Evidence against endogenously released adenosine as modulator of the pressor response to hypoxia in isolated rat lungs.
Unlike other vascular beds, lung vessels constrict when exposed to hypoxia. However, a marked difference has been noticed as regards the elicitability of hypoxic pulmonary vasoconstriction (HPV) in vivo as compared to in vitro models, like a preparation of isolated rat lungs; in the latter, HPV cannot be evoked from the onset of perfusion, but might be triggered gradually by repeated hypoxic challenges. The formation of adenosine, a potent dilator of most vascular beds, is enhanced during conditions of hypoxia or ischemia. Our hypothesis therefore was that pulmonary vasoconstriction was initially antagonized by tissue-adenosine accumulating during the circulatory arrest necessary for lung isolation, and then, gradually invigorated along with the elimination of adenosine during periods of perfusion with normally oxygenated blood. In a first series of isolated rat lungs, we studied release of adenosine in connection with the third and the sixth hypoxic challenges. Although the vascular responses were of significantly different size, there was no sign of increased adenosine formation during any of the two provocations, as assessed by release of its more stable metabolites hypoxanthine, xanthine and uric acid. In a series of tissue preparations taken at the height of a fully developed hypoxic pressor response and immediately frozen, we could not find significant changes in tissue level of adenosine, hypoxanthine and inosine as compared to controls that had never been exposed to hypoxic challenges. Further, we found no correlation between the size of pressor responses and concentrations of adenosine and its metabolites, in either blood or in lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Jolin
A
A
Department of Anesthesiology, University of Tromsø, Norway.
Kjaeve
J
J
Helset
E
E
Tollåli
T
T
Sollevi
A
A
Bjertnaes
L
L
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000502:physiology*
D000241:Adenosine