Effects of a new positive inotropic agent with a vasodilatory action, 5-methyl-6-(4-pyridyl)-2H-1,4-thiazin-3(4H)-one (ZSY-27), on calcium-movement and mechanical response in rabbit thoracic aorta.
The effects of 5-methyl-6-(4-pyridyl)-2H-1,4-thiazin-3(4H)-one (ZSY-27), a positive inotropic agent with a vasodilatory action, on a concentration-response curve of CaCl2 in the KCl-depolarized rabbit thoracic aorta and Ca-uptake by the microsomal fraction from the rabbit artery were tested. ZSY-27 (10(-5) - 10(-4) M) inhibited noncompetitively a concentration-response curve of CaCl2 in the KCl-depolarized preparation. Furthermore, ZSY-27 (10(-5) M) stimulated significantly Ca-uptake by the microsomal fraction in the presence of oxalate, as an indicator for Ca-uptake by the internal membrane, in every incubation time. However, it inhibited significantly that in the absence of oxalate, as an indicator for Ca-uptake by the plasma membrane-derived vesicle, after 6 min of incubation time. These results suggest that ZSY-27 stimulates Ca-uptake by the internal membranes and inhibits Ca-uptake by the plasma membrane-derived vesicles. Therefore, these effects of ZSY-27 are considered to be related to relaxation of vascular smooth muscle.
Yoshioka
K
K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Takayanagi
I
I
Koike
K
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D010070:Oxalates / Q000494:pharmacology; D019815:Oxalic Acid; D011817:Rabbits; D013843:Thiazines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D010070:Oxalates; D013843:Thiazines; D014665:Vasodilator Agents; C050142:ZSY 27; D019815:Oxalic Acid; D002118:Calcium