Biomedical subjects

A G Scicli

Publications and source records attributed to A G Scicli.

At least 73 records · Page 4Linked to original sources

PubMed1988

Renal hemodynamics in response to a kinin analogue antagonist.

The influence of endogenous kinins on renal hemodynamics was studied using a kinin analogue antagonist ([DArg0-Hyp3-Thi5-DPhe7-Thi8]bradykinin) in eight sodium-restricted anesthetized dogs. Clearance periods were run during intrarenal infusion of vehicle or 50 micrograms/min of analogue during normal and reduced renal perfusion pressure within (95 mmHg) and below (65 mmHg) the range of renal autoregulation. During normal renal perfusion, the analogue did not affect arterial pressure, glomerular filtration rate (GFR), or sodium excretion but decreased renal blood flow (RBF) by 20% (6.41 +/- 0.35 vs. 5.61 +/- 0.38 ml.min-1.g kidney wt-1, P less than 0.05) due to increased renal vascular resistance (RVR, 0.44 +/- 0.03 vs. 0.54 +/- 0.04 U, P less than 0.01). The analogue increased renin secretion rate (RSR, 311 +/- 190 vs. 654 +/- 202 ng angiotensin I/min, P less than 0.001). With reduced renal perfusion (95 mmHg), RBF was unchanged, and sodium excretion and RVR decreased. Vehicle did not change GFR, but the analogue abolished autoregulation of GFR (-37%, P less than 0.02) and decreased filtration fraction (24 +/- 4 vs. 34 +/- 4%, P less than 0.05). Renal perfusion pressure of 65 mmHg decreased RBF, GFR, and sodium excretion similarly with vehicle or analogue. Converting-enzyme inhibition eliminated the changes in RVR. Thus kinin antagonism increased RSR and consequently RVR at normal renal perfusion. As renal perfusion pressure decreased, kinin antagonism diminished autoregulation of GFR but not of RBF. These results suggest that kinin antagonism may either modify the arteriolar resistance or alter the coefficient of filtration, resulting in decreased GFR at reduced renal perfusion pressure.

Animals↗

PubMed1988

Influence of kinins and angiotensin II on the regulation of papillary blood flow.

The influence of kinins and angiotensin II on the regulation of renal cortical and papillary blood flow and sodium and water excretion was examined in rats. Superficial cortical and papillary blood flows were measured using a laser-Doppler flowmeter. Papillary blood flow increased 50% after enalaprilat (60 micrograms/kg) and phosphoramidon (5.5 micrograms.kg-1.min-1) were given along with 0.3 M sodium bicarbonate solution to inhibit degradation of kinins and enhance urinary kallikrein activity. Infusion of a kinin antagonist, D-Arg-Hyp-Thi-D-Phe-bradykinin (5 micrograms/min), returned papillary blood flow to control levels. Urine flow and sodium excretion increased after the administration of the kininase inhibitors and sodium bicarbonate, while glomerular filtration rate (GFR) and outer cortical blood flow were unaltered. The kinin antagonist did not alter sodium and water excretion in rats receiving the kininase inhibitors and bicarbonate. Administration of the kinin antagonist alone lowered papillary blood flow by 20%, without affecting outer cortical blood flow or GFR. Urine flow decreased and urine osmolality increased after the rats received the kinin antagonist, but sodium excretion remained unaltered. To assess the role of angiotensin II in the control of papillary blood flow, kinin receptors were blocked by infusion of an antagonist, and the effects of enalaprilat and saralasin were studied. Papillary blood flow increased after blockade of the angiotensin II system in rats receiving the kinin antagonist. These results indicate that the kallikrein-kinin and renin-angiotensin systems participate in the regulation of papillary blood flow.

Angiotensin II↗

PubMed1988

Effects of a kinin antagonist on mean blood pressure.

