Pharmacological characterization of EK112, a new combined angiotensin II and thromboxane A(2) receptor antagonist.
The pharmacological characterization of EK112, a new combined angiotensin II and thromboxane A(2) receptor blocking agent, was examined in this study. EK112 was found to be a angiotensin II receptor antagonist, as revealed by its competitive antagonism of angiotensin II-induced smooth muscle contraction (pA(2) value of 7. 63 +/- 0.14) in rabbit aorta. It also had an angiotensin II blocking action in guinea pig ileum (pA(2) value of 7.87 +/- 0.67). Additionally, EK112 also possessed thromboxane A(2) receptor blocking activity, since it competitively antagonized aortic contractile responses elicited by U46619 and PGF(2alpha)(pK(B) values of 6.67 +/- 0.09 and 6.24 +/- 0.09, respectively) in rat. In contrast, EK112 did not affect the contractile responses to many other receptor agonists. EK112 did not mimic that of the angiotensin-converting enzyme (ACE) inhibitor, captopril, to enhance the muscle contraction elicited by bradykinin in guinea pig ileum, suggesting that EK112 did not inhibit ACE. Neither cyclic AMP nor cyclic GMP content in rat aortic rings was changed by EK112. These data demonstrate that EK112 is a selective antagonist of angiotensin II > thromboxane A(2) thromboxane A(2) receptor.
Hwang
T L
TL
Pharmacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Sect. 1, Taipei, Taiwan.
Yeh
Y A
YA
Chern
J W
JW
Teng
C M
CM
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D002216:Captopril