The adipose tissue and the involvement of the renin-angiotensin-aldosterone system in cardiometabolic syndrome.

Cardiometabolic diseases are linked to a cluster of modifiable factors, including risk factors closely related to central adiposity. Chronic renin-angiotensin-aldosterone system (RAAS) activation has far-reaching effects on cardiometabolic risk and is a substantial contributor to this clinical condition. RAAS components are locally expressed in the vessels and adipose tissue. This review appoints RAAS, through the classical and the alternative view, as the main mediator of the cross-talk in cardiometabolic syndrome.

Salivary cortisol concentrations, stress and quality of life in women with endometriosis and chronic pelvic pain.

The objective of this study was to evaluate the perceived stress index, quality of life, and hypothalamus-pituitary-adrenal axis activity in women with endometriosis and chronic pelvic pain. For the study, 93 women with endometriosis and 82 healthy women volunteered. The visual analogue scale (VAS) (0=no pain; 10=severe pain) was used to determine pain intensity; the perceived stress questionnaire (PSQ) defined stress index, and the health-related quality-of-life (HRQOL)-SF-36 questionnaire was used to evaluate quality of life. Salivary cortisol was measured at 0800, 1600, and 2000 h and the awakening cortisol response was assessed to evaluate the hypothalamus-pituitary-adrenal axis activity. The results show that women with endometriosis and chronic pelvic pain of moderate intensity (4.1+/-0.58, mean+/-SEM) have higher levels of perceived stress (0.55+/-0.01 versus 0.42+/-0.01, p<0.05), a poorer quality of life expressed as lower scores for all items of the inventory and hypocortisolism. Lower levels of salivary cortisol were observed in all three samples collected, as well as in the awakening cortisol response, for women with endometriosis (0.19+/-0.09 microg/dl) when compared with controls (0.78+/-0.08 microg/dl, p<0.05 l), and it was independent of pain intensity and Mental health (MH) scores in SF-36. We concluded that women with endometriosis and chronic pelvic pain show low concentrations of salivary cortisol and a high level of perceived stress, associated with a poor quality of life. Whether the hypocortisolism was an adaptive response to the aversive symptoms of the disorder or a feature related to the etiology of endometriosis remains to be elucidated.

Overexpression of apolipoprotein CIII increases and CETP reverses diet-induced obesity in transgenic mice.

OBJECTIVE: We recently described that hypertriglyceridemic apolipoprotein (apo) CIII transgenic mice show increased whole body metabolic rate. In this study, we used these apo CIII-expressing mice, combined or not with the expression of the natural promoter-driven CETP gene, to test the hypothesis that both proteins modulate diet-induced obesity. MEASUREMENTS AND RESULTS: Mice expressing apo CIII, CIII/CETP, CETP and nontransgenic (NonTg) mice were maintained on a high-fat diet (14% fat by weight) during 20 weeks after weaning. At the end of this period, all groups exhibited the expected lipemic phenotype. Fasting glucose levels were neither affected by the high-fat diet nor by the distinct genotypes. However, apo CIII mice showed significantly higher glycemia ( approximately 35%) and lower insulin levels ( approximately 45%) in the fed state, compared with the NonTg mice. The apo CIII mice presented significantly increased body weight, lipid content of the carcass ( approximately 25%), visceral adipose tissue mass (about twofold) and adipocyte size ( approximately 25%) compared with the CETP and NonTg mice. The CETP expression in the apo CIII background normalized the subcutaneous adipose depot and visceral adipocyte size to the levels of NonTg mice. Plasma leptin levels were lower in CETP groups (25-50%) and higher in the apo CIII mice. Similar core body temperature in all groups and similar liver mitochondrial resting respiration rates in CIII and NonTg mice indicate no differences in basal energy expenditure rates among these mice fed a high-fat diet. CONCLUSION: The elevation of plasma apo CIII levels aggravates diet-induced obesity and the expression of physiological levels of circulating CETP reverses this adipogenic effect, indicating a novel role for CETP in modulating adiposity.

The effects of ruthenium tetraammine compounds on vascular smooth muscle.

