Dietary habits affect fatty acid composition of visceral adipose tissue in subjects with colorectal cancer or obesity.

PURPOSE: Aim of this study was to identify a possible relationship among dietary fatty acids (FA) intake, FA adipose tissue (AT) profile and cancer condition in lean vs obese subjects affected or not by colorectal cancer (CRC). Actually, inadequate dietary habits together with physical inactivity are primary determinants of obesity and cancer risk. Changes in lipid metabolism play a crucial role in different types of cancer and key enzymes involved in lipid-metabolic pathways, such as stearoyl-coA-desaturase 1 (SCD-1), are differentially expressed in normal and cancer tissues. METHODS: Food frequency questionnaires (FFQ) were analyzed by Winfood software. FA were assessed by gas-liquid chromatography in visceral AT samples. Estimated desaturase activities were calculated as precursor FA/product FA ratio. Desaturase gene expressions were evaluated by RT-qPCR. RESULTS: Lean and obese CRC subjects showed inadequate dietary habits. In particular, lean CRC subjects showed increase in the intake of saturated FA, specifically palmitic (p = 0.0042) and stearic acid (p = 0.0091), and a corresponding reduction of monounsaturated FA consumption, in particular oleic acid (p = 0.002) with respect to lean without CRC. Estimated SCD-1 activity in AT was increased in all the groups vs lean without CRC (pANOVA = 0.029). CONCLUSIONS: Unhealthy eating habits, characterizing obese and CRC subjects, may influence the visceral AT profile and contribute to the alteration of the metabolic pathways. The quality of the diet, other than the quantity, can have a main role in the establishment of inflammatory microenvironment and in metabolic changes favouring CRC.

Consumption of extra-virgin olive oil rich in phenolic compounds improves metabolic control in patients with type 2 diabetes mellitus: a possible involvement of reduced levels of circulating visfatin.

AIM: Phenolic compounds naturally contained in extra-virgin olive oil (EVOO) have demonstrated anti-inflammatory and antioxidant properties. The present study aimed at evaluating the effects of a polyphenol-rich extra-virgin olive oil (EVOO) (high-polyphenol EVOO, HP-EVOO) on the metabolic control and the production of specific pro-/anti-inflammatory adipokines in overweight patients with type 2 diabetes mellitus (T2D). METHODS: Eleven overweight T2D patients not in treatment with insulin were invited to follow their habitual diet for a total of 8 weeks. During the first 4 weeks (wash-out period), they were asked to consume refined olive oil (ROO, polyphenols not detectable) and then to replace ROO with HP-EVOO (25 mL/day, 577 mg of phenolic compounds/kg) for the remaining 4 weeks. Anthropometric parameters, fasting glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein, plasma lipid profile, liver function and serum levels of TNF-α, IL-6, adiponectin, visfatin and apelin were assessed at the end of each 4-week period. RESULTS: HP-EVOO consumption significantly reduced fasting plasma glucose (P = 0.023) and HbA1c (P = 0.039) levels as well as BMI (P = 0.012) and body weight (P = 0.012). HP-EVOO ingestion determined a reduction in serum level of aspartate aminotransferase (AST, P = 0.0056) and alanine aminotransferase (ALT, P = 0.024). Serum visfatin levels strongly decreased after HP-EVOO ingestion (P = 0.0021). CONCLUSIONS: Daily consumption of polyphenol-rich EVOO might improve metabolic control and circulating inflammatory adipokines profile in overweight T2D patients.

A new species of Silvinichthys (Siluriformes, Trichomycteridae) lacking pelvic fins from mid-elevation localities of the southern Andes, with comments on the genus.

Silvinichthys huachi new species, is described from a stream along the lower slope of the Andean Cordillera in the Provincia de San Juan, Argentina. It shares the distinctive modifications characteristic of Silvinichthys, but is distinguished from the four previously described congeners by the combination of a lack of the pelvic fin and the pelvic girdle, details of pigmentation and various meristic and morphometric features. Silvinichthys huachi is apparently endemic to the type locality situated within an arid region of western central Argentina in the Andino Cuyana Province. Major gaps in the range of species of Silvinichthys may indicate that the origin of the genus predates the uplift events that subdivided drainages along the eastern slopes of the Andean Cordillera in west central Argentina. Silvinichthys huachi is hypothesized to be the sister species of Silvinichthys bortayro.

Acute and long-term effects of low-density lipoprotein (LDL)-apheresis on oxidative damage to LDL and reducing capacity of erythrocytes in patients with severe familial hypercholesterolaemia.

Several studies have suggested that the oxidative modification of low-density lipoprotein (LDL) could play a key role in the early stages of atherosclerosis. The susceptibility of LDL to oxidation has been found to be greater in patients with coronary heart disease. Familial hypercholesterolaemia (FH) is a powerful clinical model in which to study the predictive role of LDL in atherogenesis. LDL-apheresis is a treatment that is able to decrease lipid levels in plasma. This study was aimed at investigating the reducing capacity of erythrocytes and the in vitro susceptibility to oxidation of LDL isolated from patients with homozygous, heterozygous and double-heterozygous FH, who were treated fortnightly with LDL-apheresis or left untreated. In 14 FH patients, at baseline and after a cycle of treatment, the susceptibility of LDL to oxidative modification was analysed by studying the kinetics of conjugate diene formation. Plasma hydroperoxides, polyunsaturated fatty acid content, LDL electrophoretic mobility on agarose, the titre of auto-antibodies against oxidized LDL and serum paraoxonase activity were also measured. Furthermore, in order to evaluate a potential relationship between LDL oxidation and redox status, erythrocyte GSH and ATP levels were determined in FH patients treated regularly or never treated previously by LDL-apheresis. Unlike in the control group, the oxidative status of LDL in all FH patients was modified by LDL-apheresis, as revealed by the higher negative charge and the increase in levels of hydroperoxides and antibodies against oxidized LDL in the plasma. Our findings suggest both an acute effect and a long-term effect of LDL-apheresis in FH patients treated with dextran sulphate cellulose apheresis. The acute effect of LDL-apheresis on the susceptibility to oxidation of plasma and LDL was demonstrated by significant decreases in plasma hydroperoxide content, total LDL concentration and polyunsaturated fatty acid content. The increased resistance of LDL to oxidation was shown by prolongation of the lag time (P<0.05) in samples after a single cycle of treatment. The long-term effect of LDL-apheresis was demonstrated by the comparable values for lag phases (obtained from the kinetics of conjugate diene formation) in patients under active treatment and controls. Compared with healthy controls and untreated patients, the erythrocyte GSH content was significantly higher (P

Redox imbalance and immune functions: opposite effects of oxidized low-density lipoproteins and N-acetylcysteine.

This study investigates the in vitro effects of oxidized low-density lipoproteins (ox-LDL), 'physiological' pro-oxidants, N-acetylcysteine (NAC), a free radical scavenger and glutathione precursor, and their combination on human peripheral blood mononuclear cell functions. We found that treatment with ox-LDL induced a significant down-regulation of proliferative response to mitogens, antigens and interleukin-2. Lipid extracts from ox-LDL were able to reproduce the same effect as the lipoprotein. On the other hand, NAC exposure induced a significant up-regulation of proliferative responses to all the stimuli used. Moreover, we showed that natural killer (NK) cell-mediated cytotoxic activity was significantly down-regulated by ox-LDL while treatment with NAC induced a significant up-regulation of NK-cell activity. Finally, we found that ox-LDL and NAC exerted opposite effects on the cytokine network, interfering both at the protein secretion level and the messenger RNA synthesis level. More importantly, when NAC was used in combination with ox-LDL the proliferative responses, NK-cell-mediated cytotoxic activity and cytokine production were restored to values comparable to controls. These data indicate that ox-LDL and NAC modulate immune functions, exerting opposite effects reflecting their pro-oxidant and antioxidant behaviours. Our results add new insights to the key role played by redox imbalance as a modulator of immune system homeostasis and suggest that an antioxidant drug such as NAC could be useful against pathologies associated with an increase in lipid peroxidation.

Effects of dietary virgin olive oil phenols on low density lipoprotein oxidation in hyperlipidemic patients.

The aim of this study was to assess the effects of the dietary intake of extra virgin olive oil on the oxidative susceptibility of low density lipoproteins (LDL) isolated from the plasma of hyperlipidemic patients. Ten patients with combined hyperlipidemia (mean plasma cholesterol 281 mg/dL, triglycerides 283 mg/dL) consumed a low-fat, low-cholesterol diet, with olive oil (20 g/d) as the only added fat, with no drug or vitamin supplementation for 6 wk. Then they were asked to replace the olive oil they usually consumed with extra virgin olive oil for 4 wk. LDL were isolated at the beginning, and after the 4 wk of dietary treatment. LDL susceptibility to CuSO4-mediated oxidation was evaluated by measuring the extent of lipid peroxidation. We also determined fatty acid composition and vitamin E in plasma and LDL and plasma phenolic content. Extra virgin olive oil intake did not affect fatty acid composition of LDL but significantly reduced the copper-induced formation of LDL hydroperoxides and lipoperoxidation end products as well as the depletion of LDL linoleic and arachidonic acid. A significant increase in the lag phase of conjugated diene formation was observed after dietary treatment. These differences are statistically correlated with the increase in plasma phenolic content observed at the end of the treatment with extra virgin olive oil; they are not correlated with LDL fatty acid composition or vitamin E content, which both remained unmodified after the added fat change. This report suggests that the daily intake of extra virgin olive oil in hyperlipidemic patients could reduce the susceptibility of LDL to oxidation, not only because of its high monounsaturated fatty acid content but probably also because of the antioxidative activity of its phenolic compounds.

Endocrine physiology in a patient-centered learning curriculum.

The medical curriculum at the University of North Dakota School of Medicine and Health Sciences has recently been redesigned into a problem-based/traditional hybrid model that utilizes an integrated organ systems-based approach to teach basic and clinical sciences. The number of lecture hours in general has been greatly reduced, and, in particular, lecture hours in physiology have been reduced by 65%. Students learn basic science in small groups led by a faculty facilitator, and students are responsible for a great deal of their own teaching and learning. The curriculum is centered around patient cases and is called patient-centered learning (PCL). The curriculum includes traditional lectures and laboratories supporting faculty-generated learning objectives. Endocrine physiology is taught in year one, utilizing four weeks of patient cases that emphasize normal structure and function of endocrine systems. Endocrine physiology is revisited in year two, which is primarily focused on pathobiology. The PCL curriculum, with emphasis on the endocrine component, is described in detail along with key portions of an endocrine case.

Susceptibility to oxidation of plasma low-density lipoprotein in X-linked adrenoleukodystrophy: effects of simvastatin treatment.

This paper shows for the first time the higher oxidizability of low-density lipoprotein (LDL) in plasma from adrenoleukodystrophy (ALD) patients compared to that of control subjects. LDL oxidation susceptibility was assessed by conjugate diene formation, hydroperoxide and lipoperoxide formation, and electrophoretic mobility. Simvastatin therapy, an HMG-CoA reductase inhibitor, seems to be a protective pharmacological agent against the higher oxidizability of LDL in plasma from ALD patients.

Renal function and Ca(2+) currents after dye-labeling identification of renal sympathetic neurons.

The present study was performed to determine whether renal efferent sympathetic neurons could be identified using a retrograde neuronal tracer without compromising renal function and whether the labeling and identification procedure alters Ca(2+) currents and neuromodulation of those neurons. Renal sympathetic and superior cervical ganglion (SCG) neurons were labeled with the fluorescent retrograde tracer fast blue. Renal function studies made 1 wk after labeling revealed that renal hemodynamics and fluid and electrolyte excretion were similar between the dye-injected (left) kidney and the control (right) kidney under control conditions and after hemorrhage. After volume expansion, urine flow in the dye-injected kidney was slightly, but significantly, less than that of the control kidney, whereas urinary sodium excretion increased by approximately ninefold in both kidneys. Patch-clamp studies of SCG neurons in 10 mM external Ca(2+) revealed that peak currents were not affected by the presence of the dye or a 1-min exposure to ultraviolet (UV) light. Neither maximal norepinephrine-induced Ca(2+) current inhibition nor the sensitivity to norepinephrine was affected by the dye or 1-min UV exposure. Facilitation protocols revealed that G protein modulation of Ca(2+) currents remained intact in dye-labeled UV-exposed neurons. This study demonstrates that a retrograde fluorescent dye technique to identify renal sympathetic neurons does not compromise renal function and the presence of the dye label or UV exposure has no effect on Ca(2+) currents and neuromodulation in these neurons. Isolation of single identified renal sympathetic neurons coupled with patch-clamp techniques represents a tool to investigate the role of individual current systems in the modulation of excitability in these neurons, which play an important role in the control of renal hemodynamics and excretory function and in the pathogenesis of hypertension.

Neuronal cell bodies in paraventricular nucleus affect renal hemodynamics and excretion via the renal nerves.

Several lines of evidence support the existence of an oligosynaptic projection from the paraventricular nucleus of the hypothalamus (PVN) to the kidney in the rat. We sought to provide evidence that this neural pathway is capable of influencing renal function in rats. Bilateral microinjections of bicuculline (Bic; 1 nmol) into the PVN decreased glomerular filtration rate (59%), effective renal plasma flow (71%), urine flow (UV; 57%), and urinary sodium excretion (UNaV; 54%), accompanied by increased mean arterial pressure (17%) and heart rate (17%). These results were not obtained when Bic was injected outside the PVN or when vehicle (0.9% saline) was injected into the PVN. Bilateral renal denervation (5-7 days before the experiments) significantly reduced the renal vasoconstriction, attenuated the antidiuresis, and abolished the antinatriuresis evoked by PVN stimulation. On the other hand, both the antidiuresis and antinatriuresis evoked by PVN stimulation were undiminished after treatment with either of two vasopressin receptor antagonists ([beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Et-Tyr2, Val4,Arg8]vasopressin, a vasopressin V1 receptor antagonist, or [adamantaneacetyl1,O-Et-D-Tyr2,Val4,aminobutyryl6,Arg8, 9]-vasopressin, a V2 receptor antagonist). In renal-denervated rats treated with the same V2 receptor antagonist, PVN stimulation produced highly variable increases in both UV and UNaV, which overall were not statistically different than zero. We conclude that the activation of neurons in PVN evokes 1) renal vasoconstriction accompanied by antinatriuresis, both of which are attributable to the renal nerves, and 2) decreased water excretion, which is mediated by the renal nerves and vasopressin V2 receptors.

Very late cerebral metastasis from malignant melanoma.

The appearance of cerebral metastases of malignant melanoma (MM) more than 10 years after the primary diagnosis is extremely rare. We report the case of a patient with a solitary brain metastasis of MM who came to our observation 11 years after the treatment of the cutaneous lesion. This patient, who up until then had appeared disease free, presented with two episodes of intracranial haemorrhage in a 5-month period. Neuroradiological findings (CT, MRI, angiogram) did not suggest a brain metastasis. The correct diagnosis was reached only after histopathological examination of the surgically removed lesion. On the basis of this experience, we stress the importance of a long-term clinical and radiological follow-up of all patients with MM.

Cleidocranial dysplasia and syringomyelia. Case report.

cleidocranial dysplasia (CCD) is a dysmorphic syndrome characterized by delayed ossification of the cranial sutures, clavicular hypoplasia and dental dysplasia. We recently observed a 24-year old male patient with CCD and associated syringomyelia and Chiari I malformation (CMI). Only three cases with such an association had been described. The role of posterior fossa bone dysplasia in the pathogenesis of CMI and syringomyelia is discussed.

Renal effects of adrenomedullin in the rat.

We investigated the effects of a constant infusion of adrenomedullin (ADM) on renal hemodynamics and fluid electrolyte excretion in the rat. Following baseline measurements, eight rats received an intravenous infusion of 5 micrograms of rat ADM (167 ng/min) for 30 min at 10 microliters/min. Eight additional rats received 0.9% saline at 10 microliters/min instead of ADM. Renal function was measured during this period and for two consecutive 20-min periods following termination of the ADM or vehicle infusion. Mean arterial pressure decreased from a baseline of 113 +/- 3 to 102 +/- 1 mm Hg at 25 min of ADM infusion and returned towards control after the ADM infusion was terminated. This modest hypotensive effect was associated with an increase in heart rate from 366 +/- 10 to 384 +/- 9 bpm, which continued to remain elevated after the ADM infusion was stopped. Urinary sodium excretion increased from 348 +/- 57 to 813 +/- 172 nEq/min during ADM infusion and continued to increase to 1141 +/- 347 nEq/min after the infusion of ADM was terminated. Urinary potassium excretion increased from 1.94 +/- 0.22 to 2.75 +/- 0.24 microEq/min during ADM infusion. Urine flow tended to increase (P = 0.08) from 7.0 +/- 0.5 to 8.1 +/- 0.6 microliters/min during ADM infusion and continued to increase to 9.7 +/- 1.5 microliters/min after the infusion was stopped. Renal plasma flow increased from 3.22 +/- 0.22 to 3.82 +/- 0.20 ml/min/g kidney wt during ADM infusion and continued to increase to 4.14 +/- 0.22 ml/min/g kidney wt after the ADM infusion was stopped. Glomerular filtration rate averaged to 1.11 +/- 0.07 ml/min/g kidney wt during baseline and did not significantly change during or after ADM infusion. These results indicate that a constant infusion of adrenomedullin, at a dose that results in a minimal hypotensive effect increases renal plasma flow and urinary sodium excretion in the rat.

Adrenomedullin: A newly discovered hormone controlling fluid and electrolyte homeostasis.

Neural and humoral mechanisms controlling fluid and electrolyte homeostasis employ a diverse array of physiologic mechanisms that often, when aberrant, are the underlying cause of disease. Behavioral, hormonal, renal, and vascular responses to volume and osmotic challenges must be coordinated to achieve the goal of homeostasis. In recent years, it has become apparent that there exist a number of hormonal factors produced throughout the body that can coordinate these multiple regulatory mechanisms by complementary effects in several tissues. Thus, in addition to their vasoactive properties, recently characterized hormones such as the natriuretic peptides and the endothelins, as well as the better established renin-angiotensin system, exert central nervous, renal, cardiac, and pituitary effects that regulate normal fluid and electrolyte balance. Now a new player, adrenomedullin, has been added to the cast, and the interplay of multiple hormonal factors involved in the physiology and pathophysiology of volume and osmotic status continues to be elucidated.

Recurrent seizures alter renal function and plasma atrial natriuretic peptide levels in rats.

Status epilepticus can lead to impaired renal function, which has been attributed to complications of myoglobinuria. We confirmed changes in renal function in the absence of myoglobinuria by measuring renal hemodynamics, fluid and electrolyte excretions, and plasma levels of renin and atrial natriuretic peptide (ANP) before and after a 30-min period of recurrent generalized seizures in anesthetized, paralyzed rats. Renal plasma flow (RPF), renal blood flow (RBF) and glomerular filtration rate (GFR) decreased by approximately 60% after seizures. In contrast, urinary sodium excretion, urine flow, and plasma ANP levels increased approximately threefold. Urinary potassium excretion and plasma renin levels were unchanged. Renal function is profoundly altered after 30 min of seizures, primarily due to intense renal vasoconstriction precipitating a dramatic reduction in GFR. The concomitant increases in sodium and urine excretion may be mediated by the marked increase in plasma ANP levels. The decreases in GFR and RBF might contribute to the renal failure observed in some patients after status epilepticus.

Evaluation of fifth nerve dysfunction in 136 patients with middle and posterior cranial fossae tumors.

One-hundred thirty-six patients operated on for extra-axial tumors of the posterior and middle cranial fossae were retrospectively evaluated to define the relevance of trigeminal nerve dysfunction and to correlate clinical and surgical observations. The following data are reported: tumor types, presence of specific trigeminal symptoms and signs, mean duration of symptomatology, anatomical relation between tumor and fifth nerve. Trigeminal symptoms were present in 45 subjects (33.08%) with a mean duration of 23.56 months. Frequency of symptoms was different in various oncotypes. Fifth nerve disturbances were the symptom of onset in 18 subjects (13.23%). A tumoral involvement of the nerve was reported at surgery in 73 patients (53.67%) and was defined as contact, compression or infiltration. Postoperatively, 12 patients showed an improvement of fifth nerve disturbances. A statistically significant difference (p < 0.05) was found in: (1) the incidence of symptoms in patients with and in those without anatomical trigeminal involvement: (2) the incidence of signs in the same groups; (3) the incidence of postoperative relief in patients with fifth nerve compression compared to patients with different surgical findings; (4) the incidence of postoperative relief in patients with typical trigeminal neuralgia compared to those with other symptoms.

Congenital unilateral hydronephrosis in a rat model: continuous renal pelvic and bladder pressures.

We investigated a rat model with inbred unilateral congenital hydronephrosis. Simultaneous bladder and renal pelvic pressures were measured during different urinary flows, and during bladder filling and voiding in these congenitally hydronephrotic rats (approximately 45 days old) and normal nonhydronephrotic rats from the same colony. Differential pressures between pelvis and proximal ureter were determined. Upon termination of the experiment the urinary tract was removed and processed for histological examination. Hydronephrotic rats had significantly higher renal pelvic pressures throughout bladder filling at all urinary flow rates than normal rats. These elevated renal pelvic pressures exceeded bladder pressures at high flows (for example bladder pressure at 50% capacity was 8.9 +/- 3.1 cm. water and corresponding pelvic pressure was 20.8 +/- 2.1 [hydronephrosis] versus pelvic pressure 7.4 +/- 1.1 [control]). While pressures in the proximal ureter were higher than in the pelvis in normal rats the hydronephrotic rats showed significantly higher pressures in the pelvis, suggesting that the site of obstruction is the ureteropelvic junction. Histological evaluation of the excised kidneys revealed only minimal tubular changes. This study represents a unique animal model with unilateral hydronephrosis from a partially obstructing ureteropelvic junction. Moreover, the data indicate that partial urinary obstruction and the associated renal pelvic pressures should be defined with reference to bladder fullness and urinary flow rates.

