The influence of beta-adrenergic activation on noradrenergic alpha(1) activation of rabbit afferent arterioles

The aim of the present investigation was to examine the effect of beta -adr energic stimulation on smooth muscle calcium concentration ([Ca2+](i)) in r esting conditions and after administration of norepinephrine (NE) to stimul ate alpha -adrenoceptors in isolated rabbit afferent arterioles loaded with the calcium-sensitive fluorescent probe fura-2. [Ca2+](i) was evaluated in the proximal and distal parts of the arterioles. NE (4x10(-7) M) increased [Ca2+](i) in both these regions. The alpha (1)-adrenoceptor antagonist pra zosin (10(-7) M) totally abolished the NE-induced increase in [Ca2+](i) whi le the alpha (2)-adrenoceptor antagonist yohimbine (5x10(-7) M) had no infl uence on the response to NE. When beta -adrenoceptors were stimulated, usin g isoproterenol (10(-7) M), the NE-induced increase in [Ca2+](i) was signif icantly lower in both regions. Activation of beta -adrenoceptors with isopr oterenol did not affect the [Ca2+](i) increase in response to depolarizatio n with K+. Since beta -adrenoceptor stimulation raises the smooth muscle ce ll levels of cAMP, an adenylate cyclase stimulator, forskolin (10(-5) M) wa s administered prior to NE application. This maneuver also blunted the incr ease in [Ca2+](i) in both regions. We conclude that the calcium response to NE in the isolated rabbit afferent arteriole is mediated by an alpha (1)-a drenoceptor. beta -Adrenoceptor stimulation and forskolin blunt the increas e in [Ca2+](i) induced by NE stimulation, indicating that cAMP counteracts the NE-induced activation of alpha (1)-adrenoceptors.