Haemodynamic effects of the flavonoid quercetin in rats revisited.

Misha F Vrolijk,Aalt Bast,Helma Van Essen,Antoon Opperhuizen,Ben J Janssen

doi:10.1111/bph.14955

Abstract

Background and PurposeThe flavonoid quercetin increased the in vitro potency of the α1‐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.Experimental ApproachFirst, 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.Key ResultsPretreatment 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.Conclusions and ImplicationsCumulatively, 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.

Highlights

Epidemiological studies have revealed inverse associations between the intake of dietary flavonoids and mortality from cardiovascular diseases (Geleijnse, Launer, Van der Kuip, Hofman, & Witteman, 2002; Hertog, Feskens, Hollman, Katan, & Kromhout, 1993; Knekt, Jarvinen, Reunanen, & Maatela, 1996; McCullough et al, 2012; Mink et al, 2007; Yochum, Kushi, Meyer, & Folsom, 1999)
We discovered that in isolated mesenteric arteries, quercetin increased the potency of tamsulosin to inhibit phenylephrine-induced contractions by a factor >10 (Vrolijk et al, 2015)
The present study revisited the in vivo haemodynamic effects of quercetin in rats

Summary

| INTRODUCTION

Epidemiological studies have revealed inverse associations between the intake of dietary flavonoids and mortality from cardiovascular diseases (Geleijnse, Launer, Van der Kuip, Hofman, & Witteman, 2002; Hertog, Feskens, Hollman, Katan, & Kromhout, 1993; Knekt, Jarvinen, Reunanen, & Maatela, 1996; McCullough et al, 2012; Mink et al, 2007; Yochum, Kushi, Meyer, & Folsom, 1999). While other studies have explored the antihypertensive effects of quercetin further, controversy exists about the potential mechanisms involved, as well the magnitude of the effect and the potential clinical relevance (Carlstrom et al, 2007; Larson, Symons, & Jalili, 2012; Monteiro, Franca-Silva, Alves, Porpino, & Braga, 2012; Sanchez et al, 2006). This is possibly due to publication bias (Serban et al, 2016), since negative studies on quercetin have been rarely published. To investigate the possible haemodynamic mechanisms involved, four series of experiments were performed assessing acute as well as chronic effects of oral and intravenously administered quercetin in both SHR and Wistar Kyoto (WKY) rats

| METHODS

| Experimental procedures and surgery

| RESULTS

Findings

| DISCUSSION