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

Intact Madison (M) rats have greater pulmonary presser responses to acute h ypoxia than Hilltop (H) rats. We tested the hypothesis that the difference in presser response is intrinsic to pulmonary arteries and that endothelium contributes to the difference. Pulmonary arteries precontracted with pheny lephrine (10(-7) M) from M rats had greater constrictor responses [hypoxic pulmonary vasoconstriction (HPV)] to acute hypoxia (0% O-2) than those from H rats: 473 +/- 30 vs. 394 +/- 29 mg (P < 0.05). Removal of the endotheliu m or inhibition of nitric oxide (NO) synthase by N-omega-nitro-L-arginine ( L-NA, 10(-3) M) significantly blunted HPV in both strains. Inhibition of cy clooxygenase by meclofenamate (10(-5) M) or blockade of endothelin type A a nd B receptors by BQ-610 (10(-5) M) + BQ-788 (10(-5) M), respectively, had no effect on HPV. Constrictor responses to phenylephrine, endothelin-l, and prostaglandin Fz, were similar in pulmonary arteries from both strains. Th e 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 w as no difference in response to sodium nitroprusside, an NO donor. L-NA pot entiated phenylephrine-induced contraction to a greater extent in pulmonary arteries from M than from H rats. These findings indicate that at; least p art of the strain-related difference in acute HPV is attributable to differ ences in endothelial function, possibly related to differences in NO produc tion.