The time course of the relaxation effect induced by a single dose (3 x 10(-6) mol/L) of trans-[Ru(NH3)4L(NO)]3+ (L=nic, 4-pic, py, imN, P(OEt)3, SO(3)(2-), NH3, and pz) species and sodium nitroprusside (4 x 10(-9) mol/L) was studied in aortic rings without endothelium and pre-contracted with noradrenaline (1 x 10(-6) mol/L). All the compounds induced a relaxing effect in the aortic rings, but the intensity and time of relaxation were different. Only the species where L=py, 4-pic, and P(OEt)3 were able to induce 100% (99-100%) of the relaxing effect during the assay. trans-[Ru(NH3)4(L)(NO)]3+ (L=SO(3)(2-) and NH3) showed the lowest relaxing effect (36 and 37%, respectively) when compared with the other compounds. Relationship was observed between the time corresponding to half of the maximum relaxation intensity observed and, respectively, k-NO, E0'[Ru(NO)]3+/[Ru(NO)]2+ in trans-[Ru(NH3)4(L)(NO)]3+ species and E0'Ru(III)/Ru(II) in trans-[Ru(NH3)4(L)(H2O)]3+ ions. These relationships strongly suggested that the NO liberation from the reduced nitrosyl complexes was responsible for the observed relaxation.

Effect of swimming session duration and repetition on metabolic markers in rats.

The aim of this study was to investigate the profile of metabolites in male rats subjected to 50-60 min of swimming on three protocols: group A, a single 50 min swimming session; group B, one session a day for three days (5 min on day 1, 15 min on day 2 and 30 min on day 3); and group C, one session a day for 5 days, with increasing duration from 5 min on day 1, 15, 30, 45 and 60 min on consecutive days. The interval between sessions was 24 h. Measurements were made after the last swimming session. Controls did not swim. The glycogen content of liver and gastrocnemius and soleus muscle was depleted in the three groups that swam, but blood glucose concentration was significantly increased only in group B. Serum lactate concentrations were greater than the controls in groups A and B. There were significant increases in serum free fatty acid concentrations in all groups that swam. The increases in plasma free fatty acids may have resulted from lipolysis stimulated by endogenous catecholamines in groups A and C, since basal lipolysis measured in vitro was unchanged by swimming. The large increase in basal lipolysis in group B may have contributed to the rise in plasma free fatty acids. Adipocytes from rats in groups A and B were supersensitive to epinephrine, whereas those from group C were not. We conclude that the metabolic alterations were less pronounced after the last of five swimming sessions over 5 days than after a single session, even though session duration and the contribution of the physical component were similar. Glucose mobilization, but probably not utilization, was similar in the three groups that swam. The mechanisms of lipid mobilization from adipose tissue differed, depending on the stress paradigm. The metabolic changes in groups A and B indicated that three daily swimming sessions were insufficient to cause adaptation. The results contrast with previous findings for foot-shock stress, which leads to sensitization rather than adaptation in response to repeated stimuli.

Effect of essential oil obtained from Croton cajucara Benth. on gastric ulcer healing and protective factors of the gastric mucosa.

The bark of Croton cajucara Benth. (Euphorbiaceae) is used widely in Amazonian folk medicine for the treatment of a wide range of gastrointestinal symptoms. Infusions of C. cajucara bark contain dehydrocrotonin (DHC), the furan diterpene, and an essential oil, a rich mixture of sesquiterpenes. Although the antiulcerogenic activity of the essential oil has been studied in different gastric ulcer models in mice and rats, its mechanism remains unclear. In this work, we examined the ability of this essential oil to increase PGE2 release from mucus cells, as well as its effects on the amount of gastric mucus and on the healing of acetic acid-induced gastric ulcers. The essential oil (100 mg/kg body wt., p.o), significantly increased PGE2 production by glandular cells (by 102% as compared to control) and the amount of Alcian blue binding to the gastric mucus. In chronic gastric ulcers, a single daily oral dose of essential oil (100 mg/kg body wt.) for 14 consecutive days accelerated ulcer healing to an extent similar to that seen with an equal dose of cimetidine. Thus, the protective and healing actions of the essential oil from C. cajucara bark on gastric lesions resulted mainly from an increase in PGE2 release and gastric mucus formation which would protect the gastric mucosa.

