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 (similar to 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 ([Sar(1),Ile(8)]-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 similar to 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.