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Effects of a selective nitric oxide synthase inhibitor on endotoxin-induced alteration in hypoxic pulmonary vasoconstriction in sheep.
J Cardiovasc Pharmacol. 2003 Oct; 42(4):521-6.JC

Abstract

It has been suggested that overproduction of nitric oxide (NO) by nitric oxide synthase (NOS) contributes to blunted hypoxic pulmonary vasoconstriction (HPV) during endotoxemia. We investigated the effect of a selective inducible NOS (iNOS) inhibitor, ONO-1714, on the loss of HPV during endotoxemia in awake sheep to clarify the role of iNOS. We prepared 11 intubated, awake sheep with hemodynamic monitoring. Hypoxic challenges (FiO2; 12%) were performed before, and 5, 24, 48, 72 hours after endotoxin (1 microg/kg) infusion for 15 minutes. Pulmonary artery (Ppa) and left atrial pressure (Pla) were continuously measured and cardiac output (CO) was measured by the thermodilution method. Pulmonary vascular resistance (PVR) was calculated by (Ppa - Pla)/CO. The percent change in PVR (%PVR) before (pre-PVR) and after (post-PVR) hypoxia was calculated as (post-PVR - pre-PVR)/pre-HPV x 100. ONO-1714 (0.1 mg/kg, n=5, Exp 1) or normal saline (n=6, Exp 2) was administered 5 hours before hypoxic challenge every day. ONO-1714 did not affect the baseline pulmonary hemodynamics before endotoxin administration. % PVR before and after hypoxic exposure was significantly decreased 5 hours after endotoxin administration and gradually improved to baseline at 72 hours. Treatment with iNOS inhibition significantly restored % HPV (24.7+/-5.5% in Exp1 versus -3.1+/-3.6% in Exp 2, 5 hours, 25.3+/-2.5% in Exp 1 versus 7.7+/-2.2% in Exp 2, 24 hours). It is suggested that inducible nitric oxide is related to pulmonary vascular hyporesponsiveness to hypoxia during endotoxemia in sheep.

Authors+Show Affiliations

First Department of Medicine, Shinshu University School of Medicine, Masumoto, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14508238

Citation

Ogasawara, Hitoshi, et al. "Effects of a Selective Nitric Oxide Synthase Inhibitor On Endotoxin-induced Alteration in Hypoxic Pulmonary Vasoconstriction in Sheep." Journal of Cardiovascular Pharmacology, vol. 42, no. 4, 2003, pp. 521-6.
Ogasawara H, Koizumi T, Yamamoto H, et al. Effects of a selective nitric oxide synthase inhibitor on endotoxin-induced alteration in hypoxic pulmonary vasoconstriction in sheep. J Cardiovasc Pharmacol. 2003;42(4):521-6.
Ogasawara, H., Koizumi, T., Yamamoto, H., & Kubo, K. (2003). Effects of a selective nitric oxide synthase inhibitor on endotoxin-induced alteration in hypoxic pulmonary vasoconstriction in sheep. Journal of Cardiovascular Pharmacology, 42(4), 521-6.
Ogasawara H, et al. Effects of a Selective Nitric Oxide Synthase Inhibitor On Endotoxin-induced Alteration in Hypoxic Pulmonary Vasoconstriction in Sheep. J Cardiovasc Pharmacol. 2003;42(4):521-6. PubMed PMID: 14508238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of a selective nitric oxide synthase inhibitor on endotoxin-induced alteration in hypoxic pulmonary vasoconstriction in sheep. AU - Ogasawara,Hitoshi, AU - Koizumi,Tomonobu, AU - Yamamoto,Hiroshi, AU - Kubo,Keishi, PY - 2003/9/26/pubmed PY - 2004/3/6/medline PY - 2003/9/26/entrez SP - 521 EP - 6 JF - Journal of cardiovascular pharmacology JO - J Cardiovasc Pharmacol VL - 42 IS - 4 N2 - It has been suggested that overproduction of nitric oxide (NO) by nitric oxide synthase (NOS) contributes to blunted hypoxic pulmonary vasoconstriction (HPV) during endotoxemia. We investigated the effect of a selective inducible NOS (iNOS) inhibitor, ONO-1714, on the loss of HPV during endotoxemia in awake sheep to clarify the role of iNOS. We prepared 11 intubated, awake sheep with hemodynamic monitoring. Hypoxic challenges (FiO2; 12%) were performed before, and 5, 24, 48, 72 hours after endotoxin (1 microg/kg) infusion for 15 minutes. Pulmonary artery (Ppa) and left atrial pressure (Pla) were continuously measured and cardiac output (CO) was measured by the thermodilution method. Pulmonary vascular resistance (PVR) was calculated by (Ppa - Pla)/CO. The percent change in PVR (%PVR) before (pre-PVR) and after (post-PVR) hypoxia was calculated as (post-PVR - pre-PVR)/pre-HPV x 100. ONO-1714 (0.1 mg/kg, n=5, Exp 1) or normal saline (n=6, Exp 2) was administered 5 hours before hypoxic challenge every day. ONO-1714 did not affect the baseline pulmonary hemodynamics before endotoxin administration. % PVR before and after hypoxic exposure was significantly decreased 5 hours after endotoxin administration and gradually improved to baseline at 72 hours. Treatment with iNOS inhibition significantly restored % HPV (24.7+/-5.5% in Exp1 versus -3.1+/-3.6% in Exp 2, 5 hours, 25.3+/-2.5% in Exp 1 versus 7.7+/-2.2% in Exp 2, 24 hours). It is suggested that inducible nitric oxide is related to pulmonary vascular hyporesponsiveness to hypoxia during endotoxemia in sheep. SN - 0160-2446 UR - https://www.unboundmedicine.com/medline/citation/14508238/Effects_of_a_selective_nitric_oxide_synthase_inhibitor_on_endotoxin_induced_alteration_in_hypoxic_pulmonary_vasoconstriction_in_sheep_ L2 - https://doi.org/10.1097/00005344-200310000-00010 DB - PRIME DP - Unbound Medicine ER -