The effects of the vitamin D receptor activator paricalcitol on left ventricular remodeling. Importance of renin.

Background: Heart failure (HF) is known to be a major medical problem in the Western world with increasing incidence and prevalence. Current treatment is not sufficient yet, as cure is still absent. One of the novel concepts in intervening pathophysiology in HF includes influencing regulators of gene transcription, with the vitamin D receptor as gene regulator of particular importance for cardiovascular disease and HF. Over activity of the renin-angiotensin-system (RAS) is considered as one of underlying mechanisms which causes symptoms of HF. Therefore, regulation of RAS would be a step forward in finding a cure. Paricalcitol, a vitamin D receptor activator, may indirectly inhibit left ventricle remodeling in hypertrophic hearts by suppressing renin expression, and may therefore offer a novel mechanism to control the RAS. Methods: C57/BL6 mice were treated with 10 mg/kg/day isoproterenol, 1 mg/kg/day angiotensin II or saline (0.9% NaCl) via a subcutaneously located mini-pump for 14 days. Half of the groups received 300 ng/kg/day paricalcitol, 3 times a week via intraperitioneally injections, while other half received vehicle. After 14 days treatment had ended and mice were echoed and sacrificed. Results: Treatment with isoproterenol increases LV/TL & HW/TL-ratio (p<0.05), and so does angiotensin II. Plasma renin activity (PRA) turns out to dependent on treatment: high levels were seen in isoproterenol treated mice, while angiotensin II treated mice showed depressed serum levels of PRA. Injection of paricalcitol results in significantly lower PRA and PTH levels (p