Mechanisms of bradykinin-mediated dilation in newborn piglet pulmonary conducting and resistance vessels.
Bradykinin (BK) is a potent dilator of the perinatal pulmonary circulation. We investigated segmental differences in BK-induced dilation in newborn pig large conducting pulmonary artery and vein rings and in pressurized pulmonary resistance arteries (PRA). In conducting pulmonary arteries and veins, BK-induced relaxation is abolished by endothelial disruption and by inhibition of nitric oxide (NO) synthase with nitro-L-arginine (L-NA). In PRA, two-thirds of the dilation response is L-NA insensitive. Charybdotoxin plus apamin and depolarization with KCl abolish the L-NA-insensitive dilations, findings that implicate the release of endothelium-derived hyperpolarizing factor (EDHF). However, endothelium-disrupted PRA retain the ability to dilate to BK but not to ACh or A-23187. In endothelium-disrupted PRA, dilation was inhibited by charybdotoxin. Thus in PRA, BK elicits dilation by multiple and duplicative signaling pathways. Release of NO and EDHF contributes to the response in endothelium-intact PRA; in endothelium-disrupted PRA, dilation occurs by direct activation of vascular smooth muscle calcium-dependent potassium channels. Redundant signaling pathways mediating pulmonary dilation to BK may be required to assure a smooth transition to extrauterine life.
Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1081, USA. jaschner@wfubmc.edu
Judy L
JL
Aschner
Thuy K
TK
Smith
Nora
N
Kovacs
Joaquim M B
JM
Pinheiro
Mamta
M
Fuloria
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001685:Biological Factors / Q000502:physiology; D001808:Blood Vessels / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014655:Vascular Resistance; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D015221:Potassium Channels; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003577:Cytochrome P-450 Enzyme System; D001920:Bradykinin