ANGIOTENSIN-I MODULATES CA TRANSPORT-SYSTEMS IN THE RAT-HEART THROUGHANGIOTENSIN-II

The objective of this study was to determine the effect of angiotensin I (Ang I) treatment in vivo on two major Ca-transport systems-the L-t ype voltage dependent calcium channel (L-VDCC) and the Na/Ca exchanger in rat heart. For our experiments we used four groups of rats, treate d differently with saline, Ang I, the ACE inhibitor enalapril and/or c ombination of both for 6 days, every 24 h. We observed an increase in the activity, and also in mRNA expression of the Na/Ca exchanger, afte r repeated administration of Ang I in vivo. The maximal binding capaci ty of Ca-antagonist PN 200-110, which binds to the alpha(1) subunit of the L-VDCC was elevated from 0.8-1.85 pg/mg protein. mRNA expression of the voltage-dependent calcium channels of L-type system was also up regulated by Ang I administration, but not when enalapril was applied simultaneously with Ang I. These results demonstrate that in vivo appl ication of the Ang I significantly modulates not only the activity, bu t also expression of the Na/Ca exchanger and the L-VDCC in rat hearts through angiotensin II (Ang II). Since in the in vitro experiments on the isolated cardiomyocytes, Ang II (100 nM) increased the calcium upt ake after depolarization, and the AT(1) receptor agonist losartan prev ented this increase, we assume that this regulation might involve the AT(1) receptors. (C) 1997 Academic Press Limited.