Administration of high doses of a kinin antagonist produces an increase in blood pressure. Thus, endogenous kinins may be involved in the regulation of blood pressure. Kinins can induce the release of vasoactive substances such as catecholamines, renin, vasopressin, histamine, and prostaglandins. To determine whether the blood pressure changes induced by high doses of kinin antagonist are due to agonistic activity mediated by these vasoactive substances, we studied the effect on blood pressure of a kinin antagonist (DArg0-Hyp3-Thi5,8-DPhe7-bradykinin) administered to control, nephrectomized, and adrenalectomized rats, and to rats treated with vasopressin V1-receptor antagonist, ganglionic and alpha- and beta-adrenergic receptor blockers (either separately or combined), histamine H1- and H2-receptor blockers, and indomethacin, a prostaglandin synthesis inhibitor. Blood pressure changes were monitored on awake, restrained rats. In the control rat, the kinin antagonist injected as a bolus (4 mg/kg) into the ascending aorta produced a transient biphasic blood pressure response, first a pressor effect (delta BP = 7 +/- 1 mm Hg; p less than 0.05), then a depressor effect (delta BP = -20 +/- 6 mm Hg; p less than 0.05). The pressor response to the kinin antagonist was not affected by any of the treatments; however, the depressor effect of the kinin antagonist appeared to be caused by the release of vasodilator prostanoids from the kidney, since it was not observed in the nephrectomized rats or in those treated with indomethacin. The pressor effect induced by the kinin antagonist suggests that kinins may contribute to the regulation of blood pressure.

Adrenal Glands↗

PubMed1988

Effect of a kinin antagonist on the acute antihypertensive activity of enalaprilat in severe hypertension.

The purpose of this study was to assess the role of kinins in the acute antihypertensive effect of the converting enzyme inhibitor (CEI) enalaprilat in rats with severe hypertension induced by aortic ligation between both renal arteries. For this study, we used a bradykinin analogue, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-DPhe-Thi-Arg-TFA, with in vivo antagonistic properties. Hypertensive rats were infused intra-aortically for 15 minutes with either saline (30 microliters/min) or the kinin antagonist (40 micrograms/kg/min). Five minutes after the infusion was begun, a bolus injection of enalaprilat (60 micrograms/kg) was given. The blood pressure of the saline-infused animals decreased 48 +/- 6 mm Hg (from 180 +/- 7 to 132 +/- 7 mm Hg), while that of the rats treated with the antagonist decreased only 21 +/- 4 mm Hg (from 175 +/- 3 to 154 +/- 3 mm Hg). The difference between both decrements was significant (p less than 0.01). In another group of hypertensive animals (n = 9), we measured kinin concentration in plasma from arterial blood before and after administration of CEI (41 +/- 10 vs 68 +/- 20 pg/ml, respectively; NS). These results are consistent with the hypothesis that kinins play a role in the acute antihypertensive effect of CEIs in rats with severe hypertension. However, since arterial blood kinin concentrations were not increased significantly after CEI administration, the effect of the CEI may be due to an increase in tissue kinins, which could act as autacoids regulating vascular resistance.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1988

Kinins paracrine hormone.

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Angiotensin-Converting Enzyme Inhibitors↗

PubMed1987

Excess antibody immunoassay for the measurement of tonin in rat tissues and plasma.

Tonin, a proteolytic enzyme isolated from the rat submandibular gland, can generate angiotensin II directly from angiotensinogen. To date a method for the measurement of tonin in plasma has not been available and the present paper describes a sensitive and specific excess antibody immunoassay for determination of tonin in tissue homogenates and plasma. Interference from immunologically cross-reacting proteins was evaluated and the assay was found to be specific for tonin. Tonin measured in various tissue homogenates was directly proportional to the amount of sample added, giving a linear dose-response curve. The slope of this curve was determined by the recovery of tonin, which was better than 55% for urine and all tissues tested. The highest concentration of tonin was seen in the submandibular and sublingual gland (69 and 0.7 microgram/mg protein, respectively). The parotid gland, the exorbital lacrimal gland, liver, kidney, pancreas, and lung contained only negligible amounts (less than 4 ng/mg protein). Tonin in plasma was bound to one major inhibitor with a molecular weight of about 650,000-750,000. A partial splitting of the tonin-inhibitor complex was obtained by preincubating plasma with guanidine, allowing tonin to be measured with a recovery of 38 +/- 13% (n = 16) and with a linear dose-response curve. The concentration of immunoreactive tonin in normal arterial plasma from adult male rats was 0.90 +/- 0.53 ng/ml (n = 16). The concentration decreased after removal of the submandibular glands and increased after sympathetic stimulation.

