EFFECTS OF ANGIOTENSIN-II ON CYTOSOLIC CA LCIUM RELEASES IN ISOLATED VENTRICULAR MYOCYTES FROM ADULT NORMAL AND HYPERTENSIVE RATS

This study investigated the effects of angiotensin II (Ang II) (10(-9) M to 10(-7) M) on calcium releases in ventricular myocytes from norma l and renal hypertensive adult rats (Goldblatt 2K-1C). Newly, isolated myocytes were loaded with fluorescent indo-1/AM and studied at rest o r under electrical stimulation. The variation of the ratio of indo-1 e mission (405 nm/480 nm) was taken as a measure of cytosolic calcium va riations. Five parameters were investigated from each peak systolic in do-I ratio before and after Ang II addition : amplitude variation, dur ation with analysis of a rise time and a fall time, and frequency of s pontaneous calcium releases. Following changes were observed: in unsti mulated myocytes exhibiting spontaneous contractile activity, increase in frequency of calcium transients, at 10(-7) M, in normal cells (+ 1 57 +/- 27 % ; p < 0.01) and whatever Ang II concentration in hypertrop hied cells (+ 79 +/- 31 % ; p < 0.01 ; + 82 +/- 25 %, p < 0.01 ; + 285 +/- 50 %, p < 0.01 a 10(-9) M, 10(-8) M, 10(-7) M) ; in stimulated my ocytes, prolongation of the duration of calcium transients explained b y the occurrence of calcium releases during fall time. In addition, 50 % of myocytes exhibited spontaneous releases of calcium in the inters timulus interval. Increase in calcium transients duration was statisti cally significant, whatever Ang II concentration in hypertrophied cell s (+ 36 +/- 20 %, p < 0.05 ; + 39 +/- 18 %, p < 0.01 ; + 77 +/- 34 %, p < 0.01 a 10(-9) M, 10(-8) M, 10(-7) M) and only at 10(-7) M in norma l cells (+ 68 +/- 22 % p < 0.01). Similar results were observed in fal l time. Thus, both in normal and hypertrophied myocytes, angiotensin I I induced occurrence of calcium releases with an increased sensitivy o f hypertrophied cells to angiotensin II. This occurrence of calcium re leases is known as a possible cause of arrhythmias, termed ''triggered activity''.