Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats.

Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h), according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin) and p-aminohipuric acid clearance (C PAH) were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+), fractional potassium excretion (FeK+), urinary flow as percent of glomerular filtration rate (V/GFR) and glucose clearance (C G) when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S) was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose.

Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats / O efeito do esteviol, um glicosídeo da Stevia rebaudiana, no clearance da glicose em ratos

Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h), according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin) and p-aminohipuric acid clearance (C PAH) were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+), fractional potassium excretion (FeK+), urinary flow as percent of glomerular filtration rate (V/GFR) and glucose clearance (C G) when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S) was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose.

Stevia rebaudiana, uma planta da América do Sul usada como adoçante natural, parece exercer efeitos benéficos para a saúde humana, incluindo ação anti-hipertensiva e anti-hiperglicêmica. No presente trabalho objetivamos avaliar a excreção renal do esteviol, uma aglicona extraída das folhas de S. rebaudiana, e elucidar a participação deste composto na excreção renal de glicose em ratos, o qual foi sugerido agir no sistema de transporte tubular renal Na+-glicose. O esteviol foi obtido por hidrólise enzimática com pectinase. Foram usados 30 ratos Wistar machos e pesando 345 g. Após um período controle, o esteviol foi infundido iv em três doses (0,5, 1,0 e 3,0 mg.kg-1/h) de acordo com técnicas clássicas de clearance. Durante os experimentos não houve alterações significantes no clearance da inulina (Cin) e do ácido-aminohipúrico (C PAH). A administração de esteviol resultou em um aumento estatisticamente significante na excreção fracional de sódio (FeNa+) e potássio (FeK+ ), no fluxo urinário como porcentagem da taxa de filtração glomerular (V/GFR) e do clearance de glicose (C G) quando comparados aos animais controles, embora estes efeitos estivessem ausentes na dose de 0,5 mg.kg-1/h. O clearance de esteviol (C S) foi maior que o Cin e menor que o C PAH em todas as doses usadas nos experimentos. Os dados sugerem a secreção de esteviol pelo epitélio tubular renal, causando diurese, natriurese, caliurese e uma redução na reabsorção tubular renal de excreção de glicose.

Effect of strenuous maternal exercise before and during pregnancy on rat progeny renal function.

The effects of strenuous exercise before and during pregnancy on the renal function and morphological alterations of the progeny were determined in a study on female Wistar rats. This research was done based on a previous study carried out in our laboratory, which showed morphological alterations in rats submitted to this kind of exercise. As the form is related to the function, the physiological relevance of submitting a pregnant female to a high-intensity exercise training regimen could be explained by the fact that morphological alterations can influence kidney function. The animals were assigned to one of two groups: control animals that did not exercise during pregnancy and trained animals that swam for 120 min 5 days a week for 8 weeks before pregnancy and daily for 60 min over a period of 8 weeks starting on the second day of pregnancy. Seven rats of each group were analyzed for morphological alterations and for renal function. The progeny of the rats used for morphological evaluation were born by cesarean section and the progeny of the animals used to evaluate renal function were born normally. The progeny were two months old when renal function was evaluated. Fertility and morbidity were the same for both groups. Strenuous maternal exercise had no significant influence on glomerular filtration rate (GFR) but renal plasma flow was lower in the progeny of the trained group (mean +/- SD, 16.65 +/- 3.77 ml min(-1) kg(-1)) compared to the progeny of the control group (33.42 +/- 2.56 ml min(-1) kg(-1)). Antidiuretic and antinatriuretic effects on the progeny of the trained group were observed, since urine flow as percentage of GFR and the fraction of urinary sodium excretion were lower in this group (1.38 +/- 0.10 and 0.60 +/- 0.04%, respectively) compared to the progeny of the control group (2.36 +/- 0.11 and 1.55 +/- 0.20%, respectively). Moreover, in this exercise program, fetuses from trained animals were small-sized (2.45 +/- 0.19 vs 4.66 +/- 2.45 g for control animals) and showed lower differentiation compared to fetuses from the control group. These effects were probably caused by caloric restriction, hypoxia and reduction of umbilical cord length.