Animals↗

PubMed1987

T-kininogen in rat plasma after nephrectomy and other surgical traumas.

Plasma kininogen is known to increase after nephrectomy in the rat, and we studied the type of kininogen responsible for the increase. Total kininogen in plasma was estimated by measuring the kinins released after incubation with an excess of trypsin, and expressed as micrograms bradykinin equivalents per ml of plasma (bk eq/ml). Plasma Kininogen in 24-hournephrectomized rats increased five-fold over the control values (16.4 +/- 0.8 vs 3.0 +/- 0.3 micrograms bk eq/ml; p less than 0.001). However, we found that the increase in total kininogen was not due to nephrectomy per se, but rather to surgery, since similar increases were found after 24 hours in shamnephrectomized rats (15.5 +/- 0.5 micrograms bk eq/ml), and in rats with a catheter implanted into the carotid artery (14.2 +/- 1.7 micrograms bk eq/ml). The increase in kininogen was proportional to the extent of the surgery since simple exposure of the carotid artery increased kininogen to 5.3 +/- 0.5 micrograms bk eq/ml, and sham carotid cannulation to 8.3 +/- 0.4 micrograms bk eq/ml. Anesthesia without surgery did not affect plasma kininogen concentration. To determine whether the adrenals or the pituitary glands are involved in mediating the changes, plasma kininogen was measured after adrenalectomy and hypophysectomy. Total kininogen in plasma of 24 hour-adrenalectomized rats was sevenfold higher than that of intact rats, also higher than the total kininogen in plasma of sham-adrenalectomized rats (21.6 +/- 1.7 vs. 16.5 +/- 1.1 micrograms bk eq/ml; p less than 0.05). The role of the hypophysis was studied by nephrectomizing rats 12 days after they had been hypophysectomized. Total plasma kininogen in the control group of rats was still four-fold higher than in intact rats. Twenty-four hours after nephrectomy, a further two-fold increase was obtained (12.7 +/- 1.6 vs. 25.6 +/- 2.0 micrograms bk eq/ml; p less than 0.001). Kinins released by trypsin from plasma of the various groups of rats were separated by reserve-phase (C18) high pressure liquid chromatography (HPLC), and then quantitated. Only T-kinin was found to be increased. Unknown kinins, which were partially converted to T-kinin by increasing trypsin concentration from 10 to 80 mg/ml plasma, were also found by HPLC. The results indicate that surgical trauma induces a marked increase in the concentration of T-kininogen in rat plasma. Neither the hypophysis, nor the adrenals seem to be involved in mediating the increase in T-kininogen.

Animals↗

PubMed1987

Competitive analog antagonists of bradykinin in the canine hindlimb.

Six structural analogs of bradykinin were tested to determine whether they antagonize the vasodilator response to bradykinin. The dog hindlimb preparation was used as a bioassay. Mongrel dogs were anesthetized and the femoral arteries were isolated and fitted with a noncanulating electromagnetic flow probe. An indwelling catheter was also placed for administration of saline, bradykinin, or the various analogs. The vasodilatory responses of the hindlimb circulation to bolus doses of bradykinin from 1 of 20 ng were tested during vehicle or analog administration at 1 and 10 micrograms/min. Bradykinin analogs which were characterized by amino acid replacement by beta-(2-thienyl)-L-alanine (Thi) at positions 5 and 8, D-phenylalanine (D-Phe) at position 7, and an additional replacement of hydroxyproline at position 2 or 3 were effective antagonists of bradykinin. The decapeptide bradykinin analog (BKA06) D-Arg-(Hyp3-Thi5-D-Phe7-Thi)-BK was the most potent analog tested, producing a full log dose shift in the dose-response curve to bradykinin at the 10 micrograms/min (4 nmole/min) infusion rate. None of the analogs we tested produced vasodilation or had any effect upon systemic blood pressure at the concentrations tested. Our results suggest that these structural analogs of bradykinin may be effective pharmacologic tools to study the role of endogenous kinins in the control of vascular resistance and circulatory homeostasis.

Amino Acid Sequence↗

PubMed1986

Identification of a new kinin in human urine.

The types of kinins excreted in fresh urine of dogs, rats, and humans were compared. Urinary kinins were separated by reverse-phase (C18) high performance liquid chromatography and quantitated by radioimmunoassay using an antibody directed against the COOH-terminal region of the peptide. Kinins were found in the following proportions: 53 +/- 3% bradykinin, 23 +/- 4% Lys-bradykinin, and 13 +/- 7% des-Arg1-bradykinin in dog urine; 67 +/- 6% bradykinin, 6 +/- 3% Lys-bradykinin, and 10 +/- 3% des-Arg1-bradykinin in rat urine; and 12 +/- 4% bradykinin, 30 +/- 3% Lys-bradykinin, 2 +/- 1% des-Arg1-bradykinin, and 41 +/- 3% unknown kinin in human urine. The unknown kinin was purified from a pool of human urine. Amino acid sequencing revealed a structure similar to Lys-bradykinin except that proline in position 4 was replaced by alanine ([Ala3]Lys-bradykinin). Synthetic and endogenous [Ala3]Lys-bradykinins had similar high performance liquid chromotography elution volumes and both had vasodilator activity and contracted the rat uterus. Human urinary kallikrein incubated with semipurified human low molecular weight kininogen released 76% of the total kinins as Lys-bradykinin, 7% as bradykinin, and 17% as [Ala3]Lys-bradykinin. In contrast, rat urinary kallikrein released 86% bradykinin, 18% Lys-bradykinin, and negligible amounts of [Ala3]Lys-bradykinin. The study revealed the presence of a new kinin, [Ala3]Lys-bradykinin, in human urine and it also proves that the types of kinins generated intrarenally are species-dependent.

Amino Acid Sequence↗

PubMed1986

Purification and characterization of a serine protease (esterase B) from rat submandibular glands.

A new protease has been purified to homogeneity from rat submandibular gland homogenate by using DEAE-Sephadex chromatography, chromatofocusing, aprotinin-Sepharose affinity chromatography, and high-performance liquid chromatography. The enzyme has been named esterase B, since it represents the second major esterolytic peak on DEAE-Sephadex chromatography of submandibular gland homogenate. It is an acidic protein (pI = 4.45) with an apparent molecular weight of 27 000. It is heat-stable and has an optimum pH of 9.5. Esterase B hydrolyzed the synthetic substrates tosyl-L-arginine methyl ester and Val-Leu-Arg-p-nitroanilide (S2266). It also cleaved dog plasma kininogen to produce a kinin, identified as bradykinin on reverse-phase high-performance liquid chromatography. Esterase B, however, is only a weak kininogenase, since it had only 5% of the kininogenase activity of equimolar concentrations of glandular kallikrein and had no effect on rat mean blood pressure or on the isolated rat uterus. Esterase B activated plasminogen and had caseinolytic activity. It was inhibited by aprotinin, soybean trypsin inhibitor, lima bean trypsin inhibitor, phenylmethanesulfonyl fluoride, antipain, leupeptin, and p-tosyl-L-lysine chloromethyl ketone. On double immunodiffusion, when reacted with kallikrein and tonin antisera, esterase B showed partial identity with kallikrein but not with tonin. On immunoelectrophoresis against kallikrein antisera, esterase B formed a precipitin arc at a position different from that of kallikrein. Esterase B appears to be a trypsin-like serine protease having some homology with glandular kallikrein.

