Pharmacologycal activity of peperina (Minthostachys verticillata) on gastrointestinal tract.

ETHNOPHARMACOLOGICAL RELEVANCE: Minthostachys verticillata (Griseb.) Epling (Lamiaceae), known as Peperina is a medicinal native plant, with a traditional use as a digestive, antispasmodic and antidiarrheic. AIM OF THE STUDY: Despite its folkloric use, no scientific evaluation of this plant related to the gastrointestinal inflammatory process has been carried out to date. The present study aims to assess the effects of M. verticillata on gastrointestinal system in experimental models. MATERIALS AND METHODS: M. verticillata (250 and 500 mg/kg) was orally tested in a colitis model induced by acetic acid. Colon weight/length ratio, oxidative stress (oxidized and reduced glutathione), histological changes using Alcian blue and hematoxylin & eosin staining and expression of IL1ß, TNFα, iNOS, COX-2 were evaluated. The effect of the extract in three additional in vivo models were studied: intestinal motility and diarrhea induced by ricin oil, and visceral pain induced by intracolonic administration of capsaicin. Finally, the activity on concentration response curves of acetylcholine, calcium chloride, potassium and serotonin were achieved in isolated rat jejunum. RESULTS: In the colitis model, M. verticillata induced a significant reduction in the colon weight/length ratio, oxidative stress and expression levels of IL-1ß, iNOS and COX-2. Also, the extract diminished the severity of microscopic tissue damage and showed protective effect on goblet cells. Intestinal motility, diarrhea, visceral pain-related behaviors and referred hyperalgesia were significantly reduced when the animals were treated with the extract. Furthermore, in isolated jejunum, M. verticillata significantly reduced the contraction induced by serotonin and acetylcholine. Likewise, the extract non-competitively inhibited the response-concentration induced by CaCl2 and inhibited both low and high K+-induced contractions. CONCLUSIONS: This is the first study to validate traditional use of M. verticillata for digestive disorders and demonstrated that its aqueous extract could represent a promising strategy in targeting the multifactorial pathophysiology of inflammatory bowel disease.

Beneficial properties of Passiflora caerulea on experimental colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Passiflora caerulea L. (Passifloraceae) is a medicinal plant commonly used in traditional medicine in South America for different pathologies associated with the gastrointestinal tract. AIM OF THE STUDY: In the present study, the activity of the ethanolic extract of P. caerulea on an experimental colitis model related to inflammatory bowel disease has been investigated. MATERIALS AND METHODS: Colitis was induced by intracolonic instillation of a 2mL of 4% (v/v) acetic acid solution. Macroscopic scoring, myeloperoxidase activity and thiobarbituric acid reactive substances levels were evaluated on isolated colon mucosae. The histopathological studies of colon mucosae were performed by hematoxylin and eosin and Alcian blue staining. Diarrhoea was induced by the administration of castor oil (0.3mL/mouse). The first watery defecation time, the total amount of solid, semi-solid and watery stools and the amount of watery stools were determined. The effect of the extract on a cumulative concentration-response curve of acetylcholine and CaCl2 on isolated rat jejunum was also evaluated. The phytochemical analysis was performed. RESULTS: The extract (250mg/kg, p.o.) induced a significant reduction in the weight/length ratio, the macroscopic lesion score, TBARS levels and the microscopic tissue damage when compared with the acetic acid-treated group of animals. P. caerulea (125mg/kg, p.o.) decreased significantly the amount of watery stools in the castor oil-induced-diarrhoea model. Moreover, the P. caerulea extract antagonized the jejunum contractions induced by Ach (Emax for 0.3mg/mL: 76.25%; Emax for 1mg/mL: 63.47%; Emax for 3mg/mL: 42.01%) and CaCl2 (Emax for 0.3mg/mL: 75.69%; Emax for1 mg/mL: 56.1%; Emax for 3mg/mL: 53.4%). Isoorientin, vitexin, isovitexin, and vicenin-2 were identified in the extract. CONCLUSION: P. caerulea showed anti-inflammatory, anti-diarrhoeal and spasmolityc activities on preclinical models.

