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.

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.

Renal nerves and the pathogenesis of angiotensin-induced hypertension.

The present study examined the role of the renal nerves in the development of hypertension produced by chronic infusion of angiotensin II in the conscious rat. The animals were divided into four groups, and a unilateral nephrectomy was performed. The remaining kidney was denervated in two groups, whereas in the other two groups of animals the nerves were left intact. Four days later either angiotensin II (83 ng/min) or saline infusions were begun through subcutaneously implanted osmotic minipumps. The rats were subsequently studied for 14 days. The results indicate that renal denervation significantly attenuated the pressor response to angiotensin II for approximately 6 days. Following this period, there was no difference in blood pressure between the innervated and denervated rats infused with angiotensin II, as both groups attained a hypertensive level of 170 to 180 mm Hg, which was 60 to 70 mm Hg above the blood pressure of the control rats infused with saline. Kidney norepinephrine content was reduced 95% by the denervation procedure and by 40% following infusion of angiotensin II into rats with intact renal nerves. These data demonstrate that, while the renal nerves appear to play a modulatory role in the development of the hypertension, they are not essential for the pathogenesis to occur nor do they determine the final level of hypertension achieved following chronic infusion of angiotensin II in the rat.

Modulation of renin-angiotensin and kallikrein gene expression in experimental hypertension.

Previous studies have shown that chronic low-dose administration of 40 ng/min angiotensin II by osmotic minipump to uninephrectomized rats mimics the temporal hypertensive response and the circulating angiotensin II levels observed in two-kidney, one clip Goldblatt rats. Furthermore, renal tissue angiotensin II contents were higher than the circulating angiotensin II levels, suggesting that circulating angiotensin II induces endogenous intrarenal angiotensin II production. The present study examined the molecular mechanisms by which intrarenal angiotensin II production is modulated in angiotensin II-induced and two-kidney Goldblatt hypertension. Two weeks after clipping, intrarenal renin mRNA levels were elevated threefold in the clipped kidney of Goldblatt rats but were markedly suppressed in the nonclipped kidneys of Goldblatt rats (28% of control values) and in the remaining kidney of uninephrectomized angiotensin II-infused rats (7% of control values). In contrast, there were sustained levels of angiotensinogen mRNA in the kidneys and livers of Goldblatt and angiotensin II-infused rats, indicating differential regulation of the genes of the renin-angiotensin system. Renal kallikrein gene expression was not altered in either of the hypertensive groups 14 days after the induction of hypertension, suggesting the absence of an enhanced counteracting kinin influence.

Renal mechanisms for suppression of renin secretion by atrial natriuretic factor.

The effects of synthetic atrial natriuretic factor on renin secretion were examined in anesthetized dogs with either a single filtering kidney or a single denervated nonfiltering kidney. In dogs with a single filtering kidney (Series 1, n = 6), a priming dose of atrial natriuretic factor (2 micrograms/kg, i.v.) followed by sustained intravenous infusions at doses of 200 and 400 ng/kg/min for 20 minutes each produced striking decrements (p less than 0.05) in renin secretion, from 1083 +/- 322 to 205 +/- 120 and 286 +/- 168 ng of angiotensin I per minute. This fall in renin secretion was associated with significant increases (p less than 0.05) in creatinine clearance, urine flow, sodium excretion, and the filtered load of sodium. Renal blood flow increased only transiently. In dogs with a single denervated nonfiltering kidney (Series 2, n = 6), infusion of atrial natriuretic factor at these doses also produced marked inhibition (p less than 0.05) of renin secretion, from 311 +/- 98 to 72 +/- 22 and 91 +/- 37 ng of angiotensin I per minute. Renal blood flow remained significantly elevated (p less than 0.05) throughout the infusion, in contrast to renal blood flow in Series I. Similar results were obtained in a third series of dogs (n = 6) with a single denervated nonfiltering kidney, during sustained intrarenal arterial infusions of atrial natriuretic factor. These results suggest that an increase in the sodium load delivered to the macula suppression of renin secretion by atrial natriuretic factor is mediated through its interactions with the two intrarenal receptor mechanisms, the renal vascular receptor and the macula densa.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptide during the elevation in blood pressure induced by sodium restriction.

