AJP - Heart and Circulatory Physiology, Vol 253, Issue 5 1074-H1082, Copyright © 1987 by American Physiological Society
Mechanisms of endothelium-dependent vascular smooth muscle relaxation elicited by bradykinin and VIP
L. J. Ignarro, R. E. Byrns, G. M. Buga and K. S. Wood
Department of Pharmacology, University of California School of Medicine, Los Angeles 90024.
The objective of this study was to elucidate the mechanisms by which
bradykinin and vasoactive intestinal polypeptide (VIP) relax bovine
intrapulmonary artery and bradykinin, but not VIP, relaxes intrapulmonary
vein. Bradykinin and VIP elicited entirely endothelium-dependent relaxation
of phenylephrine-precontracted arterial rings, and this was associated with
arterial accumulation of both guanosine 3',5'-cyclic monophosphate (cGMP)
and adenosine 3',5'-cyclic monophosphate (cAMP). Bradykinin, but not VIP,
relaxed precontracted venous rings and increased cGMP, but not cAMP levels,
by endothelium-dependent mechanisms. Neither arteries nor veins relaxed in
response to substance P, thrombin, bombesin, arginine vasopressin, or
angiotensin II. Methylene blue or indomethacin each partially antagonized,
whereas both, when together, abolished arterial relaxant responses to
bradykinin and VIP. Methylene blue or indomethacin, respectively, abolished
arterial cGMP or cAMP accumulation elicited by bradykinin and VIP. Venous
relaxation and cGMP accumulation elicited by bradykinin was abolished by
methylene blue but was unaltered by indomethacin. Thus bradykinin and VIP
relaxed bovine intrapulmonary artery by endothelium-dependent mechanisms
involving the actions of cGMP and cAMP whose formation may be stimulated by
endothelium-derived relaxing factor and prostacyclin, respectively. In
contrast, bradykinin relaxed intrapulmonary vein by endothelium-dependent
mechanisms involving only cGMP.
