169P Granada Congress and Exhibitions Centre
6th European Congress of Pharmacology (EPHAR 2012)

 

 

Age-dependent changes of β 2 -adrenoceptor function in the rabbit heart

J Perez-Fornieles, A Galindo-Tovar, E Escudero, ML Vargas, AJ Kaumann. University of Murcia, Department of Pharmacology. 30100, Spain

 

It has been suggested that β2-adrenoceptor (β2AR) stimulation is the main mechanism by which sinoatrial heart rate is increased in adult New Zealand white rabbits (Barbuti et al. 2007). We have studied the age-dependent function of sinoatrial and ventricular β2ARs in mixed breed Chinchilla and California rabbits. Spontaneously beating right atria (RA), left atrial trabeculae (LA) and right ventricular papillary muscles (PM), were dissected from the hearts of new-born (1-3 days), juvenile (1-2 months) and adult (1-2.5 years) rabbits. PM and LA were paced at 1Hz. The tissues were pretreated 90 min with phenoxybenzamine (5μM) to block α-adrenoceptors and neuronal uptake of adrenaline as previously described (Kaumann et al. 2009). β2ARs were activated with adrenaline in the presence of the β1AR-selective antagonist CGP20712A (300nM) and maximum stimulation of β1AR+β2AR assessed with isoprenaline (200μM). Fractional values (f) of the maximum effects of adrenaline through each β1AR and β2AR, f1+f2=1, and pD2s were estimated from concentration-effect curves (Table 1). High adrenaline concentrations surmounted the blockade of β1AR by CGP20712A. CGP20712A-resistant chronotropic and inotropic effects of adrenaline, blockable by the β2AR antagonist ICI118551 (25-50nM), were detected in RA and PM respectively, but not in LA of the 3 age groups.

Table 1

f2 (x100) and pD2 values of adrenaline for the sinoatrial node in right atria (RA) and right ventricular papillary muscles (PM). Data are mean±S.E.M. n = number of rabbits.

N e w b o r n J u v e n i l e s A d u l t s
RA n PM n RA n PM n RA n PM n
f2 55±12 8 41±12 10 8.3±2.9 10 8.3±2.4 15 14.1±4.0 10 9.8±2.8 12
pD2 7.47±0.16 7.67±0.14 7.43±0.24 7.79±0.20 7.26±0.13 7.57±0.24

Conclusions: Adrenaline increases sinoatrial beating rate and ventricular force similarly through β1ARs and β2ARs in new-born rabbit hearts but the contribution of β2ARs decays markedly in juvenile and adult rabbit hearts.The inotropic effects of adrenaline on rabbit left atria are entirely mediated through β1ARs, regardless of age.

Barbuti A, Terragni B, Brioschi C, DiFrancesco D (2007) J Mol Cell Cardiol 42:71-78.

Kaumann AJ, Galindo-Tovar A, Escudero E, Vargas ML (2009) Naunyn-Schmiedeberg´s Arch Pharmacol 380:421-430.