Angiotensin II activates a bumetanide sensitive increase in Rb-86(+) efflux in the rat heart.

We previously reported that al-adrenoceptor (AR) stimulation of the isolate d perfused rat heart increased the efflux of K-42(+) and the K+ analogue Rb -86(+). The main part of this increase was bumetanide sensitive, indicating an activation of the Na+/K+/2Cl(-) - cotransporter. The purpose of the pre sent study was to investigate the effects of angiotensin II (1-100 nmol/l) and the protein kinase C (PKC) activator PMA (phorbol-12-myristate-13-aceta te, 1-1000 nmol/l) on Rb-86(+) efflux from isolated rat hearts and to compa re the effects with the effect of the alpha (1)- AR agonist phenylephrine ( 30 mu mol/l) in the presence of a beta -AR antagonist. Phenylephrine increa sed the Rb-86(+) efflux rate by 47 +/- 4.1 % (n=5, p<0.001). Angiotensin II induced a maximal increase in Rb-86(+) efflux rate of 13 <plus/minus> 1.6 % (n=12, p<0.0001). The effect of angiotensin II was totally eliminated by bumetanide (50 <mu>mol/l). PMA decreased the Rb-86(+) efflux rate by 23 +/- 7.0 % (n=7, p=0.02) and this effect of PMA was not sensitive to bumetanide. Pre-treatment of the hearts with PMA for 30 min did not influence the resp onse to phenylephrine. In conclusion, angiotensin II stimulation, but not P KC activation by PMA increased the Rb-86(+) efflux rate in isolated rat hea rts, but the effect was smaller than that of alpha (1)- AR stimulation. The effect of angiotensin II was completely abolished by bumetanide indicating an activation of the Na+/K+/2Cl(-)-cotransporter.