Metabolic markers following beta-adrenoceptor agonist infusion in footshock-stressed rats

Stress hormones can alter metabolic functions in adipose tissue and liver, as well as the sensitivity of rat white adipocytes and rat atrial responses to ß-adrenergic agonists. In this study, we examined the effects of three daily footshock stress sessions on the plasma corticosterone, glucose, glycerol and triacylglycerol levels of fed, conscious male rats, and on the plasma glucose, glycerol and triacylglycerol levels of the same rats following iv infusions of ß-adrenergic agonists (isoproterenol: 0.4 nmol kg-1 min-1, noradrenaline: 5.0 æg kg-1 day-1, and BRL 37344 ([+ or -]-[4-(2-[(2-[3-chlorophenyl]-2-hydroxyethyl)amino]propyl)phenoxy]acetic acid), a selective ß3-adrenoceptor agonist: 0.4 nmol kg-1 min-1). Plasma corticosterone levels increased significantly after each stress session, while triacylglycerol levels increased after the first session and glucose increased after the second and third sessions. Glycerol levels were unaltered after stress. These results suggest that repeated footshock stress may induce a metabolic shift from triacylglycerol biosynthesis to glucose release by hepatic tissue, with glycerol serving as one of the substrates in both pathways. Stressed rats were more sensitive to infusion of noradrenaline plus prazosin and to infusion of isoproterenol, with elevated plasma glucose, glycerol and triacylglycerol levels. The higher sensitivity of stressed rats to isoproterenol and noradrenaline was probably related to the permissive effect of plasma corticosterone. Only BRL 37344 increased plasma glycerol levels in stressed rats, probably because ß3-adrenoceptors are not involved in hepatic triacylglycerol synthesis, thus allowing glycerol to accumulate in plasma

Metabolic markers following beta-adrenoceptor agonist infusion in footshock-stressed rats.

Stress hormones can alter metabolic functions in adipose tissue and liver, as well as the sensitivity of rat white adipocytes and rat atrial responses to beta-adrenergic agonists. In this study, we examined the effects of three daily footshock stress sessions on the plasma corticosterone, glucose, glycerol and triacylglycerol levels of fed, conscious male rats, and on the plasma glucose, glycerol and triacylglycerol levels of the same rats following iv infusions of beta-adrenergic agonists (isoproterenol: 0.4 nmol kg-1 min-1, noradrenaline: 5.0 microg kg-1 day-1, and BRL 37344 ([+/-]-[4-(2-[(2-[3-chlorophenyl]-2-hydroxyethyl)amino]propyl)phenoxy]acetic acid), a selective beta3-adrenoceptor agonist: 0.4 nmol kg-1 min-1). Plasma corticosterone levels increased significantly after each stress session, while triacylglycerol levels increased after the first session and glucose increased after the second and third sessions. Glycerol levels were unaltered after stress. These results suggest that repeated footshock stress may induce a metabolic shift from triacylglycerol biosynthesis to glucose release by hepatic tissue, with glycerol serving as one of the substrates in both pathways. Stressed rats were more sensitive to infusion of noradrenaline plus prazosin and to infusion of isoproterenol, with elevated plasma glucose, glycerol and triacylglycerol levels. The higher sensitivity of stressed rats to isoproterenol and noradrenaline was probably related to the permissive effect of plasma corticosterone. Only BRL 37344 increased plasma glycerol levels in stressed rats, probably because beta3-adrenoceptors are not involved in hepatic triacylglycerol synthesis, thus allowing glycerol to accumulate in plasma.

Stress-induced alteration in the lipolytic response to beta-adrenoceptor agonists in rat white adipocytes.

We analysed the sensitivity to beta-adrenoceptor agonists in epididymal adipose cells from rats submitted to a stress protocol previously reported to induce alterations in sensitivity to catecholamines in cardiac tissue from rats. Food intake and body weight were lower, whereas adipocytes basal lipolysis was higher (control: 0.59 +/- 0.04; stress: 1.00 +/- 0.11, micromol glycerol/100 mg total lipids/100 min) in stressed compared to control rats. The responses to isoprenaline (pD(2) control: 7.46 +/- 0.11; stress: 8.11 +/- 0.17), adrenaline (pD(2) control: 5.78 +/- 0. 20; stress: 6.13 +/- 0.18), and salbutamol (pD(2) control: 5.64 +/- 0.28; stress: 5.92 +/- 0.34) were sensitized, and the lipolytic responses to norepinephrine (pD(2) control: 6.98 +/- 0.13; stress: 6. 41 +/- 0.12) and to BRL37344 (pD(2) control: 8.43 +/- 0.19; stress: 7.54 +/- 0.21) were desensitized. Responses to the higher concentration (100 microm) of isoprenaline (control: 1.80 +/- 0.18; stress: 2.24 +/- 0.10 micromol glycerol/100 mg total lipids/100 min), epinephrine (control: 1.64 +/- 0.17; stress: 2.24 +/- 0.14 micromol glycerol/100 mg total lipids/100 min), salbutamol (control: 0.65 +/- 0.11; stress: 1.21 +/- 0.41 micromol glycerol/100 mg total lipids/100 min), and d-butyryl-cAMP (control: 1.59 +/- 0.17; stress: 2.72 +/- 0.25) were significantly enhanced in adipocytes from stressed rats. pD(2) or maximum response to CGP12177 were not altered. Supersensitivity to isoprenaline was abolished by 50 nm ICI118,551 but was not modified by 100 nm metoprolol. However, subsensitivity to norepinephrine and to BRL37344 was abolished by 100 nM metoprolol. Our results suggest that in epididymal adipocytes from stressed rats there is a desensitization of the response to adrenoceptor agonists mediated by beta(1)-adrenoceptors together with a sensitization of the response mediated by beta(2)-adrenoceptors. beta(3)-adrenoceptors seem to be resistant to the stress effect.

