Angiotensin II stimulates PGF(2 alpha) release in cultured neonatal rat ventricular myocytes via L-type calcium channels

Angiotensin II (Ang II) has been shown to cause Prostaglandin F-2 alpha (PG F(2 alpha)) release in neonatal rat ventricular myocytes and smooth muscle cells. In these cells, Ang II has also been shown to regulate growth. We us ed neonatal rat ventricular myocytes to investigate the role of calcium in maintenance of Ang II-induced PGF(2 alpha) release. The amount of PGF(2 alp ha) produced was determined by radioimmunoassay. Ang II-induced PGF(2 alpha ) release. Pretreatment of neonatal rat ventricular myocytes with different doses (10(-8) M, 10(-7) M, 10(-6) M and 10(-5) M) of diltiazm (voltage-sen sitive L-type calcium channel blocker) produced significant inhibition in A ng II-induced PGF(2 alpha) release. Inhibition was first noted at 10(-8) M and was complete at 10(-6) M. Conversely, pretreatment of neonatal rat vent ricular myocytes with different doses (10(-8) M, 10(-7) M, 10(-6) M and 10( -5) M) of calcium channel blockers (conotoxin; voltage-sensitive N-type cal cium channel blocker or thapsigargin; intracellular calcium channel blocker ) produced no changes in Ang II-induced PGF(2 alpha) release. These results strongly suggest that Ang II-induced PGF(2 alpha) release in neonatal rat ventricular myocytes is maintained, at least in part, via increase in extra cellular calcium influx. (C) 2001 Harcourt Publishers Ltd.