Phytoestrogens Enhance the Vascular Actions of the Endocannabinoid Anandamide in Mesenteric Beds of Female Rats

Roxana N Peroni,Isabel Neuman,Tamara Abramoff,Edda Adler-Graschinsky,Ernesto J Podestá

doi:10.1155/2012/647856

Abstract

In rat isolated mesenteric beds that were contracted with NA as an in vitro model of the vascular adrenergic hyperactivity that usually precedes the onset of primary hypertension, the oral administration (3 daily doses) of either 10 mg/kg genistein or 20 mg/kg daidzein potentiated the anandamide-induced reduction of contractility to NA in female but not in male rats. Oral treatment with phytoestrogens also restored the vascular effects of anandamide as well as the mesenteric content of calcitonin gene-related peptide (CGRP) that were reduced after ovariectomy. The enhancement of anandamide effects caused by phytoestrogens was prevented by the concomitant administration of the estrogen receptor antagonist fulvestrant (2.5 mg/kg, s.c., 3 daily doses). It is concluded that, in the vasculature of female rats, phytoestrogens produced an estrogen-receptor-dependent enhancement of the anandamide-vascular actions that involves the modulation of CGRP levels and appears to be relevant whenever an adrenergic hyperactivity occurs.

Highlights

Endocannabinoids contribute to reduce vascular contractility under pathological conditions where vascular responsiveness is altered
A 3-day treatment with the soy-derived phytoestrogen daidzein did not modify the anandamide-induced reduction of contractile responses when administered at a dose of 10 mg/kg to either female (Figure 2(a)) or male rats (Figure 2(b)) but did significantly increase the anandamide effects in mesenteries isolated from female rats when dose was scaled up to 20 mg/kg (Figure 2(c))
The present study shows that oral administration of the soyderived phytoestrogens genistein and daidzein daily during days enhanced the decrease in the contractile responses to NA induced by anandamide in mesenteric arteries isolated from female but not from male rats

Summary

Introduction

Endocannabinoids contribute to reduce vascular contractility under pathological conditions where vascular responsiveness is altered. Compounds that selectively modulate the action as well as the levels of endocannabinoids represent templates for potential new therapeutic strategies [1]. In this sense, the exogenous administration of the endocannabinoid anandamide is known to induce the decrease of blood pressure in spontaneously hypertensive rats [2] as well as in Wistar rats fed with a high-salt diet [3]. This potent vasodilator peptide is released, at least in part, as a consequence of the activation of the transient receptor potential vanilloid type 1 (TRPV1) by anandamide [7]

Methods

Results

Conclusion