Anti-ulcerogenic mechanisms of a lyophilized aqueous extract of Dalbergia monetaria L. in rats, mice and guinea-pigs.

The decoction of Dalbergia monetaria L. is popularly used in Brazil for the treatment of gastric ulcer and the lyophilized aqueous extract (LAE) of D. monetaria has significant anti-ulcerogenic activity and inhibits gastric ulcer lesions induced by pylorus-ligature, ethanol and hypothermic-restraint stress. This work was conducted to identify the antiulcerogenic mechanisms of action of the LAE of D. monetaria. We analysed the effect of the LAE on prostaglandin E2 (PGE2) synthesis and on the characteristics (pH, volume and total acid content) of gastric juice. The antagonism between the LAE and histamine or carbachol was also analysed. The LAE increased gastric mucosal PGE2 synthesis compared with control (89.7+/-21.5 and 52.6+/-11.8 pg mg(-1), respectively) as assayed by enzyme immunoassay in the rat stomach. The LAE reduced the total acid content of gastric juice, but did not modify pH or gastric volume significantly, in Shay rats. Dose-response curves to histamine were shifted to the right in guinea-pig isolated right atria (pD2 values were 5.77+/-0.2 and 5.42+/-0.3, respectively, in the absence and presence of the LAE), with a significant reduction in maximum response (140+/-15.1 and 98+/-13.0, respectively). The same effect was observed when the agonist was isoprenaline. The LAE had no effect on the dose-response curve to carbachol in rat fundus strips. Thus, the protective effect of the LAE on induced gastric lesions might be because of synergistic effects, e.g. increased PGE2 synthesis and antagonism of H2 histamine and beta-adrenergic receptors, reducing gastric acid secretion. Increased PGE2 synthesis results in increased protection, and antagonism of H2 histamine and beta-adrenergic receptors reduces aggressive factors against the gastric mucosa.

Antiulcerogenic mechanisms of dehydrocrotonin, a diterpene lactone obtained from Croton cajucara.

The bark of Croton cajucara Benth, is used in Brazilian folk medicine as an infusion to treat gastrointestinal disorders. The aim of the present study was to assess the mechanisms involved in the antiulcerogenic activity of dehydrocrotonin (DHC), a diterpene isolated from C. cajucara bark. We studied the effects of DHC on pylorus ligature (Shay) in mice treated with the drug (100 mg/kg) by the intraduodenal route. DHC did not induce any alteration in gastric volume in Shay mice but modified the pH and total acid concentration of gastric juice. Incubation of gastric juice with DHC did not reduce gastric acidity compared to control. We also investigated the effects of DHC on the response to histamine of right atria isolated from guinea pigs and on the response to carbachol of stomach fundus strips from rats. The concentration-response curves for the chronotropic effect of histamine in guinea pig right atria were shifted to the right, with a significant decrease in the maximum response, in the presence of DHC. Similar results were obtained with DHC (30 microM) for the concentration-response curves to carbachol in the isolated rat stomach. The ability of DHC to increase PGE2 release from rat stomach mucous cells was also studied. We observed that DHC induced a significant increase in PGE2 production (60% compared to control). In addition, the effects of DHC on the healing of acetic acid-induced gastric ulcer in rats were evaluated 14 days after acid injection. Oral administration of DHC (100 mg/kg per day) for 14 consecutive days had no effect on gastric ulcer healing in rats. Thus, the protective effect of DHC on induced gastric lesions could be due to synergistic effects, e.g., an increase in PGE2 release and non-competitive antagonism of H2-receptors and of muscarinic receptors. Whereas the former result represents an increase in the protective factors, the latter one shows a decrease in the aggressive factors against the gastric mucosa.

