Beneficial effects of magnesium nitrate on disease severity in male rats with monocrotaline-induced pulmonary hypertension.

Inorganic nitrates and magnesium salts are effective in the treatment of pulmonary hypertension (PH). Here, we examined whether magnesium nitrate, which belongs to both categories, has a vasorelaxant effect on pulmonary arteries and protects against PH. In organ chamber experiments with isolated rat pulmonary arteries, high concentrations of magnesium nitrate (3 and 10 mM) produced weak relaxation, and phenylephrine-induced contraction was attenuated in the presence of 3 mM magnesium nitrate. Exposure to magnesium nitrate (3 mM) did not affect acetylcholine-induced relaxation. In rats with monocrotaline (MCT)-induced PH, supplementation of drinking water with magnesium nitrate (3 and 10 mM) for 2 weeks from 2 weeks after MCT injection (60 mg/kg, s.c.) alleviated right ventricular systolic pressure elevation, regardless of the dose. High-dose magnesium nitrate also suppressed pulmonary arterial medial thickening. Treatment with magnesium nitrate did not reduce right ventricular hypertrophy. Low-dose magnesium nitrate tended to increase plasma nitrate levels, which increased significantly at a higher dose. High-dose magnesium nitrate also increased plasma magnesium levels. These findings suggest that magnesium nitrate has antispasmodic effects on pulmonary arteries and is effective in halting the progression of PH, demonstrating its usefulness in managing PH.