{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:03:36Z","timestamp":1791263016364,"version":"4.1.0"},"reference-count":51,"publisher":"American Physiological Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"<jats:p> Myogenic tone is an intrinsic property of the vasculature that contributes to blood pressure control and tissue perfusion. Earlier investigations assigned a key role in myogenic tone to phospholipase C (PLC) and its products, inositol 1,4,5-trisphosphate (IP<jats:sub>3<\/jats:sub>) and diacylglycerol (DAG). Here, we used the PLC inhibitor, U-73122, and two other, specific inhibitors of PLC subtypes (PI-PLC and PC-PLC) to delineate the role of PLC in myogenic tone of pressurized murine mesenteric arteries. U-73122 inhibited depolarization-induced contractions (high external K<jats:sup>+<\/jats:sup> concentration), thus confirming reports of nonspecific actions of U-73122 and its limited utility for studies of myogenic tone. Edelfosine, a specific inhibitor of PI-PLC, did not affect depolarization-induced contractions but modulated myogenic tone. Because PI-PLC produces IP<jats:sub>3<\/jats:sub>, we investigated the effect of blocking IP<jats:sub>3<\/jats:sub> receptor-mediated Ca<jats:sup>2+<\/jats:sup> release on myogenic tone. Incubation of arteries with xestospongin C did not affect tone, consistent with the virtual absence of Ca<jats:sup>2+<\/jats:sup> waves in arteries with myogenic tone. D-609, an inhibitor of PC-PLC and sphingomyelin synthase, strongly inhibited myogenic tone and had no effect on depolarization-induced contraction. D-609 appeared to act by lowering cytoplasmic Ca<jats:sup>2+<\/jats:sup> concentration to levels below those that activate contraction. Importantly, incubation of pressurized arteries with a membrane-permeable analog of DAG induced vasoconstriction. The results therefore mandate a reexamination of the signaling pathways activated by the Bayliss mechanism. Our results suggest that PI-PLC and IP<jats:sub>3<\/jats:sub> are not required in maintaining myogenic tone, but DAG, produced by PC-PLC and\/or SM synthase, is likely through multiple mechanisms to increase Ca<jats:sup>2+<\/jats:sup> entry and promote vasoconstriction. <\/jats:p>","DOI":"10.1152\/ajpheart.00594.2014","type":"journal-article","created":{"date-parts":[[2015,4,18]],"date-time":"2015-04-18T02:41:52Z","timestamp":1429324912000},"page":"H1517-H1524","source":"Crossref","is-referenced-by-count":17,"title":["PC-PLC\/sphingomyelin synthase activity plays a central role in the development of myogenic tone in murine resistance arteries"],"prefix":"10.1152","volume":"308","author":[{"given":"Joseph R. 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