PMID- 10960077 OWN - NLM STAT- MEDLINE DCOM- 20001103 LR - 20181113 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 131 IP - 1 DP - 2000 Sep TI - Mechanisms of the thapsigargin-induced Ca(2+) entry in in situ endothelial cells of the porcine aortic valve and the endothelium-dependent relaxation in the porcine coronary artery. PG - 115-23 AB - The mechanisms of the thapsigargin (TG)-induced capacitative Ca(2+) entry in in situ endothelial cells and its role in the regulation of arterial tone were investigated using front-surface fluorimetry and fura-2-loaded strips of porcine aortic valve and coronary artery. In the presence of extracellular Ca(2+), TG induced an initial rapid and a subsequent sustained elevation of cytosolic Ca(2+) concentration ([Ca(2+)](i)) in valvular strips. In the absence of extracellular Ca(2+), TG induced only a transient increase in [Ca(2+)](i). The TG-induced sustained elevation of [Ca(2+)](i) in endothelial cells was inhibited completely by 1 mM Ni(2+) and partly by 10 microM econazole and 30 microM ML-9, but not by 900 ng ml(-1) pertussis toxin or 100 microM wortmannin. Therefore, cytochrome P450 and protein phosphorylation are suggested to be involved in the TG-induced Ca(2+) influx in in situ endothelial cells. TG induced an endothelium-dependent large relaxation consisting of an initial and a late sustained relaxation in coronary arterial strip precontracted with U46619 (a thromboxane A2 analogue). Indomethacin alone had no effect, while indomethacin plus N(omega)-nitro-L-arginine (L-NOARG) markedly inhibited the sustained phase and slightly inhibited the initial phase of the TG-induced relaxation. TG induced a smaller but sustained relaxation during the 40 mM K(+)-induced precontraction than that seen during the U46619-induced precontraction. This relaxation was completely abolished by the pretreatment with indomethacin plus L-NOARG. In conclusion, both nitric oxide (NO) and endothelium-derived hyperpolarizing factor were suggested to mediate the TG-induced relaxation, while NO plays a major role in the sustained relaxation. The TG-induced sustained [Ca(2+)](i) elevation in endothelial cells was thus suggested to be mainly linked to the sustained production of NO. FAU - Kuroiwa-Matsumoto, M AU - Kuroiwa-Matsumoto M AD - Department of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. FAU - Hirano, K AU - Hirano K FAU - Ahmed, A AU - Ahmed A FAU - Kawasaki, J AU - Kawasaki J FAU - Nishimura, J AU - Nishimura J FAU - Kanaide, H AU - Kanaide H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Biological Factors) RN - 0 (endothelium-dependent hyperpolarization factor) RN - 2149-70-4 (Nitroarginine) RN - 31C4KY9ESH (Nitric Oxide) RN - 67526-95-8 (Thapsigargin) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - RWP5GA015D (Potassium) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Aortic Valve/*drug effects/metabolism MH - Biological Factors/physiology MH - Calcium/*metabolism MH - Coronary Vessels/*drug effects/physiology MH - Endothelium, Vascular/*drug effects/physiology MH - In Vitro Techniques MH - Nitric Oxide/physiology MH - Nitric Oxide Synthase/physiology MH - Nitroarginine/pharmacology MH - Potassium/pharmacology MH - Swine MH - Thapsigargin/*pharmacology MH - Vasoconstriction/drug effects MH - Vasodilation/*drug effects PMC - PMC1572304 EDAT- 2000/08/26 11:00 MHDA- 2001/02/28 10:01 PMCR- 2001/09/01 CRDT- 2000/08/26 11:00 PHST- 2000/08/26 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/08/26 11:00 [entrez] PHST- 2001/09/01 00:00 [pmc-release] AID - 0703548 [pii] AID - 10.1038/sj.bjp.0703548 [doi] PST - ppublish SO - Br J Pharmacol. 2000 Sep;131(1):115-23. doi: 10.1038/sj.bjp.0703548.