Involvement of nitric oxide in the smooth muscle tone of the isolated canine spleen and the responses to acetylcholine and substance P.

1. The canine isolated spleen was perfused at constant flow with warmed (37 degrees C) Krebs solution while the splenic arterial perfusion pressure (SAPP) and spleen weight were recorded continuously. An augmented smooth muscle tone was maintained by a continuous intra-arterial infusion of noradrenaline (0.01-0.1 mumol min-1) throughout the experiment. 2. Intra-arterial infusion of indomethacin (5.6 microM) significantly elevated (P < 0.05) the augmented vascular tone and the subsequent infusion of L-NAME (10 microM) further raised this vascular tone significantly (P < 0.01). 3. The splenic vasoconstrictor response to L-NAME was significantly (P < 0.05) reduced by the subsequent infusion of L-arginine (300 microM) but not of D-arginine (300 microM). 4. Neither L-NAME nor D-NAME had any effect on the basal vascular tone or the spleen weight in conditions of either basal or augmented tone. 5. Bolus injection of acetylcholine, substance P, sodium nitroprusside and isoprenaline caused short-lasting reductions in the SAPP. 6. The splenic vasodilator responses to ACh and SP, but not those to SNP and ISO, were significantly (P < 0.05) reduced by the infusion of L-NAME (10 microM), methylene blue (30 microM) but not of D-NAME (10 microM). 7. The reductions in the vasodilator responses to ACh and SP caused by L-NAME were partially reversed by L-arginine (300 microM), but not by D-arginine (300 microM). 8. The results demonstrate the contribution of nitric oxide (NO) release to the maintenance of the augmented splenic vascular tone and also the contribution of NO to the splenic vasodilator responses to ACh and SP.

Characterisation of functional endothelin receptors in the canine isolated perfused spleen.

The endothelin receptor subtypes involved in the vasoconstriction, capsular smooth muscle contraction, prostaglandin E2 and prostacyclin release induced by endothelin-1 have been investigated in the canine isolated perfused spleen using both the endothelin ETA receptor antagonist FR 139317 and the endothelin ETB receptor agonist IRL 1620. THe isolated canine spleen was perfused with warmed (37 degrees C) and oxygenated (95% O2/5% CO2) Krebs solution at constant flow with continuous recording of splenic arterial perfusion pressure and spleen weight. Samples of splenic venous effluent were collected to determine the amounts of prostaglandin E2 and prostacyclin, measured by radioimmunoassay. Endothelin-1 (4-200 pmol) and IRL 1620 (20-1000 pmol) dose-dependently increased splenic arterial perfusion pressure but the former was more potent on a molar basis (the molar dose ratio IRL/endothelin-1 required to increase splenic arterial vascular resistance by 25% was approximately 33). The infusion of the nitric oxide inhibitor N omega-nitro-L-arginine methyl ester (10 microM), but not of the enantiomer N omega-nitro-D-arginine methyl ester, significantly potentiated the increase in splenic arterial vascular resistance induced by endothelin-1. The infusion of FR 139317 (1 microM) markedly attenuated the increased splenic arterial perfusion pressure induced by endothelin-1 without affecting that evoked by IRL 1620. At the highest dose (200 pmol), endothelin-1 induced a small but significant capsule contraction as reflected by the reduction in the spleen weight. The infusion of FR 139317 (1 microM) abolished this contractile effect. IRL 1620 (in doses up to 1000 pmol) did not significantly affect the capsule tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of endothelin ETA and ETB receptors in the arterial vasculature of the isolated canine liver.

