Differences in acute hypoxic pulmonary vasoresponsiveness between rat strains: role of endothelium.
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% O(2)) 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 N(omega)-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 F(2alpha) 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.
Salameh
G
G
Division of Pulmonary and Critical Care Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA.
Karamsetty
M R
MR
Warburton
R R
RR
Klinger
J R
JR
Ou
L C
LC
Hill
N S
NS
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014661:Vasoconstriction / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010880:Piperidines; C087220:BQ 610; D019335:Nitroarginine; D009569:Nitric Oxide; C086539:BQ 788; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase