Nitric oxide further attenuates pulmonary hypertension in magnesium-treated piglets.
BACKGROUND
Persistent pulmonary hypertension of the newborn (PPHN) commonly appears as a complication of several pulmonary and non-pulmonary diseases. The hypoxia possibly inhibits Ca2+ +/- dependent K+ channels, thus resulting in membrane depolarization of pulmonary smooth muscle cells, which leads to the opening of Ca2+ channels and Ca2+ entry, resulting in contraction of the vascular smooth muscle. However, magnesium (Mg2+) is an antagonist of Ca2+. We studied the effect of magnesium sulfate on the treatment of hypoxia-induced pulmonary hypertension and compared to the site of action of nitric oxide (NO).


METHODS
Zero-day-old piglets were used in each experiment. The effects of Mg2+ were tested in each hypoxic, normoxic and hyperoxic states. Once the desired physical state was achieved, Mg2+ was administered at a dose of 100 mg/kg approximately every 10 min. In order to determine the exact mechanism of the Mg2+, Nw-nitro-l-arginine (LNNA), a NO synthase-inhibitor, was administered simultaneously with Mg2+ in some of the experiments.


RESULTS
There was a significant correlation between the percent reduction of the pulmonary arterial pressure (PAP) caused by magnesium and the level of oxygen (O2) present in the pulmonary artery. The greatest amount of reduction was seen in the hypoxic condition where the least amount of O2 is found. A further reduction in the PAP was seen when NO was given at the end of the Mg2+ trials. There was no significant reduction seen in the systemic arterial pressure.


CONCLUSIONS
Inhaled NO further reduced the PAP in piglets already treated with Mg2+.
Haas
Kelly Mullins
KM
Department of Pediatrics, Nagoya City University Medical School, Nagoya, Japan.
Suzuki
Satoshi
S
Yamaguchi
Nobuyuki
N
Kato
Ineko
I
Ban
Kyoko
K
Tanaka
Taihei
T
Fukuda
Sumio
S
Togari
Hajime
H
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D000860:Hypoxia / Q000150:complications; D016014:Linear Models; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D013552:Swine; D014665:Vasodilator Agents / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D009569:Nitric Oxide; D008278:Magnesium Sulfate