This study examined the effects of dietary sodium restriction combined with unilateral nephrectomy on systolic blood pressure (SBP), heart rate, plasma renin activity (PRA) and immunoreactive atrial natriuretic peptide (iANP) in the conscious rat. SBP and heart rate, measured by photoelectric tail-cuff, were elevated in both one- and two-kidney, sodium-restricted rats compared with one- and two-kidney rats maintained on a normal-sodium intake. In addition, the SBP of one-kidney, low-sodium rats was significantly elevated compared with two-kidney, low-sodium rats on days 10 and 14 postnephrectomy. PRA was significantly elevated two- to threefold in one- and two-kidney, low-sodium rats compared with rats fed the normal-sodium chow. Plasma iANP levels in rats fed the normal-sodium diet averaged 291 +/- 45 and 277 +/- 35 pg/ml in one- and two-kidney rats, respectively. Plasma iANP levels were significantly lower in the one- and two-kidney, low-sodium rats and averaged 165 +/- 15 and 182 +/- 22 pg/ml, respectively. These results indicate that dietary sodium restriction can elevate blood pressure in the rat and that this response can be augmented by unilateral nephrectomy. In addition, the exacerbation of the hypertension by unilateral nephrectomy in sodium-restricted rats is not attributable to differences in PRA or plasma levels of iANP between one- and two-kidney, sodium-restricted rats.

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.

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.

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.

In vivo proximal tubular fluid-to-plasma chloride concentration gradient in the rabbit.

It has been reported that the concentration of chloride in the proximal tubule is greater than that in plasma in several mammalian species. Much of the theory concerning fluid and electrolyte reabsorption in the proximal tubule is based on data taken from in vitro isolated proximal tubules of the rabbit nephron. This study measured in vivo the rabbit proximal tubule fluid-to-ultrafiltrate chloride concentration ratio [(TF/UF)Cl] and its relationship to proximal tubule length as estimated by the tubule fluid-to-plasma inulin concentration ratio [(TF/P)In]. From six rabbits, 19 random proximal tubules were micropunctured and analyzed for inulin and chloride concentrations, the latter being measured by microelectrometric titration. Plasma ultrafiltrate was determined by correcting plasma chloride concentration for protein concentration. The average single nephron filtration rate was 20.2 +/- 0.8 nl/min. The (TF/UF)Cl ratio was 1.10 +/- 0.03, which was significantly different from unity. Furthermore, regression analysis yielded no significant correlation between the (TF/UF(Cl and (TF/P)In ratio. This study demonstrates that a tubule lumen-to-plasma chloride concentration gradient exists in the in vivo proximal tubule of the rabbit that is apparently established early and is not correlated with proximal tubule length.

Renal autoregulation of blood flow and filtration rate in the rabbit.

Electromagnetic flow techniques and inulin clearance were used to determine the autoregulatory capabilities of the rabbit kidney in vivo. Renal blood flow was measured in 13 animals over a renal perfusion pressure range of 40-110 mmHg. Normal renal blood flow averaged 3.2 +/- 0.3 ml.min-1.g kidney-1 and was efficiently autoregulated above a renal artery pressure of 75 mmHg. For every 10 mmHg renal pressure change above 75 mmHg renal blood flow changed only 0.96%. Renal perfusion pressure was reduced from 102 +/- 3 to 74 +/- 2 mmHg in six animals. Over this pressure range glomerular filtration rate was not significantly decreased and averaged 4.2 +/- 0.5 ml/min at high pressure compared to 4.0 +/- 0.5 ml/min at low perfusion pressure. Results show that the rabbit kidney autoregulates renal blood flow and glomerular filtration rate efficiently above 75 mmHg. This range of autoregulation compares well with the autoregulatory range of the dog. The results also show that in the autoregulatory range the rabbit and the rat appear to autoregulate with equal efficiency but that the rabbit kidney begins to autoregulate at a low perfusion pressure than the average of approximately 100 mmHg usually found in the rat.

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.

Renal response to atrial natriuretic factor in conscious dogs with caval constriction.

