Vascular Hypertrophy‐Associated Hypertension of Profilin1 Transgenic Mouse Model led to Functional Remodeling of Vasculature

Abstract

Hypertrophy is accompanied with hypertension and till now there is no direct approach to assess the response of these hypertrophic blood vessels towards the vasoactive agents which is important for the treatment of hypertension. We have developed a novel transgenic mouse model by over‐expressing the cDNA of human profilin 1 in the blood vessels of transgenic mice. Our results showed significant increases in F/G‐actin ratio and in the medial thickness of profilin 1 mice (P<0.05). Western blotting confirmed the activation of the hypertrophic signaling in the VSMCs of profilin 1 mice such as Phospho‐ERK1/2 and JNK (512.3% and 371.4% respectively, P<0.05). There was also increase in ROCK II kinase and Rho‐GTPase activities in mesenteric arteries of profilin 1 mice (P<0.05). Our results also showed elevation of blood pressure in profilin1 mice starting at age 6 month (~ 25 mmHg, P<0.05). Functional analyses of mesenteric arteries toward the vasoactive drugs were assessed using wire‐myograph. The results showed significant increase in the vascular responses of profilin1 mesenteric arteries towards phenylephrine, Angiotensin II and Cytochalasin, but, significant decrease in response towards sodium nitrite. In conclusion, vascular hypertrophy of blood vessels led to functional remodeling of the mesenteric arteries as demonstrated by changing the responses towards the vocative agent.