Juxtamedullary microvascular dysfunction during the hyperfiltration stage of diabetes mellitus.

This study was designed to identify and localize defects in renal microvascular function during the hyperfiltration stage of diabetes mellitus. Male Sprague-Dawley rats were injected intravenously with 65 mg/kg streptozotocin (IDDM rats) or vehicle (sham rats). IDDM rats received insulin (3 U.kg-1.day-1) via an osmotic minipump; sham rats received diluent. During the ensuing 2-wk period, blood glucose levels averaged 89 +/- 2 mg/dl in 33 sham rats and 290 +/- 13 mg/dl in 37 IDDM rats. At the end of this period, inulin clearance was elevated in eight IDDM rats (1.43 +/- 0.17 ml.min-1.g kidney wt-1) compared with six sham rats (0.78 +/- 0.05 ml.min-1.g kidney wt-1). The remaining animals served as tissue donors for study of the renal microvasculature using the in vitro blood-perfused juxtamedullary nephron technique. Kidneys from sham and IDDM rats were perfused with homologous blood at a renal arterial pressure of 110 mmHg. Juxtamedullary single-nephron glomerular filtration rate was higher in IDDM rats (41.5 +/- 5.4 nl/min) than in sham rats (25.4 +/- 2.4 nl/min). Afferent arteriolar inside diameter was greater in IDDM rats (34 +/- 2 microns) than in sham rats (22 +/- 1 microns); however, efferent arteriolar diameter did not differ between groups. The afferent arteriolar vasoconstrictor response to norepinephrine (NE) was attenuated in IDDM rats, relative to sham rats, over a wide range of NE concentrations. In contrast, NE evoked similar degrees of efferent vasoconstriction in IDDM and sham rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in glomerular dynamics in congenital, unilateral hydronephrosis.

We have previously shown that rats with congenital, unilateral hydronephrosis exhibit a reduction in GFR that returns to normal when either the renin angiotensin system or thromboxane A2 (TxA2) is blocked. The current study defines the single nephron defect in congenital, unilateral hydronephrosis and evaluates the roles of angiotensin II (Ang II) and TxA2 in this renal derangement. Renal micropuncture experiments were performed on the right kidney of rats from an inbred colony with unilateral right-sided hydronephrosis (HYDRO), or non-affected litter mates (CONTROL). In addition, four separate groups of hydronephrotic animals were treated with either the TxA2 receptor antagonist SQ-29548 (SQ), one of two Ang II receptor antagonists [saralasin (SAR) or DuP-753 (DUP)]; or combined treatment with DuP-753 and SQ-29,548 (S&D). SNGFR was significantly reduced (P < 0.05) in HYDRO compared to CONTROL (17.6 +/- 2.0 vs. 35.9 +/- 3.7 nl/min, respectively). Treatment with SQ-29,548 normalized SNGFR (29.0 +/- 3.0 nl/min), while saralasin and DuP-753 resulted in only a partial recovery of function (25.6 +/- 1.6 and 27.8 +/- 1.4 nl/min, respectively). Combined SQ-29,548 and DuP-753 treatment resulted in full recovery of SNGFR to 32.9 +/- 4.4 nl/min. The glomerular ultrafiltration coefficient (Kf) was reduced (P < 0.05) approximately 45% in HYDRO compared to CONTROL (1.64 +/- .08 vs. 2.84 +/- .22 nl/min/mm Hg, respectively). Kf returned to control levels in SAR, DUP and SQ, and increased above control in S&D (5.58 +/- 1.6 nl/min/mm Hg). There were no differences (P > 0.05) in hydrostatic or oncotic pressures across the glomerular capillary between any of the groups studied. The observation that Kf increases above CONTROL with combined blockade of TxA2 and Ang II suggests that these regulatory hormones decrease Kf via independent mechanisms. These data indicate that the reduction in SNGFR in congenital, unilateral hydronephrosis is a result of a marked fall in Kf that is mediated by both Ang II and TxA2.