Anti-inflammatory and antinociceptive activity of Urera aurantiaca.

Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti-inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti-inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan-induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose-dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis 3-ethylbenzothiazoline 6-sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED50 : 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity.

Tempol-nebivolol therapy potentiates hypotensive effect increasing NO bioavailability and signaling pathway.

Nebivolol is a third generation beta blocker with endothelial nitric oxide synthase (eNOS) agonist properties. Considering the role of reactive oxygen species (ROS) in the uncoupling of eNOS, we hypothesized that the preadministration of an antioxidant as tempol, could improve the hypotensive response of nebivolol in normotensive animals increasing the nitric oxide (NO) bioavailability by a reduction of superoxide (O2(•-)) basal level production in the vascular tissue. Male Sprague Dawley rats were given tap water to drink (control group) or tempol (an antioxidant scavenger of superoxide) for 1 week. After 1 week, Nebivolol, at a dose of 3 mg/kg, was injected intravenously to the control group or to the tempol-treated group. Mean arterial pressure, heart rate, and blood pressure variability were evaluated in the control, tempol, nebivolol, and tempol nebivolol groups, as well as, the effect of different inhibitor as Nß-nitro-l-arginine methyl ester (L-NAME, a Nitric oxide synthase blocker) or glybenclamide, a KATP channel inhibitor. Also, the expression of α,ß soluble guanylate cyclase (sGC), phospho-eNOS, and phospho-vasodilator-stimulated phosphoprotein (P-VASP) were evaluated by Western Blot and cyclic guanosine monophosphate (cGMP) levels by an enzyme-linked immunosorbent assay (ELISA) commercial kit assay. We showed that pretreatment with tempol in normotensive rats produces a hypotensive response after nebivolol administration through an increase in the NO bioavailability and sGC, improving the NO/cGMP/protein kinase G (PKG) pathway compared to that of the nebivolol group. We demonstrated that tempol preadministration beneficiates the response of a third-generation beta blocker with eNOS stimulation properties, decreasing the basal uncoupling of eNOS, and improving NO bioavailability. Our results clearly open a possible new strategy therapeutic for treating hypertension.

Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis.

ETHNOPHARMACOLOGICAL RELEVANCE: Urtica circularis (Hicken) Sorarú is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. AIM OF THE STUDY: In the present study, the in vivo antinociceptive effect of Urtica circularis ethanolic extract and its isolated compounds has been investigated. MATERIALS AND METHODS: Antinociceptive activity was evaluated through writhing, formalin and hot plate tests in mice. The phytochemical analysis was performed. RESULTS: The extract produced significant inhibition on nociception induced by acetic acid (ED50: 72.2mg/kg, i.p.) and formalin (ED50: 15.8 mg/kg, i.p.) administered intraperitoneally and also orally. Atropine diminished the activity of the extract in the acetic acid test. In this model, at dose of 10mg/kg i.p., vitexin was the most active of the isolated compounds (inhibition of 91%), and chlorogenic acid, caffeic acid and vicenin-2 (6,8-di-C-glucosyl apigenin) produced an inhibition of 72%, 41% and 41%, respectively, whereas apigenin did not show any activity. CONCLUSIONS: These results suggest that Urtica circularis extract produced antinociception possibly related to the presence of vitexin, chlorogenic, caffeic acid and vicenin-2. The activation of cholinergic systems seems to be involved in the mechanism of antinociception of the extract.

Anti-inflammatory effect of Lithrea molleoides extracts and isolated active compounds.

