The Effect Of Felodipine On Atherosclerosis And Kidney Protection

Objective To investigate the effect of calcium antagonist Felodipine on suppressing theproliferation of spontaneously hypertensive rat aortic smooth muscle cells and formation ofvascular smooth-derived foam cells, and the molecular mechanism of itsanti-atherosclerosis; To study the effects of felodipine and nifedipine on kidney protectionin SHRMethods VSMCs separated from spontaneously hypertensive rat aortic were cultured inoxLDL. Compared with control and Nifedipine respectively, the effect of Felodipine ofdifferent concentrations on suppressing the proliferation of spontaneously hypertensive rataortic smooth muscle cells was detected by cell count and water-soluble tetrazolium salt method;Oil Red staining was used to analyze different concentrations of felodipine on inhibiting theformation of vascular smooth-derived foam cells; The protein expression of p-ERK1/2andPPARγ was determined by western blot.30SHR male SHR at age16weeks were randomlyassigned into three groups: SHR control group, felodipine group, nifedipine group. Theblood pressure of rat was measured by the tail artery pressure every four weeks. Aftercarotid artery pressure recorded, the kindey was taken to calculat the renal hypertrophyindex. HE and MASSON coloration were used separately to detect the kindey morphologyand the renal fibrosis. Results VSMCs were formed after12h exposing to oxLDL. Cell count and water-solubletetrazolium salt method showed that Felodipine can inhibit the proliferation of rat vascular smoothmuscle cells in a dose-dependent manner (p <0.05); Oil Red staining method demonstrated thatFelodipine can inhibit the formation of foam cells in a dose-dependent manner (p <0.05). Western Blotresults showed that Felodipine prevented the oxLDL-stimulated phosphorylation of p42/44MARK andinduced PPARγ and ABCA1(p <0.05). At4week tail arterial pressure in SHR group was muchhigher than Felodipine group and Nifedipine group(P＜0.05); At the end of the experiment,carotid arterial pressure in SHR group was also much higher than Felodipine group andNifedipine group (P＜0.05); Compared with SHR control group, HE coloration results infilodipine and nifedipine groups was less obvious; Compared with SHR control group,MASSON coloration results in filodipine and nifedipine groups showed that renal fibrosiswas less obvious.Conclusion Felodipine could significantly inhibit proliferation and formation ofox-LDL-induced foam cells, with inhibition of ERK1/2signaling pathway and activationof PPARγ signaling pathway. Felodipine and nifedipine can successfully inhibit renalfibrosis.