Effect of steviol glycosides on cardio-vascular systems
Apart from mild reduction of arterial blood pressure in hypertensive subjects, no effect of Stevioside in cardiovascular systems has been reported.
Boeckh and Humboldt (1981) reported that Stevia extracts reduced heart rate and mean arterial blood pressure in humans. Melis (1995) found that aqueous extracts fed to rats for 40–60 days produced hypotension, the mean arterial pressure falling from 110 mm Hg to 90 mm Hg over the 40- day-treatment period.
Lee et al (2001) showed that intraperitoneal injection of stevioside 25 mg/kg has antihypertensive effect in spontaneously hypertensive rats. In isolated aortic rings from normal rats, stevioside could dose-dependently relax the vasopressin-induced vasoconstriction in both the presence and absence of endothelium. However, stevioside had no effect on phenylephrine- and KCl-induced phasic vasoconstriction. In addition, stevioside lost its influence on vasopressin-induced vasoconstriction in Ca(2+)-free medium. The results indicate that stevioside caused vasorelaxation via an inhibition of Ca(2+) influx into the blood vessel.
Liu et al (2003) reported that after nasogastric administration of stevioside powder (200 mg/kg), the blood pressure of healthy mongrel dogs began to significantly decrease at 60 min and returned to baseline level at 180 min. The reduction of blood pressure was more rapid (at 5-10 min) and effective after intravenous injection. However, no significant change of blood pressure was noted after injection through left vertebral artery, implicating that the hypotensive effect is not related to the central nervous system. Stevioside also showed significant hypotensive effects in renal hypertensive dogs, in a dose-dependent manner. In cultured rat aortic smooth muscle cells (A7r5 cell line), stevioside can dose-dependently inhibit the stimulatory effects of vasopressin and phenylephrine on intracellular Ca(2+) in a calcium-containing medium. However, no intracellular Ca(2+) inhibitory effect was observed in calcium-free medium, implicating that stevioside may inhibit the Ca(2+) influx from extracellular fluid.
The interaction of aqueous solutions of stevioside and bile acids with cardioactive drugs was studied by Vasovic et al (2006) in rats by registering changes in their electrocardiograms (ECG). In their study, Wistar rats of both sexes received daily doses of 20 mg/kg (i.p.) of an aqueous solution of stevioside or physiological solution (controls), then were narcotized with urethane and connected to the ECG apparatus for the first recording. The jugular vein was prepared and connected to an infusion pump to administer one of the drugs: adrenaline (0.1 mg/ml), verapamil (2.5 mg/ml) or metoprolol (1 mg/ml) to rats in both groups, while recording their ECGs. In the second part of the study, the animals were treated in the same way but instead of the stevioside solution received a single dose of 4 mg/kg of monoketocholic acid methyl ester (ME) or sodium salt of the same bile acid (MKHNa), 30 minutes before cardioactive drug infusion. The infusion rate of cardioactive drugs was 0.2 ml/min, except for verapamil (0.1 ml/min). The events observed on ECG recordings were the first myocardial reaction to drug infusion, the second longer-lasting reaction (observed as more extended extrasystoles, decrease in intensity of the QRS complex, or changes in heart rate frequency), and toxicity effect. In the control animals, adrenaline induced a decrease in heart rate frequency at a dose of 0.094 mg/kg, while with stevioside-pretreated rats this effect appeared significantly earlier (at a dose of 0.018 mg/kg). No toxic effect of adrenaline was observed, either in control or stevioside-pretreated group. Bile acids caused no changes in myocardial reaction to adrenaline. Only in the group of animals that received MKHNa, a significant decrease in the QRS complex was observed. Finally, the infusion of st