Amino Acids↗

PubMed1986

Characterization of monoclonal antibodies against rat glandular kallikrein.

Monoclonal antibodies can be produced in large amounts, are homogenous and can be highly purified. A specific monoclonal antibody against glandular kallikrein could be very useful in studies of the kallikrein-kinin system, both in vivo and in vitro. Two monoclonal antibodies against rat glandular kallikrein (rgKK) were produced by immunized mouse spleen and lymph node fusion with myeloma Ag8.653. Both antibodies, named 2E9.8 and 2E9.9, bound active 125I-kallikrein and phenylmethylsulfonyl fluoride (PMSF)-inactivated 125I-kallikrein. A radioimmunoassay (RIA) was developed with each of the antibodies using rabbit anti-mouse gamma globulin to separate bound from free 125I-rgKK. The standard curve (range 10-1000 ng/tube) was curved even when subjected to logit-log transformation. Using 3% polyethylene glycol (PEG) to assist separation of bound from free, the standard curve became straight for 2E9.8 and the RIA was more sensitive, with a binding range of 0.35-2.4 ng/tube. Both antibodies were specific for rgKK since they had negligible cross-reaction with purified proteases from the submandibular gland of the rat (tonin, esterases B and E). They did not cross-react with mouse nerve growth factor, epidermal growth factor, nor with pig pancreatic kallikrein. Antibody 2E9.9 did appear to bind some human kallikrein when tested with high concentrations of this enzyme, while 2E9.8 did not. When preincubated with purified rgKK, both antibodies prevented the enzyme from releasing kinins from semi-purified dog kininogen and from cleaving [3H]-L-arginine methyl ester (3H-TAME). These results suggested that both antibodies bind an epitope near to, and maybe including, the active site of the enzyme. Monoclonal antibody 2E9.8 appears to be specific for rgKK, can be used in a sensitive RIA, and is capable of inhibiting the enzymatic activity of kallikrein. It should prove to be useful in vivo for examining the role of kallikrein in physiological processes.

Animals↗

PubMed1986

Purification and characterization of canine urinary kallikrein.

The renal kallikrein-kinin system may play a role in the regulation of sodium and water balance. Although the dog is a frequently used experimental animal in the study of the renal kallikrein-kinin system, dog urinary kallikrein (DUKK) has been poorly studied. We have purified DUKK by a series of chromatographic and electrophoretic procedures including anion-exchange chromatography, filtration through p-aminobenzamidine-Sepharose (to remove contaminating nonkallikrein esterases), gel filtration, isoelectric focusing, and molecular sieve HPLC. This DUKK preparation gave three protein bands on polyacrylamide gel electrophoresis, each having similar esterolytic and kininogenase activities and immunological identity. Preparative isoelectric focusing indicated the presence of multiple forms of kallikrein with pI's of 3.93, 4.05, 4.24, and 4.44, the species with a pI of 4.24 constituting the major component. Neuraminidase treatment converted all of the forms into the component with a pI of 4.44, suggesting the charge heterogeneity was due mainly to differences in sialic acid content. DUKK has a specific activity of 3 mg bradykinin eq/min/mg protein when partially purified dog kininogen is used as a substrate. It is a glycoprotein with a molecular weight of 40,500 (amino acid analysis best fit method) and an alkaline pH optimum (9.0-9.5). DUKK is resistant to soybean trypsin inhibitor and lima bean trypsin inhibitor but is inhibited by several serine protease inhibitors such as antipain, leupeptin, and p-aminobenzamidine. Phe-Phe-Arg-chloromethyl ketone is a very potent inhibitor of DUKK. Contrary to previous reports, DUKK is also inhibited by N-alpha-p-tosyl-L-lysine chloromethyl ketone and aprotinin, the inhibition by the latter being inversely related to the concentration of NaCl in the medium. The esterolytic and amidolytic activities of DUKK are inhibited by an increase in NaCl concentration of the medium. This inhibition may be related to a NaCl-induced conformational change in the enzyme moiety.

