ANGIOTENSIN-II-INDUCED PHOSPHOINOSITIDE PRODUCTION AND ATRIAL-NATRIURETIC-PEPTIDE RELEASE IN RAT ATRIAL TISSUE

The effect of angiotensin II (Ang II) on inositol phosphate (IP) produ ction and atrial natriuretic peptide (ANP) release was studied in slic ed rat atrial tissue. The ability of Ang II (10(-7) M) to stimulate IP accumulation was detected after 1 min of incubation, and the maximal increase was observed at 5 min. In (2-H-3) inositol-labeled atrial tis sue, Ang II induced the formation of (2-H-3) inositol monophosphate (I P1) in a dose-dependent manner. The effect of Ang II (10(-7) M) on IP1 was prevented by losartan (10(-7) M) but was not affected by PD123319 (10(-7) M). Similar effects were observed on Ang II-induced ANP relea se in the presence of these antagonists. The mechanism of ANP liberati on induced by this peptide was independent of cyclic adenosine monopho sphate (cAMP) and regulated by nitric oxide (NO). The role of Ca2+ in the effect of Ang II was tested by 1,2-bis (o-aminophenoxy)-ethane-N,N ,N ',N '- tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM; 10(- 5) M), a chelator of intracellular Ca2+ that prevented the release of ANP by Ang LI stimulation We concluded that Ang II induced IP producti on and ANP release through AT(1) receptors. Stimulation of ANP release by Ang II was dependent on intracellular Ca2+.