yielding PU from plasma failed to produce an inhibition of the ANP stimulation of renal excretory rate. In addition, human plasma incubated at 37-degrees-C for 24 to 48 hr, prior to pepsin digestion, did not yield PU, which indicates that PU is generated from a substrate sensitive to endogenous enzymes and/or that its stability is vulnerable to endogenous enzymes.
- ItemINHIBITION OF ATRIAL-NATRIURETIC-PEPTIDE INDUCED NATRIURESIS BY PLASMA HYDROLYSATES CONTAINING PEPSANURIN(1992) BORIC, MP; CROXATTO, HR; ALBERTINI, R; ROBLERO, JSThe specificity of antidiuretic actions of pepsanurin, a peptidic fraction obtained by pepsin hydrolysis of plasma, was studied in anesthetized rats and in isolated perfused rat kidneys. Pepsanurin was obtained from fresh dialyzed human plasma digested with pepsin (2,400 units/ml, 18 hours at 37-degrees-C, pH 2.5), deproteinized (10 minutes at 80-degrees-C), and centrifuged. In the rat, intraperitoneal injections of pepsanurin (0.5 ml/100 g body wt) significantly inhibited the effects of an intravenous bolus of atrial natriuretic peptide (ANP) (0.5-mu-g) on water, sodium, and potassium excretion without altering systemic blood pressure. In addition, pepsanurin abolished the peak in glomerular filtration rate and reduced the ANP-induced rise in fractional sodium excretion. Pepsanurin also inhibited the natriuretic effects of amiloride (10-mu-g/100 g body wt i.v.) without changing glomerular filtration rate, but it did not inhibit the potassium-retaining effect of amiloride. In contrast, pepsanurin had no effect on basal urinary excretion, and it did not affect the diuretic response induced by furosemide (doses of 25, 50, or 100-mu-g i.v.). Control peptidic hydrolysates prepared from human plasma preincubated 48 hours at 37-degrees-C (PIPH), bovine albumin (BSAH), or human albumin did not inhibit ANP, amiloride, or furosemide. In perfused kidneys, pepsanurin significantly and reversibly reduced sodium and water excretion. Furthermore, pepsanurin, but not PIPH or BSAH, blocked the natriuretic and diuretic effects of ANP. These results support the existence of a specific plasma substrate able to release a peptide or peptides that counteract distal tubule diuresis and natriuresis by an intrarenal mechanism.
- ItemKALLIKREIN-KININ AND RENIN-ANGIOTENSIN SYSTEMS IN RENOVASCULAR HYPERTENSION IN RATS(1980) VIO, CP; ROBLERO, JS; CROXATTO, HRPlasma renin activity (PRA) and the levels of urinary kallikrein (UK) were studied simultaneously in Goldblatt 1- and 2-kidney hypertensive rats (1KG and 2KG) 5, 10 and 15 wk after clamping the left renal artery. Increase in PRA was statistically significant in 2KG rats (P < 0.0005 on the 5th and 10th wk, and P < 0.002 on the 15th wk). PRA was not significantly different to that of controls in 1KG rats. The urinary kallikrein levels were significantly lower in 1KG rats (P < 0.002) in relation to values found in normotensive rats. In 2KG rats, urinary kallikrein levels became significantly lower than those in controls only 15 wk after surgery.
- Item[N-METHYL-TYR1, N-METHYL-ARG7-D-LEU8]-DYNORPHIN-A-(1-8) ETHYLAMIDE, A STABLE DYNORPHIN ANALOG, PRODUCES DIURESIS BY KAPPA-OPIATE RECEPTOR ACTIVATION IN THE RAT(1992) SALAS, SP; ROBLERO, JS; LOPEZ, LF; TACHIBANA, S; HUIDOBROTORO, JPThe i.v. administration of E-2078 {[N-methyl-Tyr1-N-methyl-Arg7-D-Leu8]-dynorphin-A-(1-8) ethylamide} to conscious animals in doses of 15, 50 or 200-mu-g/rat caused a dose-related diuretic response associated with a significant in crease in glomerular filtration rate (GFR) and in blood pressure. The overall excretion of Na+ was not modified by the opioid, whereas it reduced K+ output and its fractional excretion. Time course studies demonstrated that the increase in GFR and in blood pressure were transient and did not parallel the changes in urine outflow. Pretreatment of the animal with 1 mg/kg of naltrexone or of naloxone reduced the pressor response but did not reduce the renal action of E-2078. Doses of naltrexone 10 times larger (10 mg/kg) were required to attenuate the diuretic effect and abolish completely the changes in K+ excretion; however, the increase in GFR was not antagonized by 10 mg/kg of naltrexone. Consonant with the studies in conscious rats, perfusion of isolated rat kidneys with 0.2 to 1.8-mu-M E-2078 increased urine flow in a dose-dependent manner, and this effect was prevented by the simultaneous perfusion of 2-mu-M naltrexone with the peptide. In pentobarbital-anesthetized animals, E-2078 elicited a diuretic response that was not parallelled by changes in GFR or electrolyte excretion. In addition, E-2078 caused a long-lasting decrease in blood pressure which was blocked completely by pretreatment of the animal with 1 mg/kg of naltrexone. The diuretic effect of E-2078 was not modified by pretreatment of the animals with beta-funaltrexamine. Rats anesthetized with ether or halothane also showed a decrease in blood pressure after E-2078. Anesthesia with ether or halothane attenuated or anulled the pressor action of bremazocine or U-50,488, whereas barbiturate anesthesia resulted in a precipitous and prolonged hypotension. These results suggest that the stable dynorphin analog, E-2078, produces its effects on urinary excretion primarily via a kappa receptor mediated mechanism.
- ItemRELEASE OF RENAL KALLIKREIN TO PERFUSATE BY ISOLATED RAT-KIDNEY(1976) ROBLERO, JS; CROXATTO, HR; ALBERTINI, RB
- ItemURINARY KALLIKREIN ACTIVITY DURING RAT PREGNANCY(1987) SALAS, SP; ROBLERO, JS; CROXATTO, HR; VALDES, GChanges in urinary kallikrein activity and its possible correlation with changes in blood pressure and renal excretory function during pregnancy were studied in the rat. To establish a possible physiological role of kallikrein in this condition aprotinin, which inhibits kallikrein as well as other serine protease was administered to pregnant rats. Urinary kallikrein activity was markedly increased during pregnancy and correlated positively with urine volume and electrolytes excretion, but not with blood pressure. Aprotinin administration almost completely inhibited kallikrein activity, however, blood pressure levels, urine volume and electrolytes were not changed after one day of aprotinin treatment. In conclusion, although renal kallikrein is highly enhanced during pregnancy, its physiologic role in this condition remains elusive.