Effect of strenuous maternal exercise before and during pregnancy on rat progeny renal function

The effects of strenuous exercise before and during pregnancy on the renal function and morphological alterations of the progeny were determined in a study on female Wistar rats. This research was done based on a previous study carried out in our laboratory, which showed morphological alterations in rats submitted to this kind of exercise. As the form is related to the function, the physiological relevance of submitting a pregnant female to a high-intensity exercise training regimen could be explained by the fact that morphological alterations can influence kidney function. The animals were assigned to one of two groups: control animals that did not exercise during pregnancy and trained animals that swam for 120 min 5 days a week for 8 weeks before pregnancy and daily for 60 min over a period of 8 weeks starting on the second day of pregnancy. Seven rats of each group were analyzed for morphological alterations and for renal function. The progeny of the rats used for morphological evaluation were born by cesarean section and the progeny of the animals used to evaluate renal function were born normally. The progeny were two months old when renal function was evaluated. Fertility and morbidity were the same for both groups. Strenuous maternal exercise had no significant influence on glomerular filtration rate (GFR) but renal plasma flow was lower in the progeny of the trained group (mean ñ SD, 16.65 ñ 3.77 ml min-1 kg-1) compared to the progeny of the control group (33.42 ñ 2.56 ml min-1 kg-1). Antidiuretic and antinatriuretic effects on the progeny of the trained group were observed, since urine flow as percentage of GFR and the fraction of urinary sodium excretion were lower in this group (1.38 ñ 0.10 and 0.60 ñ 0.04 percent, respectively) compared to the progeny of the control group (2.36 ñ 0.11 and 1.55 ñ 0.20 percent, respectively). Moreover, in this exercise program, fetuses from trained animals were small-sized (2.45 ñ 0.19 vs 4.66 ñ 2.45 g for control animals) and showed lower differentiation compared to fetuses from the control group. These effects were probably caused by caloric restriction, hypoxia and reduction of umbilical cord length.

Effect of crude extract of Stevia rebaudiana on renal water and electrolytes excretion.

To evaluate the effect of crude extract of Stevia rebaudiana on renal water, Na+ and K+ excretion, male Wistar rats (250-350 g each) under antidiuresis or water diuresis conditions, were evaluated. During intravenous infusion of the extract (0.05 mg/min/100 g) no significant differences were detected in mean arterial pressure or renal hemodynamics parameters. In contrast, fractional water and sodium excretion and solute clearance increased significantly, in both groups of animals. In antidiuresis rats the extract significantly increased reabsorption of water by the collecting duct and in water diuresis animals the extract significantly increased free water clearance. The data suggest preferential action of the extract in the proximal tubular cells involved with salt transport mechanism.

Effects of chronic administration of Stevia rebaudiana on fertility in rats.

A study conducted on prepubertal male rats showed that chronic administration (60 days) of a Stevia rebaudiana aqueous extract produced a decrease in final weight of testis, seminal vesicle and cauda epididymidis. In addition, the fructose content of the accessory sex glands and the epididymal sperm concentration are decreased. Stevia treatment tended to decrease the plasma testosterone level, probably by a putative affinity of glycosides of extract for a certain androgen receptor, and no alteration occurred in luteinizing hormone level. These data are consistent with the possibility that Stevia extracts may decrease the fertility of male rats.

Effects of Steviol on renal function and mean arterial pressure in rats.

The effects of steviol, obtained from Stevia rebaudiana, on renal function were investigated using clearance techniques in Wistar rats. Steviol (0.5, 1.0 and 3.0 mg/kg(-1)/h(-1)iv) elicited no significant changes in mean arterial pressure (MAP), glomerular filtration rate (GFR) and renal effective plasma flow (ERPF). The steviol infusion (1.0 and 3.0 mg/kg(-1)/h(-1)), however, induced a significant increase in the fractional sodium excretion (FeNa(+)), fractional potassium excretion (FeK(+)), and urinary flow as percent of glomerular filtration rate (V/GFR) when compared to controls. The data suggest that the steviol may affect salt and water transport in renal tubules.

A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats.

