Vrolijk Misha F, van Essen Helma, Opperhuizen Antoon, Bast Aalt, Janssen Ben J
Department of Pharmacology & Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Faculty of Science and Engineering, Maastricht University Campus Venlo, Venlo, The Netherlands.
Br J Pharmacol. 2020 Apr;177(8):1841-1852. doi: 10.1111/bph.14955. Epub 2020 Feb 3.
The flavonoid quercetin increased the in vitro potency of the α -antagonist tamsulosin to reduce phenylephrine-dependent arterial contractions by 10-fold. To examine if this supplement-drug interaction luxates hypotensive and orthostatic events in vivo, several set of studies were conducted in spontaneously hypertensive (SHR) and normotensive (Wistar Kyoto [WKY]) rats.
First, in rats pretreated with quercetin or its vehicle, responses to phenylephrine and tamsulosin were examined. Second, tamsulosin-induced changes in renal, mesenteric, hindquarter and carotid conductance were compared in quercetin- and vehicle-treated rats instrumented with Doppler flow probes. Animals were also placed on a tilt table to record regional haemodynamic changes to orthostatic challenges. Third, adult SHR were instrumented with telemeters to measure 24-hr patterns of BP. Recordings were made before and during a 5-week oral treatment of quercetin. Finally, pre-hypertensive SHR were treated with quercetin from 4 to 8 weeks of age and arterial pressure was measured at 8 and 12 weeks.
Pretreatment with quercetin did not influence the responses to phenylephrine and tamsulosin, in neither WKY nor SHR. While tamsulosin treatment and tilting lowered BP and increased conductance in all vascular beds, effect size was not influenced by pretreatment with quercetin. Prolonged treatment with quercetin, in either prehypertensive SHR or adult SHR with established hypertension did not lower BP.
Cumulatively, these data demonstrate that quercetin does not amplify haemodynamic effects of tamsulosin or tilting in vivo in rats and has no effect on BP development in SHR.
类黄酮槲皮素可使α受体拮抗剂坦索罗辛在体外降低去氧肾上腺素引起的动脉收缩的效力提高10倍。为了研究这种补充剂与药物的相互作用在体内是否会引发低血压和体位性事件，我们在自发性高血压（SHR）大鼠和正常血压（Wistar Kyoto [WKY]）大鼠中进行了几组研究。
首先，在预先用槲皮素或其赋形剂处理的大鼠中，检测对去氧肾上腺素和坦索罗辛的反应。其次，在植入多普勒血流探头的经槲皮素和赋形剂处理的大鼠中，比较坦索罗辛引起的肾、肠系膜、后肢和颈动脉传导变化。还将动物置于倾斜台上，记录体位性刺激引起的局部血流动力学变化。第三，给成年SHR植入遥测仪以测量24小时血压模式。在槲皮素口服治疗5周之前和期间进行记录。最后，对高血压前期SHR在4至8周龄时用槲皮素治疗，并在8周和12周时测量动脉血压。
在WKY大鼠和SHR大鼠中，槲皮素预处理均不影响对去氧肾上腺素和坦索罗辛的反应。虽然坦索罗辛治疗和倾斜可降低血压并增加所有血管床的传导，但效应大小不受槲皮素预处理的影响。在高血压前期SHR或已患高血压的成年SHR中，长期用槲皮素治疗均未降低血压。
总体而言，这些数据表明槲皮素在大鼠体内不会增强坦索罗辛或倾斜引起的血流动力学效应，对SHR的血压发展也无影响。
