AJP - Heart and Circulatory Physiology, Vol 263, Issue 4 1113-H1118, Copyright © 1992 by American Physiological Society
Effects of CD-349 and 8-BrcGMP on isoproterenol-induced relaxation in rabbit aorta precontracted with endothelin-1
N. Miyata, H. Yamaura, K. Tsuchida and S. Otomo
Research Center, Taisho Pharmaceutical, Saitama, Japan.
We investigated the effects of CD-349, a dihydropyridine derivative, on
isoproterenol (Iso)-induced relaxation in rabbit aorta precontracted with
endothelin-1 (ET-1). The Iso (10(-8)-10(-5) M)-induced relaxation responses
in rabbit aorta precontracted with 1-2 x 10(-7) M ET-1 were augmented by
pretreatment with CD-349 (10(-9)-10(-5) M) in a concentration-dependent
manner. The effects of CD-349 on Iso-induced relaxation of the aortic
strips precontracted with ET-1 were inhibited by treatment with methylene
blue (10(-5) M) and oxyhemoglobin (10(-5) M), whereas they were augmented
by treatment with N omega-nitro-L-arginine (10(-4) M). The Iso-induced
relaxation responses were also augmented by pretreatment with
8-Br-guanosine 3',5'-cyclic monophosphate (cGMP) (3 x 10(-6)-3 x 10(-4) M)
in a concentration-dependent manner. However, nifedipine (10(-5) M) and
nicardipine (10(-5) M) had no effect on Iso-induced relaxation responses of
the aortic strips precontracted with 10(-7) M ET-1. CD-349 also augmented
forskolin (10(-8)-10(-5) M)-induced relaxation responses of rabbit aorta in
a concentration-dependent manner. CD-349 (10(-7)-10(-5) M) increased the
levels of cGMP but not of adenosine 3',5'-cyclic monophosphate (cAMP) in a
concentration-dependent manner in rabbit aorta without endothelium. Both
CD-349 (10(-5) M) and 8-BrcGMP (3 x 10(-5) M) augmented the Iso-induced
elevations of cAMP in rabbit aorta without endothelium. These results
indicate that CD-349 and 8-BrcGMP can augment Iso-induced relaxation
responses by enhancing the accumulation of cAMP.
