In vivo treatment with endotoxin increases rat pulmonary vascular contractility despite NOS induction.
Pulmonary hypertension is a feature of clinical and experimental acute lung injury. Nitric oxide (NO) synthesis is increased in hyporesponsive systemic and pulmonary conductance arteries after endotoxin (LPS) injection in the rat. We examined the effects of NO synthase (NOS) induction by LPS on vascular reactivity of the isolated perfused rat lung (IPL) using the selective inducible (iNOS) inhibitor aminoguanidine (AG). Baseline pulmonary artery pressures (Ppa) were higher in the LPS compared with the sham-treated rats and were further increased only in the LPS-treated group by AG. Increased NOS activity in whole lung and the vasopressor effect of AG suggested that iNOS was active in pulmonary resistance vessels after LPS treatment. Vasoconstriction to hypoxia, angiotensin II (AII), and prostaglandin F2 alpha (PGF2 alpha) was enhanced or unchanged in LPS-treated rats despite NOS induction. Hence, iNOS activity counterbalances increased pulmonary vascular contractility in this model.
Griffiths
M J
MJ
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Curzen
N P
NP
Mitchell
J A
JA
Evans
T W
TW
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012477:Salmonella enteritidis; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D015237:Dinoprost; D019001:Nitric Oxide Synthase; C004479:pimagedine