Effect of inhaled nitric oxide in endothelin-1-induced pulmonary hypertension.
The interaction of two vasoactive substances, the vasoidilator nitric oxide (NO) and the complex-acting peptide endothelin-1 (ET-1), may help explain the pathophysiology of pulmonary hypertension, an important part of many pulmonary disorders in neonates. To understand better the interactions of inhaled NO and ET-1, we investigated the effects of ET-1 infusions with and without inhaled NO in two groups of piglets, one group pretreated with L-nitro-arginine methylester (L-NAME) and the other not pretreated. Inhaled NO (60 ppm) was administered during infusion of 1.0 microgram/kg or 2.5 micrograms/kg of ET-1. In animals not pretreated with L-NAME, the increase in PVR and in SVR induced by either dose of ET-1 was not reduced with administration of NO. The increase in systemic vascular resistance with ET-1 was greater (mean increase of 50% above baseline with 1.0 microgram/kg ET-1 and 100% with 2.5 micrograms/kg ET-1 by 5 min) than the increase in PVR, but the PVR/SVR ratio did not change during ET-1 administration. In contrast, animals pretreated with L-NAME did demonstrate inhibition of ET-1-induced increase in PVR with NO. No differences in effects on SVR were noted. We conclude that ET-1-induced increases in PVR are not diminished by 60 ppm of inhaled NO unless there has been inhibition of endogenous NO production.
Truog
W E
WE
Section of Neonatal/Perinatal Medicine, Children's Mercy Hospital, Kansas City, MO 64108-9898, USA. wtruog@cmh.edu
Norberg
M
M
Thibeault
D W
DW
D000280:Administration, Inhalation; D000818:Animals; D004347:Drug Interactions; D019332:Endothelin-1; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D008168:Lung / Q000098:blood supply; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013552:Swine; D014655:Vascular Resistance
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester