Stimulation of the ADRB3 Adrenergic Receptor Induces Relaxation of Human Placental Arteries: Influence of Preeclampsia1

Abstract

Preeclampsia, which complicates 3-8% of pregnancies, is one of the leading causes of neonatal morbidity and mortality. Its pathophysiology remains unclear. The aim of the present study was to investigate the presence and the role of beta2- and beta2-adrenergic receptors (ADRB2 and ADRB3, respectively) in human placental arteries and to assess the influence of preeclampsia on ADRB responsiveness. SR 59119A, salbutamol, and isoproterenol (ADRB3, ADRB2, and nonselective ADRB agonists, respectively) induced a concentration-dependent relaxation of placental artery rings obtained from women with uncomplicated or preeclamptic pregnancies. SR 59119A-induced relaxation was unaffected by the blockade of ADRB1 and ADRB2 by 0.1 microM propranolol but was significantly decreased by the blockade of ADRB1, ADRB2, and ADRB3 by 10 microM propranolol. Both SR 59119A and salbutamol were associated with a significant increase in cAMP production that was significantly inhibited by pretreatment with 0.1 microM propranolol only for salbutamol. SR 59119A-induced relaxation (E(max) = 28% +/- 5% vs. 45% +/- 4%, respectively) and cAMP production (2.7 +/- 0.5 vs. 4.9 +/- 0.4 pmol/mg of protein, respectively; P < 0.01) were decreased in arteries obtained from preeclamptic compared to normotensive women. Both ADRB2 and ADRB3 transcripts were expressed at the same level between arteries from normotensive and preeclamptic women. Western blot analysis, however, revealed a decreased expression of the ADRB3 immunoreactive protein in arteries from preeclamptic compared to normotensive women. We suggest the presence of functional ADRB2 and ADRB3 in human placental arteries. Even if preeclampsia is associated with an impairment of the ADRB3 responsiveness, ADRB3 agonists may have future pharmaceutical implications in the management of pregnancy-related disorders.

Cellular and subcellular distributions of β1- and β2-Adrenoceptors in the CA1 and CA3 regions of the rat hippocampus

“…These antibodies have been previously used by other authors to detect the expression of ␤1-and ␤2-ARs (Naren et al, 2003;Liang and Fishman, 2004;Rouget et al, 2006). In the present study, we performed both positive and negative control experi- ments and demonstrated the specificity of the ␤1-and ␤2-AR antibodies.…”

β-Adrenoceptor Subtype Expression in Human Placenta and Umbilical Arteries in Normal and Preeclamptic Pregnancies

“…Our findings confirm and extend those of Rouget and coworkers, who recently showed that the presence of preeclampsia did not influence the mRNA expression levels of β 2 -AR and β 3 -AR in placental vessels isolated from the chorionic plate (20). However, a difference was observed between the study by Rouget and colleagues (20) and the present study in relation to β 3 -AR protein expression.…”

Different β‐adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels

“…Interestingly, recent evidences suggest that Adrb1 appear to be mainly responsible for vasorelaxation in mouse (Chruscinski et al, 2001) and rat mesenteric resistance arteries (MRA) (Briones et al, 2005), and mediate smooth muscle hyperpolarization in rat MRA (Garland et al, 2011). In addition, the participation of Adrb3 in the vasorelaxant response has also been documented in some blood vessels, such as the rat carotid artery (Oriowo, 1994), rat (Sooch and Marshall, 1997) and canine (Tagaya et al, 1999) pulmonary artery, the human internal mammary (Rozec et al, 2005) and placental (Rouget et al, 2006) arteries, and also in coronary microarteries (Dessy et al, 2004). Nevertheless, there have been conflicting reports on Adrb3 involvement in vasodilator responses in rat aorta.…”