The effect of S. rebaudiana extract on renal function was evaluated in normotensive and in experimental renal hypertensive rats (GII) using clearance techniques. Experiments were performed on male Wistar rats weighing 300-330 g (10 animals per group). Goldblatt GII experimental hypertension was induced by placing a silver clip with an internal gap of 0.25 mm around the left renal artery under ether anesthesia. The contralateral kidney was left untouched. Stevia was administered 10-12 weeks after clipping. Oral-administration of Stevia extract, corresponding to 2.67 g dry leaves/day for 30 days, resulted in a significant decrease in mean arterial pressure in both the normo-(N) and hypertensive rats (H) (N rats: 113 +/- 3.0 mmHg in the control (C) group vs 69.5 +/- 4.0 mmHg in the Stevia (S) group; H rats: 155 +/- 3.0 mmHg in C vs 108 +/- 4.0 mmHg in S; P < 0.05). Glomerular filtration rate was constant in the N rats and increased significantly in the H rats after Stevia treatment 16.47 +/- 1.29 vs 14.2 +/- 1.33 ml min-1 kg-1 in the C and S groups, respectively, P < 0.05). Normo- and hypertensive rats presented an increase in renal plasma flow following oral Stevia administration (N rats: 16.4 +/- 3.10 ml min-1 kg-1 in the C group vs 33.3 +/- 3.20 ml min-1 kg-1 in the S group. P < 0.05; H rats: 19.30 +/- 2.45 ml min-1 kg-1 in the C group vs 37.0 +/- 3.93 ml min-1 kg-1 in the S group, P < 0.05). Stevia administration provoked an increase in urinary flow in both N and H animals (1.37 +/- 0.08% vs 2.32 +/- 0.11%, P < 0.05 and 1.47 +/- 0.07% vs 2.96 +/- 0.13%, P < 0.05 in N and H rats, respectively). Sodium excretion increased in N and H animals after Stevia treatment (N rats: 0.61 +/- 0.07% in the C group vs 1.55 +/- 0.20% in the S group, P < 0.05; H rats: 0.70 +/- 0.10% in the C group vs 2.22 +/- 0.45% in the S group, P < 0.05). These results are consistent with impairment of a renal autoregulation mechanism in this hypertensive model after Stevia administration. In conclusion, it was shown that Stevia extract, at doses higher than used for sweetening purposes, is a vasodilator agent in normo- and hypertensive animals.

A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats

The effect of S. rebaudiana extract on renal function was evaluated in normotensive and in experimental renal hypertensive rats (GII) using clearance techniques. Experiments were performed on male Wistar rats weighing 300-330 g (10 animals per group). Goldblatt GH experimental hypertension was induced by placing a silver clip with an internal gap of 0.25 mm around the left renal artery under ether anesthesia. The contralateral kidney was left untouched. Stevia was administered 1012 weeks after clipping. Oral administration of Stevia extract, corresponding to 2.67 g dry leaves/day for 30 days, resulted in a significant decrease in mean arterial pressure in both the normo- (N) and hypertensive rats (H) (N rats: 113 ñ 3.0 mmHg in the control (C) group vs 69.5 ñ 4.0 mmHg in the Stevia (S) group; H rats: 155 ñ 3.0 mmHg in C vs 108 ñ 4.0 mmHg in S; P<0.05). Glomerular flltration rate was constant in the N rats and increased significantly in the H rats afterStevia treatment (6.47 ñ 1.29 vs 14.2 ñ 1.33 ml min-1 kg-1 in the C and S groups, respectively, P<0.05). Normo- and hypertensive rats presented an increase in renal plasma flow following oral Stevia administration (N rats: 16.4 ñ 3.10 ml min-1 kg-1 in the C group vs 33.3 ñ 3.20 ml min-1 kg-1 in the S group,P<0.05; H rats: 19.30ñ2.45 ml min-lkg-1 in the C group vs 37.0 ñ 3.93 ml min-1 kg-1 in the S group, P<0.05). Stevia administration provoked an increase in urinary flow in both N and H animais (1.37 ñ O.08 per cent vs 2.32 ñ 0.11 per cent P<0.05 and 1.47 ñ 0.07 per cent vs 2.96 ñ O.13 per cent, P<0.05 in N and H rats, respectively). Sodium excretion increased in N and H animals after Stevia treatment (N rats: O.61 ñ O.07 per cent in the C group vs 1.55 ñ 0.20 per cent in the S group, P<0.05; H rats: 0.70 ñ 0.1O per cent in the C group vs 2.22 ñ O.45 per cent in the S group, P<0.05). These results are consistent with impairtnent of a renal autoregulation mechanism in this hypertensive model after Stevia administration. In conclusion, it was shown that Stevia extract, at doses higher than used for sweetening purposes, is a vasodilator agent in - and hypertensive animals.