The vascular effects of endothelin-1 (ET-1; ETA/ETB agonist), sarafotoxin 6b (S6b; ETA agonist), and IRL 1620 (ETB agonist) were investigated in the isolated canine liver arterial circuit before and after infusions of indomethacin (cyclo-oxygenase inhibitor) and N omega L-nitro arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor). Norepinephrine (NE) was used as vasconstrictor control agent. The portal vein, hepatic artery, and vena cava were cannulated in vitro and the liver was perfused via the hepatic artery and portal vein with oxygenated (95%) O2/5% CO2) Krebs solution at 37 degrees C. Intra-arterial bolus injections of either ET-1 (0.4-400 pmol) or S6b (0.4-400 pmol) induced dose-dependent and long-lasting vasoconstriction accompanied by significant prostacyclin release. The vasoconstrictor responses to these peptides were slightly increased during infusion of indomethacin. Subsequent infusion of L-NAME potentiated both ET-1- and S6b-induced vasoconstriction (p < 0.05). IRL 1620 (up to 1.2 nmol) had no effect on the hepatic arterial vascular resistance even during indomethacin and L-NAME infusions. Infusion of the ETA receptor antagonist FR-139317 (0.3 microM) markedly reduced both ET-1- and S6b-induced vasoconstriction without affecting that evoked by NE. Our results indicate that pressor responses to ET-1 and S6b in the isolated canine liver are modulated by concomitant release of vasodilator mediators, including prostacyclin and nitric oxide. These effects appear to depend primarily on the activation of ETA receptor subtypes. IRL 1620 (but not ET-1) induced a significant release of hemoglobin into the venous effluent, suggesting that ETB receptors are located in the venous side of the intrahepatic circulation.

The effects and molar potency of iloprost, U46619 and sodium nitroprusside on capsular and vascular smooth muscle of the isolated perfused canine spleen.

The isolated canine spleen was perfused at constant flow with continuous recording of splenic arterial perfusion pressure (SAPP) and spleen weight. Intra-arterial injections of the thromboxane A2 (TXA2) mimetic U46619 caused dose-related increases in splenic arterial perfusion pressure (SAPP) of short duration (ED50 0.31 nmol). There were very small changes in spleen weight accompanying any of the vasoconstrictor responses to U46619. The stable analogue of prostacyclin, iloprost, caused dose-dependent reductions in SAPP (ED50 1.3 nmol) indicating vasodilation. There were no changes in spleen weight to any doses of iloprost indicating a lack of action on capsular smooth muscle. Similarly, the nitric oxide (NO) mimetic sodium nitroprusside caused dose-related reductions in SAPP of short duration (ED50 5.8 nmol). No changes in spleen weight accompanied splenic vasodilator responses to any dose of sodium nitroprusside (SNP). The results indicate the potential actions and intrinsic potency of three endogenous vasoactive substances and provide information about their relative roles in the control of the splenic microcirculation in situations when they are released.

Modulation by endogenous prostanoids of the vasoconstrictor activity of endothelin-1 in the canine isolated, perfused spleen.

1. Endothelin-1 (ET-1, 0.4-200 pmol) was injected into the arterial circuit of the isolated perfused spleen of the dog in which splenic arterial perfusion pressure and spleen weight were recorded continuously. 2. Serial collection was made of splenic venous effluent before and after intra-arterial injection of ET-1 and assayed by direct radioimmunoassay for prostaglandin E2 (PGE2), 6-oxo-PGF1 alpha and thromboxane B2 (TXB2). 3. ET-1 caused graded arterial vasoconstriction of prolonged duration with small reductions in spleen weight at higher doses. 4. ET-1 cause a dose-related release of PGE2, 6-oxo-PGF1 alpha and TXB2 into the splenic venous effluent. The mean peak increase above the basal levels following 200 pmol of ET-1 was 800% for PGE2, 233% for 6-oxo-PGF1 alpha and 205% for TXB2. 5. Intra-arterial infusion of indomethacin significantly reduced the basal release of all three eicosanoids and significantly elevated the basal splenic vascular resistance. The release of all three eicosanoids in response to ET-1 and adrenaline (Ad) was significantly reduced by indomethacin and the accompanying increases in the splenic arterial vascular resistance were significantly potentiated at low doses of ET-1. The splenic arterial vascular responses to Ad were unchanged by indomethacin infusion. 6. These results indicate that the release of eicosanoids may modulate the splenic vascular responses to ET-1.

Canatoxin triggers histamine secretion from rat peritoneal mast cells.

Canatoxin, a toxic protein present in the seeds of Canavalia ensiformis, induces the secretion of serotonin, dopamine and insulin through activation of the lipoxygenase pathway. The purpose of the present study was to verify if canatoxin causes histamine release from rat peritoneal mast cells and to perform a detailed study of this phenomenon. Our results indicate that canatoxin is capable of activating mast cells to release histamine. The process is time- and concentration-dependent, occurs without cell damage and requires metabolic energy as well as the presence of divalent cations (Ca2+ and Mg2+). Optimal release occurs at 37 degrees C and at physiological pH. Extremes of temperature (0 degree C and 45 degrees C) inhibit the process. We conclude that canatoxin induces histamine release from rat peritoneal mast cells by an active secretory process.