title: Flosequinan, a vasodilator with a novel mechanism of action.
abstract: 1. The mechanism of action of flosequinan was investigated in ferret aortic smooth muscle by the simultaneous measurement of aequorin luminescence and isometric force. 2. The control calcium-force curve was obtained by plotting the calibrated aequorin luminescence against the force from potassium-depolarized muscles. Flosequinan relaxed potassium-depolarized muscles by causing parallel changes in [Ca2+]i and force with no shift in the control [Ca2+]i-force relationship. 3. The [Ca2+]i-force relationship in the presence of a maximally effective concentration of phenylephrine was significantly shifted to the left of that for the control, potassium-depolarized muscle. Flosequinan relaxed the phenylephrine-contracted muscle by causing a large decrease in force with only a minimal decrease in [Ca2+]i, resulting in an apparent rightward shift of the [Ca2+]i-force relationship, toward the control curve. 4. In comparison, sodium nitroprusside caused relaxation of either the potassium- or phenylephrine-induced contraction solely by a decrease in [Ca2+]i with no shift in either calcium-force relationship. 5. Milrinone caused no significant rightward shift of the calcium-force relationship during phenylephrine- or potassium-induced contractions, but when milrinone was added in the absence of vasoconstrictors, relaxation was obtained with no significant decrease in [Ca2+]i. 6. Flosequinan appears to differ in mechanism of action from both nitroprusside and milrinone. It relaxes depolarization-mediated contractions solely by decreasing [Ca2+]i but also appears to be capable of reversing the apparent calcium sensitizing action of phenylephrine.
authors.affiliation: Charles Dana Research Institute, Harvard-Thorndike Laboratory, Department of Medicine, Harvard Medical School, Beth Israel Hospital, Boston, MA 02215.
authors.forename: M S
authors.initials: MS
authors.lastname: Resnick
authors.forename: L A
authors.initials: LA
authors.lastname: Maitland
authors.forename: K G
authors.initials: KG
authors.lastname: Morgan
mesh_terms: D000331:Aequorin / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D005289:Ferrets; D066298:In Vitro Techniques; D008297:Male; D020105:Milrinone; D009119:Muscle Contraction / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D011728:Pyridones; D011804:Quinolines; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000331:Aequorin; C047316:flosequinan; D020105:Milrinone; D011188:Potassium; D002118:Calcium