AIM OF THE STUDY: In this study the anti-inflammatory activity of aqueous, dichloromethane (CH2Cl2) and methanolic (MeOH) extracts and two major compounds isolated from Lithrea molleoides (Vell.) Engl. (Anacardiaceae) were evaluated. MATERIALS AND METHODS: Two classical experimental models were used, carrageenan-induced rat paw edema and 12-O-tetradecanoylphorbol-13 acetate (TPA) induced mouse ear edema. RESULTS: MeOH extracts exhibited a significant systemical anti-inflammatory effect in the carrageenan (inhibition of 46% at 3 h) and in the TPA-ear edema test (inhibition of 21%). The presence of methyl gallate (inhibition of 63% in TPA ear edema), as one of the main compounds in the active fraction from MeOH extract may be explained the effect observed. Also, 1,3-dihydroxy-(Z,Z)-5-(tridec-4',7́dienyl) benzene obtained from CH2Cl2 extract showed a significant topical anti-inflammatory activity (inhibition of 68%). Furthermore, no signs of toxicity were observed with doses up to 3g/kg in an acute toxicity assay. CONCLUSIONS: The results of this study present evidence that Lithrea molleoides given either systemically or topically has anti-inflammatory properties.

Prevalence of ergot derivatives in natural ryegrass pastures: detection and pathogenicity in the horse.

In the present study, we determined the incidence and effects of season and weather on clinical manifestations of endophyte-infected ryegrass toxicity, performed chemical detection and pharmacological bioassays on ryegrass extracts, and conducted trials on: (i) effects of domperidone or metochlopramide on ovarian inactivity induced by endophyte-infected ryegrass; (ii) efficacy of buspirone or dihydrochloro phenyl piperazine (m-CPP) for preventing suppressed milk production induced by endophyte-infected ryegrass; and (iii) efficacy of domperidone to induce ovulation during winter anestrus. Mares with toxicosis had prolonged gestation, embryonic losses, dystocia, poor mammary gland development, low milk production, prolonged uterine involution, and suppressed ovarian activity. Foals had respiratory failure, abnormalities of the skin, umbilicus, bone, and muscle, failure to thrive, blindness, testicular atrophy, and decreased serum total immunoglobulin concentrations. Endophyte-infected ryegrass and the incidence of toxicosis were correlated (r=0.861, P=0.03). Ergot alkaloids were not detected in extracts of endophyte-infected ryegrass by either thin-layer chromatography or spectrophotometry, but their presence was inferred in bioassays of extracts (dose-related increases in the contractile response of rat uterus). Mares given metoclopropamide (0.6 mg/kg/d), given orally every 8h for up to 7d) ovulated earlier (4-7d vs. 15-18d, P<0.001) than those given domperidone (1.1mg/kg/d) orally for up to 18d). Although both metoclopropamide and domperidone induced milk production, the latter did not induce ovarian cyclicity in healthy mares during seasonal anestrus. Based on these findings, we inferred that endophyte-infected ryegrass is associated with ergot alkaloid intoxication in horse.

Anti-inflammatory activity of flavonoids from Eupatorium arnottianum.

Three anti-inflammatory compounds: nepetin, jaceosidin and hispidulin have been isolated and identified from Eupatorium arnottianum Griseb. dichloromethane extract. Nepetin reduced the TPA mouse ear edema by 46.9% and jaceosidin by 23.2% (1mg/ear). Both compounds inhibited the NF kappaB induction by 91 and 77%, respectively. Furthermore phytochemical analysis of the ethanol extract has led to the identification of eriodictyol, hyperoside, rutin, caffeic and chlorogenic acids. All these compounds are reported for the first time in this species. The finding of topical antiinflammatory activity exerted by Eupatorium arnottianum extract and the identification of active principles could support the use of this plant for the treatment of inflammatory affections.

Acute sodium overload produces renal tubulointerstitial inflammation in normal rats.

The aim of the present study was to determine whether acute sodium overload could trigger an inflammatory reaction in the tubulointerstitial (TI) compartment in normal rats. Four groups of Sprague-Dawley rats received increasing NaCl concentrations by intravenous infusion. Control (C): Na+ 0.15 M; G1: Na+ 0.5 M; G2: Na+ 1.0 M; and G3: Na+ 1.5 M. Creatinine clearance, mean arterial pressure (MAP), renal blood flow (RBF), and sodium fractional excretion were determined. Transforming growth factor beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), RANTES, transcription factor nuclear factor-kappa B (NF-kappaB), and angiotensin II (ANG II) were evaluated in kidneys by immunohistochemistry. Animals with NaCl overload showed normal glomerular function without MAP and RBF modifications and exhibited a concentration-dependent natriuretic response. Plasmatic sodium increased in G2 (P < 0.01) and G3 (P < 0.001). Light microscopy did not show renal morphological damage. Immunohistochemistry revealed an increased number of ANG II-positive tubular cells in G2 and G3, and positive immunostaining for NF-kappaB only in G3 (P < 0.01). Increased staining of alpha-SMA in the interstitium (P < 0.01), TGF-beta1 in tubular cells (P < 0.01), and a significant percentage (P < 0.01) of positive immunostaining for RANTES in tubular epithelium and in glomerular and peritubular endothelium were detected in G3 > G2 > C group. These results suggest that an acute sodium overload is able 'per se' to initiate TI endothelial inflammatory reaction (glomerular and peritubular) and incipient fibrosis in normal rats, independently of hemodynamic modifications. Furthermore, these findings are consistent with the possibility that activation of NF-kappaB and local ANG II may be involved in the pathway of this inflammatory process.

Antinociceptive and antiinflammatory activities of Artemisia copa extracts.

The aqueous extract from aerial parts of Artemisia copa Phil. (Compositae), was evaluated for antinociceptive activity using writhing, formalin, and hot-plate tests in mice. A dose-related antinociceptive response was obtained in the writhing test at doses of 500 and 1000 mg/kg p.o. (percentage of inhibition 23.3 and 52.70, respectively). The extract also inhibited the second phase of formalin test (38.81%) and this effect was not antagonized by pretreatment with naloxone 5mg/kg i.p. Furthermore, no significant effect was obtained in the hot-plate test. Dichloromethane and ethanolic extracts, were analyzed for antiinflammatory activity with the carrageenan-induced paw edema in rats and the ear edema induced by 12-O-tetradecanoylphorbol-13 acetate (TPA) and arachidonic acid (AA) in mice. Both extracts showed antiinflammatory activity in the TPA (88 and 54%), and the ethanolic extract showed a 37% inhibition in AA test. No effects were seen at doses of 300 mg/kg p.o. and 100 mg/kg i.p. in the carrageenan test. The results obtained indicate that A. copa has analgesic and topical antiinflammatory activities that supports the folk medicinal use of the plant.

Hepatoprotective activity of Achyrocline satureioides(Lam) D. C.

Aerial parts of Achyrocline satureioides(Lam) D. C. (Asteraceae) are used in folk medicine as infusions or decoctions for the management of several diseases including gastrointestinal and hepatic disorders. These data and the presence of flavonoids and caffeoyl derivatives have led us to study its hepatoprotective and choleretic activities. The hepatoprotective activity was evaluated in the bromobenzene- (BB-) induced hepatotoxicity model in mice through the measurement of the serum levels of alanine-aminotransferase (ALT) and aspartate transaminase (AST), thiobarbituric acid reacting substances (TBARS) and glutathione levels. The aqueous extract of the aerial parts of A. satureioides administered before BB, at the dose of 300 mg kg(-1)p.o., demonstrated significant inhibition (P< 0.01) in the BB increase of liver ALT and AST and in the BB-induced increase of liver TBARS content. Also it was able to significantly increase (P< 0.05) the depleted levels of liver glutathione. In addition, at the same dose, a significant increase (P< 0.01) in the bile flow of rats was found. The results obtained with the aqueous extract of A. satureioides support its use in popular medicine as a hepatoprotective and digestive agent, and the effects might be mediated through the antioxidant and choleretic activities.

Phenolic compounds with anti-inflammatory activity from Eupatorium buniifolium.

Anti-inflammatory activity was detected in the CH(2)Cl(2) extract of the aerial parts of Eupatorium buniifolium using the TPA-mouse ear model. Three compounds isolated from this extract, by bioassay-guided fractionation, significantly inhibited the inflammatory response. The compounds were identified as 5,7,5'-trihydroxy-3,6,2',4'-tetramethoxyflavone (1), scopoletin (2) and centaureidin (3) which inhibited the edema by 67.3 %, 59.8 % and 49.7 %, respectively, at a dose of 1 mg/ear.