Animals↗

PubMed1986

Kininogenase from rat vascular tissue.

A kininogenase resembling glandular kallikrein was partially purified from vascular tissue and characterized. Saline perfused rat tail arteries and veins were homogenized in 0.25 M sucrose containing 10 mM Tris-HCl (pH 7.4). The homogenate was centrifuged at 105,000 X g for 60 min and a vascular kininogenase was purified from the supernatant by chromatofocusing, affinity chromatography on immobilized antibodies against rat urinary kallikrein, and gel filtration on Sephadex G-100. The inhibitory effects of antibodies against rat urinary kallikrein were tested using equivalent kinin-forming concentrations of rat urinary kallikrein and vascular kininogenase. Kininogenase activities of both enzymes were similarly inhibited by urinary kallikrein antibodies. Aprotinin (1,000 KIU) completely inhibited vascular kininogenase activity while soybean trypsin inhibitor (100 micrograms) did not modify its kinin-forming activity. Vascular kininogenase and rat urinary kallikrein had the same elution volume when chromatographed on a Sephadex G-100 column and had similar mobilities in 10% polyacrylamide gel electrophoresis. Kinins released by vascular kininogenase were identified as bradykinin by reverse-phase high performance liquid chromatography. Rat vascular kininogenase appears to be similar to glandular kallikrein. Kinins released locally by vascular kininogenase may contribute to the regulation of vascular tone.

Animals↗

PubMed1986

Renal kallikrein-kinin system.

In the last decade, our knowledge of the renal kallikrein-kinin system has been advanced significantly. More specific and sensitive methods for assessing its activity have been developed. Further, it has been found that in the kidney this system is localized in the distal nephron, where it appears to be linked to processes that control water and electrolyte excretion. Data indicate that the kallikrein-kinin system interacts with other renal hormonal systems such as the prostaglandin and renin-angiotension-kinin system may participate in the control of renal function and the pathophysiology of renal diseases. An increase in kallikrein excretion has been observed after administration of antihypertensive drugs. The kallikrein-kinin system may therefore participate in their mechanism(s) of action. Our current knowledge suggests that the renal kallikrein-kinin system is an integral part of the intrarenal hormonal system that controls water and electrolyte excretion and participates in the regulation of blood pressure.

Animals↗

PubMed1986

Immunocytochemical localization of renin and kallikrein in the rat renal cortex.

Immunocytochemical studies in the past, using alternate serial sections to localize individual antigens, concluded that there was no close relationship between renin- and kallikrein-containing structures in the rat kidney. We have investigated this relationship by simultaneously localizing renin and kallikrein in the same section using immunoperoxidase with two different chromogens. Analysis of serial kidney sections from three rats indicated that kallikrein-containing late distal tubular cells corresponded in their distribution to connecting tubule cells. They were observed in the proximity (less than 3 micrograms) of renin-containing JG cells in 66.6% of the superficial (N = 30), 46.6% of the midcortical (N = 15) and 26.7% of the juxtamedullary (N = 15) afferent arterioles surveyed. When traced through serial sections, 90% of the afferent arterioles from superficial glomeruli (N = 30), 86.7% of the afferent arterioles from midcortical glomeruli (N = 15) and 73.3% of those from juxtamedullary glomeruli (N = 15) came within 3 micrograms of a late distal tubule showing some kallikrein-positive cells. These cells were adjacent to the afferent arteriole in 67 to 80% of the arterioles surveyed. This spatial relationship suggests an anatomical basis for a possible interaction between the afferent arteriole, containing renin-positive JG cells, and kallikrein-positive late distal tubular cells.

Animals↗

PubMed1986

Effect of DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid on the blood pressure response to vasoactive substances.

The importance of kininase I (carboxypeptidase N) in the catabolism of circulating kinins is not known. DL-2-Mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGTA) has been reported to be an inhibitor of kininase I both in vitro and in vivo. In order to evaluate the possible role of kininase I in the in vivo inactivation of bradykinin, the authors studied the blood pressure responses of pentobarbital-anesthetized rats to bradykinin before and after the i.v. administration of MGTA (a 10-mg/kg bolus followed by 1 mg/kg/min continuous infusion). MGTA potentiated bradykinin-induced hypotension. The specificity of MGTA for kininase I was tested using other peptide and nonpeptide vasoactive substances. MGTA potentiated the hypertension due to angiotensin I, angiotensin II and vasopressin, but it did not affect the response to phenylephrine. On the other hand, MGTA did not potentiate the hypotensive action of acetylcholine, but it did potentiate that of sodium nitroprusside. The potentiation of bradykinin-induced hypotension is compatible with inhibition of kininase I by MGTA. The data suggest, however, that MGTA is not selective for any enzyme that inactivates kinins, inasmuch as other peptides and nonpeptide vasoactive substances are also potentiated.

3-Mercaptopropionic Acid↗

PubMed1985

Effects of synthetic atrial natriuretic factor in the isolated perfused rat kidney.

It is known that atrial extracts (AE) and synthetic atrial natriuretic factor (ANF) can increase glomerular filtration rate (GFR) and electrolyte and water excretion both in vivo and in vitro. It is not clear, however, if ANF-induced increases in filtered load (increased GFR) are required to produce natriuresis and diuresis. We perfused isolated rat kidneys with AE or synthetic ANF at constant pressure in a single-pass system. Extracts of atrial tissue (1 mg/ml) and high concentrations of ANF (31 and 61 ng/ml) significantly increased both GFR and electrolyte and water excretion. During continued infusion of ANF, GFR stabilized at increased levels, but sodium and water excretion continued to increase. After the termination of infusions, GFR and potassium excretion returned to control levels, but sodium and water excretion remained significantly elevated. Infusion of a low concentration of ANF (3 ng/ml) significantly increased sodium and water excretion without changing either GFR or potassium excretion. We conclude that increases in GFR are not a prerequisite for natriuresis and diuresis in response to ANF, but that increases in GFR can potentiate the response. Furthermore, our data suggest that ANF increases potassium excretion only if it increases GFR.

Animals↗

PubMed1985

Effect of urinary alkalinization on the intrarenal formation of kinins.

Alterations in the urinary excretion rate of kallikrein (UKKV) have frequently been assumed to reflect alterations in the intrarenal generation of kinins. Since other factors such as urinary pH and the activity of renal kininases may affect the intrarenal concentration of kinins, we investigated the effect of urinary alkalinization on kinin excretion in the presence and absence of kininase II inhibition. Urine was collected from the ureters of rats during control (ctl) (0.15 M NaCl infusion) and experimental (exp) periods. During exp periods, group I (time control) was infused with 0.15 M NaCl, group II with 0.3 M NaCl, and groups III and IV with 0.3 M NaHCO3, all at 0.12 ml/min. Prior to the ctl period, group IV was pretreated with the kininase II inhibitor captopril (40 mg/kg). During the exp period, urinary kinin excretion (UKiV) increased significantly in all groups ([exp - ctl] UKiV = 21 +/- 7, 27 +/- 9, 52 +/- 14, and 70 +/- 9 pg X min-1 X kg-1 in groups I, II, III, and IV, respectively). Urinary pH increased significantly in groups II, III, and IV. The increases in UKiV and pH were significantly greater in the bicarbonate-infused rats than in control. Partial correlation coefficients show that UKiV correlates with a high degree of significance only with urinary pH (r = 0.6). During the ctl period, UKiV in the captopril-pretreated rats was not different from that in other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