title: Effects of synthetic analogues of poly-APS on contractile response of porcine coronary arteries.
abstract: APS12-2 and APS3 are synthetic analogues of polymeric alkylpyridinium salts (poly-APS) isolated from the marine sponge Reniera sarai. The aim of the present study was to determine the possible direct contractile effects of these two synthetic molecules on coronary arteries, in order partly to explain hemodynamic and cardiotoxic effects of APS12-2 previously observed in in vivo studies and to reveal possible adverse effects on the organism in the case of their clinical use. In contrast to APS3, APS12-2 caused a concentration-dependent vascular smooth muscle contraction of isolated porcine coronary ring preparations in a concentration-range from 1.36 to 13.60μM. Lanthanum chloride (5mM) and verapamil (10μM) completely abolished the APS12-2 evoked contraction of the coronary rings. Pre-incubation with indomethacin (10μM) had no effect on the contractile responses of coronary ring preparations. These results indicate that APS12-2 contracts vascular smooth muscle in a concentration-dependent manner, due to an increase of Ca(2+) influx through the voltage-gated Ca(2+) channels. Our data show for the first time that APS12-2 induces concentration-dependent contraction of coronary ring preparations, which may contribute to the cardiotoxic effects of APS12-2, in addition to hyperkalemia.
authors.affiliation: Institute of Physiology, Pharmacology and Toxicology, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia.
authors.forename: Marjana
authors.initials: M
authors.lastname: Grandič
authors.forename: Blanka Premrov
authors.initials: BP
authors.lastname: Bajuk
authors.forename: Kristina
authors.initials: K
authors.lastname: Sepčić
authors.forename: Marinka Drobnič
authors.initials: MD
authors.lastname: Košorok
authors.forename: Robert
authors.initials: R
authors.lastname: Frangež
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000737:chemistry / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D011108:Polymers; D011726:Pyridinium Compounds; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C115254:poly-APS; D014700:Verapamil; D002118:Calcium