Pharmacokinetic and pharmacodynamic alterations of methyldopa in rats with aortic coarctation. A study using microdialysis.

A pharmacokinetic-pharmacodynamic study of methyldopa (MD) was made in anesthetized sham operated (SO) and aortic coarctated (ACo) rats by using a vascular shunt probe for arterial microdialysis and simultaneous blood pressure recording. Anesthetized Wistar rats were used 7 days after aortic coarctation or sham operation. A vascular shunt probe was inserted into the carotid artery and a concentric probe was placed into the striatum or posterior hypothalamus. MD and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the dialysates by HPLC-EC. MD (50 mg kg(-1)i.p.) induced an increase of heart rate in SO (Delta HR: 108 +/- 22 bpm, n= 6) and in ACo rats (Delta HR: 55 +/- 10 bpm, n= 6, P< 0.05, one way ANOVA). Moreover, MD also reduced the mean arterial pressure (MAP) of SO rats (Delta MAP: -10 +/- 4 mmHg, n= 6) and ACo animals (Delta MAP: -51 +/- 9 mmHg, n= 6, P< 0.05, one way ANOVA). Analysis of the arterial blood dialysates showed a lower half-life of MD in ACo rats (t(1/2): 1.5 +/- 0.3 h, n= 6, P< 0.05, 't' test) than in SO rats (t(1/2): 3.7 +/- 1.0 h, n= 6). A low accumulation and a fast decay of striatal MD levels were seen in ACo rats. However, peak levels of drug were greater in the hypothalamic dialysates of ACo rats than in SO animals samples. On the other hand, MD also induced an increase of DOPAC levels in the hypothalamic dialysates of ACo rats. In conclusion, the aortic coarctation modifies the pharmacokinetic and cardiovascular effect of MD in the rat. The action of this drug on dopaminergic neurotransmission is also altered in the ACo animals.

Choleretic effect and intestinal propulsion of 'mate' (Ilex paraguariensis) and its substitutes or adulterants.

'Mate' or 'Yerba mate' (Ilex paraguariensis, Aquifoliaceae) is a tonic and stimulant beverage widely used in South America. It is also traditionally used in gastrointestinal disorders as eupeptic and choleretic agent. Accordingly, the effect of decoctions of the leaves of I. paraguariensis and three of its substitutes or adulterants (Ilex brevicuspis, Ilex argentina and Ilex theezans) on bile flow (BF) and intestinal propulsion were investigated. I. paraguariensis and I. brevicuspis induced an increase in BF, while the latter also enhanced intestinal transit. In contrast, neither I. argentina nor I. theezans exerted any effect on BF or intestinal propulsion. These results suggest that the therapeutic properties of I. paraguariensis will be affected when at least an adulterant is present in the final commercial product of Yerba mate.

Antinociceptive effect of some Argentine medicinal species of Eupatorium.

Eupatorium laevigatum, E. arnottianum and E. subhastatum, plants used in Argentine folk medicine for the treatment of inflammation and pain related problems, were evaluated for analgesic activity. The infusions of these species (500 mg/kg, p.o.) produced a reduction in the number of stretches of 46.6%, 41.5% and 35.6% respectively, in the acetic acid induced writhing test. This antinociceptive effect of the infusions was not reversed by pretreatment with naloxone. The infusions studied did not produce antinociceptive effects when assayed in the hot plate test. These results suggest that the analgesic activity is exerted by a mechanism unrelated to interaction with opioid systems.

Diuretic activity of an aqueous extract of Phyllanthus sellowianus.

Phyllanthus sellowianus Muell. Arg. (Euphorbiaceae) is used widely as a hypoglycemic and diuretic agent in South American folk medicine. In order to assess the diuretic activity of this plant, test animals were treated with a single oral administration of an aqueous extract (5% w/v) of the stem bark of P. sellowianus (400 mg/kg body weight), which produced after 8 h a significant increase in the urinary excretion. In the studies on acute toxicity in mice neither mortality nor neurobehavioral or autonomic profile changes could be observed.

