Heme oxygenase does not contribute to control of basal vascular tone in isolated blood-perfused rat lung.
BACKGROUND
Vasoconstriction in pulmonary ischemia-reperfusion injury may involve dysfunction of the physiologic vasodilation of pulmonary arteries. Little is known of the relative importance of heme oxygenase (HO)/carbon monoxide (CO)-dependent vs nitric oxide synthase (NOS)/nitric oxide (NO)-dependent vasodilation of the pulmonary vasculature. We evaluated the significance of HO function on basal pulmonary vascular resistance (PVR) and compared it with the function of NOS.


METHODS
Using an isolated blood-perfusion model, lungs of Lewis rats were assigned to 3 groups (n = 6/group). After stabilization, either an inhibitor of HO (tin-protoporphyrin-9 [SnPP-9]) or an inhibitor of NOS (NG-nitro-L-arginine methylester [L-NAME]) was added to the perfusate (50 micromol/liter and 1 mmol/liter as the final concentration, respectively). Lungs receiving saline served as controls. Gas exchange, hemodynamic and respiratory functions and the levels of cyclic 3',5'-guanosine monophosphate (cGMP) in the perfusate were measured.


RESULTS
Inhibition of NOS by L-NAME resulted in a significant (p < 0.01) increase in PVR (DeltaPVR: 0.110 +/- 0.012 cm H(2)O/ml. min) within 5 minutes. In contrast, PVR was minimally affected by SnPP-9 (DeltaPVR: 0.005 +/- 0.005 cm H(2)O/ml. min), which was comparable to control lungs (DeltaPVR: 0.012 +/- 0.005 cm H(2)O/ml. min). The level of cGMP in the perfusate 5 minutes after drug application was markedly, but not significantly, lower in the L-NAME group (1.67 +/- 0.74 nmol/liter) when compared with controls (2.69 +/- 0.89 nmol/liter) and SnPP-9-treated lungs (2.65 +/- 0.66 nmol/liter).


CONCLUSIONS
NOS but not HO contributes to the control of basal vascular tone in the rat lung.
Nakamura
Takayuki
T
Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany. tnakamur@kuhp.kyoto-u.ac.ip
Vollmar
Brigitte
B
Menger
Michael D
MD
Inui
Kenji
K
Wada
Hiromi
H
Schäfers
Hans-Joachim
HJ
D000818:Animals; D006152:Cyclic GMP / Q000032:analysis; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000502:physiology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D014655:Vascular Resistance / Q000502:physiology*
D008665:Metalloporphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester