The Effect of Selective Antihypertensive drugs on the Vascular Remodeling‐associated Hypertension: Insights from a Profilin1 Transgenic Mouse Model

Hypertension represents a major risk factor for cardiovascular diseases. We have developed a novel transgenic mouse model by overexpressing the cDNA of human profilin1 in the blood vessels of transgenic mice which led to vascular hypertrophy and hypertension. We assessed the effects of losartan, amlodipine or atenolol on vascular hypertrophy‐associated hypertension, by treating the profilin1 transgenic mice for 4 weeks. Our myograph results showed improvement in the contraction response towards phenylephrine and in the relaxation response towards acetylcholine and sodium nitrite in losartan‐ and amlodipine‐treated profilin1 mice. Western blot analyses using mesenteric arteries of lasortan and amlodipine‐treated profilin1 mice showed significant decreases in their signaling respectively as follows: the expression of α1 integrin (104% and 93%) and β1 integrin (116% and 109%); p‐ERK1/2 (149% and 130%) and p‐JNK (171% and 137%); the phospho‐myosin light chain20 (p‐MLC20) (117% and 150%) and the ROCKII expression (125% and 180). Conversely, there were significant increases in the eNOS expression (82% and 80%) and activation (p‐eNOS) (78 and 76%). On the other hand, atenololtreated profilin1 mice showed no significant change in all measured parameters. In conclusion, Profilin1 gene may represent a new therapeutic target in the treatment of vascular hypertrophy‐associated hypertension.