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J Appl Physiol 87: 356-362, 1999;
8750-7587/99 $5.00
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Vol. 87, Issue 1, 356-362, July 1999

Differences in acute hypoxic pulmonary vasoresponsiveness between rat strains: role of endothelium

Gabriel Salameh1, Mallikharjuna R. Karamsetty1, Rod R. Warburton1, James R. Klinger1, Lo Chang Ou2, and Nicholas S. Hill1

1 Division of Pulmonary and Critical Care Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903; and 2 Department of Physiology, Dartmouth Medical Center, Hanover, New Hampshire 03756

Intact Madison (M) rats have greater pulmonary pressor responses to acute hypoxia than Hilltop (H) rats. We tested the hypothesis that the difference in pressor response is intrinsic to pulmonary arteries and that endothelium contributes to the difference. Pulmonary arteries precontracted with phenylephrine (10-7 M) from M rats had greater constrictor responses [hypoxic pulmonary vasoconstriction (HPV)] to acute hypoxia (0% O2) than those from H rats: 473 ± 30 vs. 394 ± 29 mg (P < 0.05). Removal of the endothelium or inhibition of nitric oxide (NO) synthase by Nomega -nitro-L-arginine (L-NA, 10-3 M) significantly blunted HPV in both strains. Inhibition of cyclooxygenase by meclofenamate (10-5 M) or blockade of endothelin type A and B receptors by BQ-610 (10-5 M) + BQ-788 (10-5 M), respectively, had no effect on HPV. Constrictor responses to phenylephrine, endothelin-1, and prostaglandin F2alpha were similar in pulmonary arteries from both strains. The relaxation response to ACh, an NO synthase stimulator, was significantly greater in M than in H rats (80 ± 3 vs. 62 ± 4%, P < 0.01), but there was no difference in response to sodium nitroprusside, an NO donor. L-NA potentiated phenylephrine-induced contraction to a greater extent in pulmonary arteries from M than from H rats. These findings indicate that at least part of the strain-related difference in acute HPV is attributable to differences in endothelial function, possibly related to differences in NO production.

nitric oxide synthase; cyclooxygenase; endothelin


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