Abstract
Boldine, 2,9-dihydroxy-1,10-dimethoxyaporphine, is the main alkaloid found in the leaves and bark of Peumus boldus Molina. In recent years, boldine has demonstrated several pharmacological properties that benefit endothelial function, blood pressure control, and reduce damage in kidney diseases. However, the renal vasodilator effects and mechanisms remain unknown. Herein, perfused rat kidneys were used to study the ability of boldine to induce vasodilation of renal arteries. For that, left kidney preparations with and without functional endothelium were contracted with phenylephrine and received 10–300 nmol boldine injections. The preparations were then perfused for 15 min with phenylephrine plus L-NAME, indomethacin, KCl, tetraethylammonium, glibenclamide, apamin, charybdotoxin, or iberiotoxin. In 30, 100, and 300 nmol doses, boldine induced a dose-and endothelium-dependent relaxing effect on the renal vascular bed. No vasodilator effects were observed in preparations lacking functional endothelium. While the inhibition of the cyclooxygenase enzyme through the addition of indomethacin did not cause any change in the vasodilating action of boldine, the nonselective nitric oxide synthase inhibitor L-NAME fully precluded the vasodilatory action of boldine at all doses tested. The perfusion with KCl or tetraethylammonium (nonselective K+ channels blocker) also abolished the vasodilatory effect of boldine, indicating the participation of K+ channels in the renal action of boldine. The perfusion with glibenclamide (selective ATP-sensitive K+ channels blocker), iberiotoxin (selective high-conductance Ca2+-activated K+ channel blocker), and charybdotoxin (selective high- and intermediate-conductance Ca2+-activated K+ channel blocker) did not modify the vasodilatory action of boldine. On the other hand, the perfusion with apamin (selective small-conductance Ca2+-activated K+ channel blocker) completely prevented the vasodilatory action of boldine at all doses tested. Together, the present study showed the renal vasodilatory properties of boldine, an effect dependent on the generation of nitric oxide and the opening of a small-conductance Ca2+-activated K+ channel.
Highlights
Peumus boldus Molina, popularly known as “boldo” or “boldu”, is a tree species belonging to the Monimiaceae family and native to central and southern Chile, where it occurs abundantly
Most of the pharmacological studies of boldo describe the activities observed for the alkaloid boldine, defined as the main component of boldo tea [4]. e concentration of alkaloids in boldo leaves is estimated at 0.4%, and the concentration of boldine can reach more than 12% [5]
Considering the need for new approaches to the treatment of hypertension or contributing to the renoprotective actions against hypertension, this study aimed to investigate boldine’s vasodilatory action by using an isolated and perfused rat kidney model to verify the hypothesis that boldine causes the direct relaxation of renal arteries. e mechanisms responsible for renal vasodilator actions were explored
Summary
Peumus boldus Molina, popularly known as “boldo” or “boldu”, is a tree species belonging to the Monimiaceae family and native to central and southern Chile, where it occurs abundantly. Boldine has been shown to possess antioxidant activity and anti-inflammatory effects, which is why it is often studied for oxidative stress-associated diseases. The protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats has been described [6], and the reduction on oxidative stress to induce its gastroprotective properties [7]. As for the pharmacological action on the cardiovascular and renal systems to control hypertension and pathologies such as diabetes, studies have shown the action of boldine in improving the endothelial function in diabetic mice through the inhibition of vascular oxidative stress and endothelial dysfunction [8]. Studies have demonstrated that boldine treatment exerts endothelial protective effects in spontaneously hypertensive rats through the inhibition of NADPH-mediated superoxide production [9]. Boldine improved kidney damage in renovascular hypertension induced by the Goldblatt two-kidney one-clip model [10] and showed a renoprotective action in streptozotocin-induced diabetes in rats [11]
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