The interactions between UK-14304 and other vasoconstrictor agents were investigated using isolated canine mesenteric vascular rings mounted in tissue baths for the measurement of isometric contraction. In the mesenteric artery, exposure to UK-14304 caused a small contraction, producing 8% of the KCl maximal response. In the presence of either 20 mM KCl or 10(-9) M endothelin-1, which had small contractile effects, UK-14304 produced a biphasic concentration-response curve; 10(-7) M rauwolscine inhibited the responses to low concentrations of UK-14304 and 10(-7) M prazosin blocked the responses to high concentrations of UK-14304. In the presence of 10(-8) M Bay K 8644, UK-14304 elicited a monophasic concentration-dependent contraction that was antagonized by 10(-7) M prazosin, not by 10(-7) M rauwolscine. In the mesenteric vein, UK-14304 elicited concentration-dependent contractions, producing 63% of the KCl maximal response. The lower part of the biphasic concentration-response curve was inhibited by 10(-7) M rauwolscine and the upper part of the curve was antagonized by 10(-7) M prazosin. The presence in the medium of 20 mM KCl, 10(-11) M endothelin-1 or 10(-9) M Bay K 8644, which increased resting tension less than 10% of the KCl maximal response, markedly enhanced the responses to UK-14304 primarily at concentrations lower than 10(-6) M. The enhancement of responses were prazosin (10(-7) M)-resistant and rauwolscine (10(-7) M)-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)