Angiotensin II activates a bumetanide sensitive increase in 86RB+ efflux in the rat heart.
We previously reported that alpha-adrenoceptor (AR) stimulation of the isolated perfused rat heart increased the efflux of 42K+ and the K+ analogue 86Rb+. The main part of this increase was bumetanide sensitive, indicating an activation of the Na+/K+/2Cl- cotransporter. The purpose of the present 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-acetate, 1-1000 nmol/l) on 86Rb+ efflux from isolated rat hearts and to compare the effects with the effect of the alpha1- AR agonist phenylephrine (30 micromol/l) in the presence of a beta-AR antagonist. Phenylephrine increased the 86Rb+ efflux rate by 47+/-4.1% (n=5, p<0.001). Angiotensin II induced a maximal increase in 86Rb+ efflux rate of 13+/-1.6% (n=12, p<0.0001). The effect of angiotensin II was totally eliminated by bumetanide (50 micromol/l). PMA decreased the 86Rb+ 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 response to phenylephrine. In conclusion, angiotensin II stimulation, but not PKC activation by PMA increased the 86Rb+ efflux rate in isolated rat hearts, but the effect was smaller than that of alpha1- AR stimulation. The effect of angiotensin II was completely abolished by bumetanide indicating an activation of the Na+/K+/2Cl- -cotransporter.
Andersen
G O
GO
Department of Pharmacology, University of Oslo, Norway. g.o.andersen@labmed.uio.no
Enger
M
M
Skomedal
T
T
Osnes
J B
JB
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000187:drug effects*; D012414:Rubidium Radioisotopes / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D012414:Rubidium Radioisotopes; D002034:Bumetanide; D000804:Angiotensin II; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C