Diuretic and natriuretic effect of luteolin in normotensive and hypertensive rats: Role of muscarinic acetylcholine receptors

Abstract

Background: Luteolin is a very common phenolic compound found in a wide variety of natural products. Although several biological properties have already been described regarding the beneficial effect of luteolin in the cardiovascular and renal system, no scientific research explored its potential effect as a diuretic agent in experimental trials.

Methods: Groups of male normotensive (NTR) and spontaneously hypertensive rats (SHR) were orally treated with vehicle, hydrochlorothiazide or luteolin. In another experimental set, in order to verify the possible mechanisms of luteolin-induced diuresis, NTR were treated with vehicle, hydrochlorothiazide, amiloride, L-NAME, indomethacin or atropine, 1h before receiving luteolin. The cumulative urine volume, electrolytes excretion, pH and osmolality were measured at the end of the experiment (after 8h).

Results: Luteolin, at dose of 3mg/kg, was able to induce both diuretic and natriuretic effect in NTR and SHR groups, without interfering with urinary pH, K⁺ or Cl^- levels. While Ca²⁺ content remained unchanged in urine from luteolin-treated group of NTR, luteolin reduced Ca²⁺ excretion in urine from SHR. The treatment with HCTZ and amiloride intensified luteolin-induced diuresis and natriuresis, with an interesting potassium-sparing effect, in addition to an increase in urinary osmolality levels. Moreover, the diuretic and natriuretic action of luteolin was fully avoided in the presence of atropine, a non-selective muscarinic receptor antagonist.

Conclusions: This study revealed the diuretic and natriuretic effect of luteolin in normotensive and hypertensive rats. Our data also showed the involvement of muscarinic acetylcholine receptors for the renal effects of luteolin.

Keywords: Calcium; Digitoflavone; Diuresis; Flavonoid; Natriuresis.