Effect of single oral administration of YM598, a novel selective endothelin ETA receptor antagonist, on blood pressure in normotensive and hypertensive rats.
We investigated the effect of YM598, a selective endothelin ETA receptor antagonist, on blood pressure (BP) in normotensive rats (NTR), spontaneously hypertensive rats (SHR) and Dahl salt-sensitive hypertensive rats (Dahl-SS). We also examined the concomitant effect of YM598 with the L-type Ca2+ channel antagonist nifedipine on BP. Single oral administration of YM598 did not affect BP in NTR and SHR. In Dahl-SS, in contrast, YM598 slightly, but not significantly, reduced BP. Concomitant administration of YM598 with nifedipine at doses inducing slight hypotension on respective single administrations resulted in a stronger hypotensive effect than single administration of either compound alone. However, the magnitude of the concomitant hypotensive effect demonstrated only a simple additive effect of the two compounds. These results indicate that YM598 did cause slight hypotensive effects in some types of hypertension. These results also indicate the possibility of additive, but not synergic, hypotensive effects on concomitant administration of ET receptor antagonist and an L-type Ca2+ channel antagonist.
Yuyama
Hironori
H
Institute for Drug Discovery Research, Applied Pharmacology Research, Pharmacology Laboratories, Yamanouchi Pharmaceutical Co., Ltd., 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. yuyama@yamanouchi.co.jp
Sonoda
Rie
R
Shibasaki
Kumiko
K
Fujimori
Akira
A
Sudoh
Katsumi
K
Sasamata
Masao
M
Miyata
Keiji
K
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004334:Drug Administration Schedule; D065130:Endothelin A Receptor Antagonists; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage*; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage*
D065130:Endothelin A Receptor Antagonists; C449179:N-(6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl)-2-phenylethenesulfonamide; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D013449:Sulfonamides