VDR stimulation improves outcome of isoprenaline-induced myocardial infarction in rats via down-regulation of cardiac inos gene expression

Coronary heart disease has been reported to become a leading cause of death by the end of this decade. Isoprenaline-induced myocardial infarction is a well-known model to study myocardial infarction which is characterized by inflammation and oxidative stress. Meanwhile, vitamin D has been reported to have anti-inflammatory and antioxidant effects. The present study has been designed to investigate the effect of vitamin D receptor stimulation by a vitamin D receptor agonist, paricalcitol, on the outcome of isoprenaline (ISO) induced myocardial infarction in rats. Forty rats were divided into four equal groups (n= 10) for a 4-week experimental period. The first group (C) consisted of normal rats, the second group: normal rats injected with paricalcitol (C+P) at a dose of 200ng/kg 3 times a week for four weeks, these rats were used as a positive control. The third group consisted of rats injected with isoprenaline at a dose of 100mg/kg for the last 2 successive days of the study period, and the fourth group, isoprenaline-injected rats pretreated with paricalcitol. The same injection protocols for PC and isoprenaline were followed in the 4th group. The results showed that the ISO group exhibited significant ECG changes, cardiac enzymes and a histopathological picture of myocardial infarction. Pretreatment with PC before ISO injection resulted in minimal changes in the heart evidenced by near normal ECG, cardiac enzymes and histopathology. The serum tumour necrosis factor-alpha, Interlukin-6, as well as cardiac malondialdehyde and nitrites were significantly higher in ISO-treated rats compared to normal rats. Similarly, the cardiac content of inducible nitric oxide synthase messenger RNA was significantly elevated in ISO-injected animals. However, these parameters in rats subjected to ISO injection pretreated with PC were not significantly different from their counterpart controls. In conclusion, VDR stimulation with paricalcitol appears to have a protective action against isoprenaline-induced myocardial infarction via exerting anti-inflammatory and antioxidant effects, together with the down-regulation of cardiac inducible nitric oxide synthase gene expression.