Chronic administration of aqueous extract of Stevia rebaudiana in rats: renal effects.

The effects of administration of Stevia rebaudiana extracts for 20, 40 and 60 days on renal function and mean arterial pressure in normal Wistar rats were evaluated. Results showed that the Stevia rebaudiana treated rats group for 20 days did not significantly differ from the control group. Chronic administration of a crude extract for 40 and 60 days induced hypotension, diuresis and natriuresis with glomerular filtration rate (GFR) constant. An increase of the renal plasma flow (RPF) was exclusively observed for the group treated for 60 days. The results suggests that oral administration to rats of an aqueous extract of Stevia dried leaves induce systemic and renal vasodilation, causing hypotension, diuresis and natriuresis.

Effect of medium tonicity on transepithelial H(+)-HCO3-fluxes in rat proximal tubule.

1. The effect of luminal and capillary perfusion with hypotonic or hypertonic solutions containing 25 mM NaHCO3 or NaH2PO4 plus NaCl, K+, Ca2+, Mg2+ and acetate at an osmolality of 100 or 500 mosmol kg-1 on rat proximal H+ secretion was estimated by monitoring luminal pH with Sb microelectrodes. The results were compared to perfusions with the same ionic concentration in which tonicity was adjusted to 300 mosmol kg-1 with raffinose. 2. The kinetics of acidification of luminally injected bicarbonate buffer permits evaluations of H(+)-HCO3-fluxes as well as stationary pH gradients; the kinetics of alkalinization of luminally injected acid phosphate buffer indicates H(+)-HCO3-backfluxes from blood to lumen. 3. In alkalinization experiments, luminal perfusion with hypotonic solution during presence of blood in capillaries or hypotonic capillary perfusion leads to a decrease of stationary pH, an increase of alkalinization half-time and consequently a decrease of passive H(+)-HCO3-backflux. 4. In alkalinization experiments, during luminal and/or capillary perfusions with hypertonic solutions, no significant differences in the stationary pH, alkalinization half-time and H(+)-HCO3-backflux were found. 5. During acidification experiments, with both hypo- and hypertonic perfusions, no significant differences in stationary pH, acidification half-time and H(+)-HCO3-flux were observed. 6. Luminal perfusion with hypotonic solution increases specific epithelial resistance in the presence of blood in capillaries. Luminal perfusion with hypertonic solution does not change this parameter. 7. Volume changes, measured by the split-drop method, are slow during the first 30 s and do not explain the increased alkalinization half-time during luminal perfusion with hypotonic solution, since this is the period of fastest pH change. 8. Luminal perfusion with hypotonic solution decreases apparent H+ permeability in the presence of blood or hypotonic solution in capillaries. Hypertonic solutions in all experimental conditions had no significant effect on this parameter. 9. The data indicate that decrease of tonicity of fluids in contact with proximal tubule epithelium affects passive H(+)-HCO3-backflux, which proceeds in part through the shunt path, while acidification (H+ secretion), which is transcellular, is not affected by extracellular tonicity.

Stevioside effect on renal function of normal and hypertensive rats.

Physiological and pharmacological experiments have suggested that stevioside from the leaves of Stevia rebaudiana acts as a typical systemic vasodilator. The effect of stevioside on renal function in both normal and with experimental renal hypertension rats (GII) was evaluated using clearance techniques. Stevioside provoked hypotension, diuresis and natriuresis in both the normal and hypertensive rats. Normal rats presented an increase in renal plasma flow (RPF) and glomerular filtration rate (GFR) constant following stevioside administration. The last effect is in part due to vasodilation of both the afferent and efferent arterioles. Moreover, stevioside infusion in hypertensive rats caused an increase in RPF and GFR. These data are consistent with impairment of a renal autoregulation mechanism in this experimental hypertensive model.

Renal excretion of stevioside in rats.

The renal excretion of stevioside, a glycoside extracted from the leaves of Stevia rebaudiana, and its effect on renal excretion of several substances, was studied through clearance techniques in Wistar rats. After a control period, stevioside was infused iv at four concentrations (4, 8, 12, and 16 mg/kg). During all the experiments no significant changes in inulin clearance (CIn) were observed. The stevioside infusion induced a significant increase in the p-aminohippuric acid clearance (CPAH), fractional sodium excretion (FeNa+), urinary flow as percent of glomerular filtration rate (V/GFR), and glucose clearance (CG) when compared to controls, but these effects were absent with the dose of 4 mg/kg. The stevioside clearance (CS) was higher than the CIn and lower than the CPAH at all the doses employed in this study. These results indicate that the stevioside is secreted by renal tubular epithelium and induces diuresis and natriuresis and a fall in renal tubular reabsorption of glucose.

Influence of calcium on the blood pressure and renal effects of stevioside.

1. The effects of verapamil (V, 0.015 mg/min, i.v.) or CaCl2 (800 mEq/l, 0.025 ml kg-1 min-1, i.v.) on renal function and mean arterial pressure (MAP) were evaluated in male Wistar rats weighing 280-320 g during treatment with stevioside (S, 16 mg kg-1 h-1, i.v.). 2. Verapamil administered to 10 rats significantly increased the hypotensive effect of stevioside on MAP (control, 124 +/- 0.77; S, 96 +/- 1.50; S+V, 67 +/- 0.70 mmHg) and on fractional sodium excretion (control, 0.76 +/- 0.05; S, 1.56 +/- 0.10; S+V, 2.72 +/- 0.25%). Urinary flow, reported as percent glomerular filtration rate (V/GFR), and renal plasma flow (RPF) increased slightly but not significantly during stevioside plus verapamil administration. 3. In contrast, infusion of CaCl2 in 10 rats pretreated with stevioside induced a marked attenuation of MAP (control, 119 +/- 1.83; S, 70 +/- 1.12; S+CaCl2, 109 +/- 1.60 mmHg) and RPF (control, 16.73 +/- 3.76; S, 34.33 +/- 2.55; S+CaCl2, 17.20 +/- 2.87 ml min-1 kg-1). The diuresis and natriuresis induced by stevioside were also inhibited by simultaneous administration of CaCl2. 4. These data are consistent with the view that stevioside acts on arterial pressure and renal function as a calcium antagonist, as is the case for verapamil.

Influence of calcium on the blood pressure and renal effects of stevioside

The effect of verapamil (V, 0.015 mg/min, iv) or Ca Cl2 (800 mEq/l, 0.025 ml kg-1 min-1,iv) on renal function and mean arterial pressure (MAP) were evaluated in male Wistar rats weighing 280-320 g during treatment with stevioside (S, 16 mg kg-1 h-1, iv). Verapamil administered to 10 rats significantly increased the hypotensive effect of stevioside on MAP (control 124 ñ 0.77; S, 96 ñ 1.50; S+V, 67 ñ 0.70 mm Hg) and fractional sodium excretion (control 0.76 ñ 0.05; S, 1.56 ñ 0.10; S+V, 2.72 ñ 0.25%). Urinary flow, reported as percent glomerular filtration rate (V/GRF), and renal plasma flow (RPF) increased slightly but not significantly during stevioside plus verapamil administration. In contrast, infusion of CaCl2 in 10 rats pretreated with stevioside induced a marked attenuation of MAP (control 119 ñ 1.83; S, 70 ñ 1.12; S ñ CaCl2, 109 ñ 1.60 mmHg) and RPF (control, 16.73 ñ 3.76; S, 34.33 ñ 2.55; S+CaCl2, 17.20 ñ 2.87 ml min-1 Kg-1). The diuresis and natriuresis induced by stevioside were also inhibited by simultaneous administration of CaCl2. These data are consistent with the view that stevioside acts on arterial pressure and renal function as a calcium antagonist, as is the case for verapamil

Effect of calcium and verapamil on renal function of rats during treatment with stevioside.

