title: Effect of endogenous and exogenous nitric oxide on calcium sparks as targets for vasodilation in rat cerebral artery.
abstract: The potent vasodilator nitric oxide (NO), produced mainly by the endothelium, acts through a BK(Ca)-dependent mechanism to increase the frequency of calcium sparks (Ca(2+) sparks) in myocyte isolated from rat cerebral arteries. Our present aim has been to assess the role of endogenous and exogenous NO on the Ca(2+) sparks through ryanodine-sensitive channels in the sarcoplasmic reticulum of an intact artery. Calcium sparks, detected with fluo-4 and laser scanning confocal microscopy, were examined in isolated pressurized rat posterior cerebral arteries with (intact) and without endothelium (denuded). Addition of the NO donor, DEA-NONOate (N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine), did not change the amplitude and frequency of Ca(2+) sparks in the intact artery. However, inhibition of nitric oxide synthase with N-omega-nitro-L-arginine or removal of endothelium reduced Ca(2+) sparks frequency by about 50%. Under these conditions (i.e., absence of endogenous NO production), DEA-NONOate, increased Ca(2+) spark frequency 3- to 4-fold. These results suggest that endothelial NO modulates local Ca(2+) release events in the arterial smooth muscle and that this mechanism may contribute to the actions of nitrovasodilators.
authors.affiliation: Department of Cell Biology, University of Calabria, 87036 Arcavacata di Rende, CS, Italy. m.mandala@unical.it <m.mandala@unical.it>
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mandalà
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Heppner
authors.forename: Adrian D
authors.initials: AD
authors.lastname: Bonev
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D014664:Vasodilation
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D009569:Nitric Oxide; D002118:Calcium