Strain differences in pulmonary hypertensive response to monocrotaline alkaloid and the beneficial effect of oral magnesium treatment.
Magnesium therapy has been shown, by us, to attenuate monocrotaline (MCT)-induced pulmonary artery hypertension (PAH), right ventricular hypertrophy and pathological changes in the pulmonary vasculature in 75% of Sprague-Dawley rats. We studied Wistar rats to determine if there was a strain difference in response to MCT and magnesium therapy. Wistar rats were given 60 mg/kg of MCT and studied 3 weeks later, following a protocol similar to that for Sprague-Dawley rats. There was 100% mortality in Wistar rats weighing less than 230 g. The mortality rate in Sprague-Dawley rats of a similar weight range was significantly less (15%). With 40 mg/kg of MCT, Wistar rats developed pulmonary hypertension and right ventricular hypertrophy comparable to those seen in Sprague-Dawley rats administered 60 mg/kg MCT. The percent weight gain over a 3-week period was significantly higher in the Wistar control group than that in the Sprague-Dawley controls (61 vs. 39%; p less than 0.05). Oral magnesium therapy (magnesium aspartate HCl) attenuated pulmonary hypertension and right ventricular hypertrophy in 100% of the Wistar rats studied. A group of Sprague-Dawley rats was given 40 mg/kg of MCT and studied 3 weeks later. PAH and right ventricular hypertrophy in this group were not significantly different from the rats of the same strain injected with the higher dose of MCT. In conclusion, faster growing rats (Wistar) appear to be more sensitive to MCT. Both strains show a significant attenuation of cardiopulmonary changes induced by MCT when treated with oral magnesium.
Mathew
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Department of Physiology, SUNY Health Sciences Center, Brooklyn.
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D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000188:drug therapy; D008274:Magnesium / Q000627:therapeutic use*; D008297:Male; D016686:Monocrotaline; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D015430:Weight Gain / Q000187:drug effects
D011763:Pyrrolizidine Alkaloids; D016686:Monocrotaline; D008274:Magnesium