Korean J Physiol Pharmacol.
1997 Aug;1(4):393-402.
Mechanisms underlying relaxations caused by angiotensin II and its
analogs in isolated rabbit mesenteric artery
- Affiliations
-
- 1Department of Pharmacology, College of Medicine, Pusan National University,
Pusan 602-739, Korea.
- 2Center for Biofunctional Molecules, Postech, Pohang.
- 3Korea Research Institute of Chemical Technology, Daejeon 305-606, Korea.
Abstract
-
In the present study, we characterized the angiotensin II (AII)-induced
relaxations in the phenylephrineprecontracted rabbit mesenteric
arteries with endothelium. 1) AII-induced relaxation was consistently
observed in the rabbit mesenteric arteries with and without
endothelium, but not in the aortic segment with endothelium. 2)
AII-induced endothelium-dependent relaxation was markedly inhibited by
Nw-nitro-L-arginine (L-NNA, 100 micrometer), methylene blue (10 micrometer) and
LY83583 (10 micrometer), respectively. 3) Inhibition of cyclooxygenase with
indomethacin (10 micrometer) strongly decreased the vasorelaxant response to
AII irrespective of the presence of endothelium. 4) 7-Ethoxyresorufin
(1 micrometer) and clotrimazole (1 micrometer), inhibitors of cytochrome
P-450-dependent arachidonic acid metabolism, greatly attenuated the
vasodilator response to All. 5) Carbacyclin, arachidonic acid and
prostaglandin F2alpha, (PGF2alpha) caused concentration-dependent
relaxations in the mesenteric artery with endothelium, which were
inhibited by L-NNA and methylene blue. 6) AII and PGF2alpha,
significantly stimulated cyclic GMP formation in the mesenteric
arteries with endothelium, which was inhibited by L-NNA and methylene
blue, respectively. 7) AII enhanced synthesis of PGF2a and 6-keto PGF1a
from the arterial segments with endothelium, which was inhibitable by
indomethacin, but not by L-NNA. In conclusion, the vasorelaxant
responses to AII of the rabbit mesenteric artery with endothelium are
subserved by arachidonic acid and its metabolites produced via
activation of cyclooxygenase and cytochrome P-450 enzyme as well as by
nitric oxide.