Constriction of the thoracic inferior vena cava to decrease venous return and atrial filling markedly elevates plasma renin activity (PRA) and plasma aldosterone concentration (PAC) and produces chronic sodium retention and ascites in the dog. Infusion of a synthetic atrial natriuretic factor into conscious dogs with caval constriction and ascites at doses of 175 and 350 ng X kg-1 X min-1 for 30 min each produced striking increases (P less than 0.05) in creatinine clearance, diuresis, and kaliuresis but failed to increase urinary sodium excretion. Infusions of atrial natriuretic factor at these doses into conscious normal dogs, however, produced a striking increase in sodium excretion from 41 +/- 14 and 55 +/- 19 mu eq/min to 150 +/- 58 and 181 +/- 49 mu eq/min (P less than 0.05 for both values). Creatinine clearance and urine flow also increased in these normal dogs, but potassium excretion remained unchanged during the infusion periods. Atrial natriuretic factor produced parallel suppression (P less than 0.05) of the elevated levels of PRA and PAC in the caval dogs but failed to significantly decrease either PRA or PAC in the normal animals. Arterial pressure, heart rate, and PAH clearance were unchanged in both groups of dogs during infusion of atrial natriuretic factor. These results suggest that the pattern of renal electrolyte excretion elicited in response to the acute infusion of atrial natriuretic factor is dependent, at least partially, on the preexisting status of the renal tubules to facilitate sodium reabsorption and potassium excretion. The results also are consistent with the concept that atrial natriuretic factor might function to tonically inhibit the renin-angiotensin-aldosterone system.

Angiotensin or thromboxane receptor antagonism in rats with congenital hydronephrosis.

A technique for the measurement of GFR without collection of urine in rats was experimentally validated and applied to experiments designed to: (1) evaluate the degree of reduction of GFR in rats with congenital, unilateral hydronephrosis; and (2) to determine if the reduction in renal function is mediated by angiotensin II and/or thromboxane A2 mechanisms. Simultaneous measurements of GFR by a constant-infusion technique and the traditional inulin clearance technique in rats with either one or two normal kidneys were highly correlated (r = 0.934; P < 0.001; N = 17). GFR was approximately 24% lower (P < 0.001) in rats with congenital unilateral hydronephrosis than in rats with a normal kidney. The GFR in rats with hydronephrosis infused with a receptor blocker for either angiotensin II or thromboxane A2 was greater than the GFR in hydronephrotic kidneys without blockade and was not significantly different (P > 0.05) from that in rats with normal kidneys. These results indicate that a constant inulin infusion technique without urine collections can be used to accurately measure GFR in congenitally hydronephrotic kidneys, rendering values free from possible residual pelvic volume artifact. In addition, these results also indicate that a significant 24% reduction in GFR occurs in congenital unilateral hydronephrosis and is mediated by angiotensin II and thromboxane A2 mechanisms.

Trigeminal involvement in intracranial tumours. Anatomical and clinical observations on 73 patients.

Neoplastic involvement of the trigeminal nerve was observed in 73 patients operated on in our institution for extra-axial tumours of the posterior and middle cranial fossae. It was defined as contact, compression, or infiltration. The nerve root was involved in 58 patients, the ganglion and/or the peripheral divisions in 9, all portions of the Vth nerve system in 6. A clinical trigeminal dysfunction was present in 44 patients (60%). Anatomico-surgical findings are correlated with clinical features and with tumour type. Typical trigeminal neuralgia was the complaint in 7 subjects; all of them presented an involvement of the sensory root. Post-operatively, 11 patients were relieved of their symptoms. The outcome is correlated with the anatomical findings and with the extent of surgical removal of the tumours. The importance of a careful evaluation of patients with trigeminal symptomatology is stressed.

Reversible vasoconstriction in rats with congenital unilateral hydronephrosis.

We studied the effects of inhibition of either prostaglandins or the role of prostanoids and the renin-angiotensin system on renal function in rats with congenital unilateral hydronephrosis. Wistar rats with congenital unilateral hydronephrosis were infused with normal saline (control), captopril dissolved in normal saline or indomethacin dissolved in a solution of sodium chloride and sodium carbonate. In the control group both glomerular filtration rate (GFR) and effective renal plasma flow were reduced in the right hydronephrotic kidney (RHK) compared with the normal left kidney. Indomethacin did not improve renal function in the RHK. Captopril significantly improved GFR in the RHK. These results support the conclusion that the renin-angiotensin system is an important mediator of reduced GFR in congenital unilateral hydronephrosis in rats.

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.

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.