A study conducted on rats using classical clearance techniques and arterial pressure measurements showed that stevioside from Stevia rebaudiana leaves produced a fall in systemic blood pressure, as well as diuresis and natriuresis per milliliter of glomerular filtration rate. Verapamil tended to increase the renal and systemic effects of stevioside. In contrast, an infusion of CaCl2 in rats prepared with stevioside induced a marked attenuation of the vasodilating responses of stevioside. These data are consistent with the possibility that stevioside may act as a calcium antagonist, as is the case for verapamil.

Participation of prostaglandins in the effect of stevioside on rat renal function and arterial pressure.

1. The effect of stevioside on renal function was evaluated by clearance techniques in Wistar rats simultaneously with the effect of indomethacin on the renal action of stevioside. The indomethacin experiments consisted of four consecutive periods: (C) control; (S), in which stevioside (16 mg/kg) was continuously infused; (S+I1) and (S+I2) in which indomethacin was infused systemically without interrupting stevioside infusion. Mean arterial pressure (MAP) and renal function parameters were measured. 2. Administration of stevioside resulted in a statistically significant dose-related decrease in MAP (121 +/- 2.30, N = 7 for 4 mg/kg stevioside to 72 +/- 4.79 mmHg, N = 7 for 16 mg/kg stevioside) and an increase in renal plasma flow (RPF) (10.27 +/- 1.21, N = 7 for 4 mg/kg stevioside to 26.28 +/- 2.87 ml min-1 kg-1, N = 7 for 16 mg/kg stevioside), with no change in glomerular filtration rate (GFR). Stevioside also increased fractional sodium (FeNa+) and potassium (FeK+) excretion as well as urine flow (V/GFR). 3. The decrease in MAP (control, 121 +/- 0.93, N = 7; stevioside, 91 +/- 2.48 mmHg) and increase in RPF (control, 14.21 +/- 1.41, N = 7; stevioside, 32.53 +/- 2.84 mmHg) induced by stevioside (16 mg/kg) were inhibited by simultaneous administration of indomethacin (2 mg/kg), but GFR was not affected. The diuretic, natriuretic and kaliuretic effects of stevioside were also abolished by indomethacin. 4. We conclude that stevioside behaves like a typical vasodilator substance, causing changes in MAP, diuresis, natriuresis and kaliuresis per ml of GFR, and these effects probably depend on prostaglandins.

Participation of prostaglandins in the effect of stevioside on rat renal function and arterial pressure

1. The effect if stevuisude ib renal function was evaluated by clearance tecniques in Wistar rats simultaneously with the effect of indomethacin on the renal action of stevioside. The indomethacin experiments consisted of four consectuve periods: (C) control; (S), in which stevioside (16 mg/Kg) was continously infused; (S+I1) and (S+I2) in which indomethacin was infused systemically without interrupting stevioside infusion. Mean arterial pressure (MAP) and renal function perameters were measured. 2. Administration of stevioside resulted in a statistically significant dose-related decrease in MAP (121 ñ 2.30, N = 7 for 4mg/Kg stevioside to 72 ñ 4.79 mmHg, N = 7 for 16 mg/Kg stevioside) and an increase in renal plasma flow (RPF) (10.27 ñ 1.21, N = 7 for 4 mg/Kg stevioside to 26.28 ñ 2.87 ml min-1 Kg-1, N = 7 for 16 mg/Kg stevioside), with no change in glomerular filtration rate (GFR). Stevioside also increased fractional sodium (FeNa+) and potassium (FeK+) excretion as well as urine flow (V/GFR). 3. The decrease in MAP (control, 121 ñ 0.93, N = 7; stevioside, 91 ñ 2.48 mmHg) and increase in RPF (control, 14.21 ñ 1.41, N = 7; stevioside, 32.53 ñ 2.84 mmHg) induced by stevioside (16 mg/Kg) were inhibited by simultaneous administration of indomethacin (2 mg/Kg) but GFR was not affected. The diuretic, natriuretic and kaliuretic effects of stevioside were also abolished by indomethacin. 4. We conclud that stevioside behaves like a typical vasodilator substance, causing changes in MAP, diuresis, natriuresis and kaliuresis per ml of GFR, and these effects probably depend on prostaglandins