[Effect of treatment with dexamethasone on cardiovascular responses of adrenergic agents]. / Efecto del tratamiento con dexametasona sobre las respuestas cardiovasculares de agentes adrenérgicos.

Cardiovascular responses to several agents should be modified by glucocorticoid administration in the rat. We investigate the response to adrenergic agonists such as phenylephrine, noradrenaline, clonidine and isoproterenol and ganglionic blocking agent such as hexamethonium in conscious rats treated during 7 days with dexamethasone. Wistar rats were treated with either Dex (150 micrograms daily x 7 days, p.o.) or water. Mean arterial pressure were calculated from the intraarterial recordings of blood pressure. No differences in basal mean arterial pressure were seen between dexamethasone and control groups of rats. Phenylephrine and noradrenaline showed a pressor effect in control rats that was reduced by dexamethasone treatment. Clonidine showed similar pressor effect in both groups of rats but ten minutes after drug administration, a light hypotension was seen in dexamethasone rats. Isoproterenol and hexamethonium showed a similar hypotensive effect on control and dexamethasone rats. In conclusion, dexamethasone treatment should reduce the pressor responses to phenylephrine and noradrenaline. Moreover, the alpha adrenergic agonist clonidine showed a hypotensive effect in dexamethasone treated rats, although the response of isoproterenol and hexamethonium remains unchanged.

Antidiabetic activity of Phyllanthus sellowianus in streptozotocin-induced diabetic rats.

The aqueous extract (5% w/v) of the stem barks of Phyllanthus sellowianus Müller Arg. (Euphorbiaceae) was administered orally at the dose of 4 ml/100 g body weight (corresponding to 2 g of dry plant material/kg body weight) to normal and streptozotocin-induced diabetic rats. Blood glucose was estimated 3 weeks after daily administration of the extract and was compared to the pre-treatment level. The results show that the administration of the extract significantly lowered the blood glucose in the diabetic rats.

Search for antiinflammatory activity in Argentine Medicinal Plants.

Extracts of different polarity from four Argentine medicinal plants used in folk medicine as antiinflammatory remedies were tested for bioactivity using carrageenan-induced paw edema in rats and TPA-induced ear edema in mice. A dichloromethane extract from Pluchea sagittalis showed good antiinflammatory activity in both tests. Flavonoids present in this extract may be responsible for the activity. Ipomoea fistulosa dichloromethane extract showed significant activity in the ear edema test while a dichloromethane extract from Eupatorium inulaefolium and aqueous extract of Polygonum punctatum exhibited antiinflammatory activity in the carrageenan-induced edema test.

Renal function conscious one kidney-one clip hypertensive rats. Effect of indomethacin.

These experiments have analyzed: a) Blood pressure (BP) and renal function in one kidney-one clip rats two weeks after clipping; b) The effect of cycloxygenase (CO) inhibition on BP and renal function regulation during the hypertensive period. Using the unanaesthetized, unrestrained and chronically instrumented animal, three groups of rats were studied: Sham, Clip 0.31 mm lumen and Clip 0.29 mm lumen. The animals were examined before (Control period) and during the infusion of indomethacin (IND, 5 mg/kg via aortic cannula, n = 11 for each group) or the buffer vehicle solution (BUF, n = 7 for each group). Effective inhibition of CO by IND was confirmed using radioimmunoassay of prostaglandin E2 (PGE2) in urine. Control BP (mmHg, mean +/- SE) differed significantly among the groups (p < 0.001): Sham, 114 +/- 3; Clip 0.31, 135 +/- 2; Clip 0.29, 154 +/- 4 and did not change by IND infusion. Along with the BP, Control Glomerular Filtration Rate and Renal Plasma Flow did not change by IND infusion, which suggests that CO eicosanoids, particularly PGG2, contribute little to basal renal hemodynamics in sham and hypertensive rats. Sodium excretion was lower in the Control period of Clip 0.29 rats (p < 0.01). A significant natriuretic effect observed in this Clip 0.29 group by the infusion of IND suggests the contribution of an AA related metabolite in renal handling of sodium in more severe renovascular hypertension.