Differential role of endothelium-derived nitric oxide in the modulation of the systemic and pulmonary circulation in lambs.
We have studied the differential role of endothelium-derived nitric oxide (EDNO) in the regulation of the systemic and pulmonary circulations of the lamb. Hemodynamic effects of NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg i.v.), an inhibitor of NO synthesis, were determined in juvenile (6 +/- 1 weeks old) lambs, under conditions of basal and elevated vasomotor tone. Under basal conditions, L-NAME raised both systemic (SVR) and pulmonary vascular resistances (PVR) by 20-30% (increasing SVR from 0.318 +/- 0.013 to 0.385 +/- 0.015 mm Hg.min.ml-1.kg and PVR from 0.050 +/- 0.003 to 0.067 +/- 0.010 mm Hg.min.ml-1.kg). When tone was elevated in the pulmonary circulation with hypoxia (PVR was elevated by 60%, from 0.059 +/- 0.010 to 0.094 +/- 0.019 mm Hg.min.ml-1.kg), L-NAME treatment resulted in an augmented increase in PVR (PVR increased by greater than 50% to 0.140 +/- 0.024 mm Hg.min.ml-1.kg). However, when tone was elevated to a comparable degree in the systemic circulation with angiotensin infusion (SVR was elevated by 60%, from 0.432 +/- 0.065 to 0.065 to 0.634 +/- 0.113 mm Hg.min.ml-1.kg), the response to L-NAME was not augmented. Our data suggest that the role of EDNO in the modulation of the pulmonary circulation is dependent on the level of vasomotor tone, whereas its role in the systemic circulation is small and is independent of the level of vasomotor tone.
Hibler
S
S
Department of Pediatrics, Harbor UCLA Medical Center, UCLA School of Medicine, Torrance 90509, USA.
Toga
H
H
Raj
J U
JU
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001775:Blood Circulation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014666:Vasomotor System / Q000254:growth & development / Q000502:physiology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester