Dynamic Ca2+ signalling in rat arterial smooth muscle cells under the control of local renin‐angiotensin system

1 We visualized the changes in intracellular Ca2+ concentration ([Ca2+]i), using fluo‐3 as an indicator, in individual smooth muscle cells within intact rat tail artery preparations. 2 On average in about 45 % of the vascular smooth muscle cells we found spontaneous Ca2+ waves and oscillations (≈0.13 Hz), which we refer to here as Ca2+ ripples because the peak amplitude of [Ca2+]i was about one‐seventh of that of Ca2+ oscillations evoked by noradrenaline. 3 We also found another pattern of spontaneous Ca2+ transients often in groups of two to three cells. They were rarely observed and are referred to as Ca2+ flashes because their peak amplitude was nearly twice as large as that in noradrenaline‐evoked responses. 4 Sympathetic nerve activity was not considered responsible for the Ca2+ ripples, and they were abolished by inhibitors of either the Ca2+ pump in the sarcoplasmic reticulum (cyclopiazonic acid) or phospholipase C (U‐73122). 5 Both angiotensin antagonists ([Sar1,Ile8]‐angiotensin II and losartan) and an angiotensin converting enzyme inhibitor (captopril) inhibited the Ca2+ ripples. 6 The extracellular Ca2+‐dependent tension borne by unstimulated arterial rings was reduced by the angiotensin antagonist by ≈50 %. 7 These results indicate that the Ca2+ ripples are generated via inositol 1,4,5‐trisphosphate‐induced Ca2+ release from the intracellular Ca2+ stores in response to locally produced angiotensin II, which contributes to the maintenance of vascular tone.