Spasmolytic effect of magnesium sulfate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.
BACKGROUND
Magnesium (Mg2+) has relaxant effects on histamine-induced bronchoconstriction. In addition, Mg2+ has been reported to reduce vascular smooth muscle tone and be clinically useful for treatment of persistent pulmonary hypertension of the newborn. In this study, we evaluated the relaxant effect of Mg2+ on serotonin (5HT)-induced bronchoconstriction and pulmonary hypertension.


METHODS
Seven mongrel dogs were anesthetized with pentobarbital (30 mg x kg(-1) + 2 mg x kg(-1) x h(-1)) and paralyzed by pancuronium (0.2 mg x kg(-1) x h(-1)). Bronchoconstriction and pulmonary hypertension were elicited with 5HT (10 microg x kg(-1) + 1 mg x kg(-1) x h(-1)). Airway caliber was evaluated by changes in bronchial cross-sectional area (BCA) of the 3rd bronchial bifurcation measured by a fiberoptic bronchoscope method as previously reported. Pulmonary hypertension was assessed by changes in pulmonary vascular resistance (PVR). The BCA and PVR were expressed as per cent of the basal level. Thirty minutes after start of 5HT infusion, magnesium sulfate (MgSO4): 0 (saline), 1, 10, 100 and 1000 micromol x kg(-1) was given i.v.. Arterial blood was also collected to measure plasma level of Mg2+ and catecholamines.


RESULTS
5HT increased %PVR to 163+/-25% and decreased % BCA by 39.2+/-4.5%. Plasma level of Mg2+ following MgSO4 1000 micromol x kg(-1) i.v. exceeded its toxic level. The ED50s of MgSO4 (dose producing 50% relaxation of maximal constriction) was 47.8 micromol x kg(-1) and 1.09 mmol x kg(-1) for pulmonary hypertension and bronchoconstriction, respectively. The ratio of %PVR to %SVR was about 1.0 after MgSO4 0-100 micromol x kg(-1) i.v., although the ratio significantly increased after 1000 micromol x kg(-1) i.v..


CONCLUSIONS
In dogs, 5HT-induced pulmonary hypertension but not bronchoconstriction was significantly reduced by an iv bolus of MgSO4, resulting in a plasma concentration within the assumed therapeutic level.
Yoshioka
H
H
Department of Anesthesiology, University of Hirosaki School of Medicine, Japan.
Hirota
K
K
Sato
T
T
Hashimoto
Y
Y
Ishihara
H
H
Matsuki
A
A
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D008278:Magnesium Sulfate / Q000097:blood / Q000494:pharmacology*; D009129:Muscle Tonus / Q000187:drug effects; D010276:Parasympatholytics / Q000097:blood / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects; D012701:Serotonin
D002395:Catecholamines; D010276:Parasympatholytics; D012701:Serotonin; D008278:Magnesium Sulfate