Vascular mitogen-activated protein kinase activity is enhanced via angiotensin system in spontaneously hypertensive rats

The vascular structural remodeling function may be altered in genetically h ypertensive animals, spontaneously hypertensive rats (SHR). To examine this possibility, we measured the activity of mitogen-activated protein (MAP) k inases, enzymes believed to be involved in the pathway for cell proliferati on, in rat aorta strips, and examined whether the endothelium removal-induc ed MAP kinase activation function is altered in SHR and whether vascular an giotensin and endothelin systems are responsible for the alteration of MAP kinase activation in SHR. Male 4-week-old SHR and age-matched Wistar Kyoto rats (WKY) supplied by Charles River Japan were used. Endothelium-denuded a orta strips were incubated at 37 degrees C in medium. MAP kinase activity a fter incubation was time-dependently increased in strips from SHR and WKY. MAP kinase activation was greater in SHR than in WKY aorta strips. Similarl y, MAP kinase activation was enhanced in aorta strips from 4-week-old SHR a nd stroke prone SHR supplied by the Diseases Model Cooperative Research Ass ociation (Kyoto, Japan). In aorta strips from SHR and WKY, the angiotensin receptor antagonist, losartan, and the endothelin receptor antagonist, cycl e (D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-trytophyl)(BQ123), caused c oncentration-dependent inhibition of MAP kinase activation. The losartan-in duced but not BQ123-induced inhibition of MAP kinase activation was greater in SHR than in WKY aorta strips. Angiotensin II caused a concentration-dep endent increase in MAP kinase activity and the angiotensin II-induced MAP k inase activation was greater in SHR than in WKY aorta strips. These results indicate that endothelium removal-induced MAP kinase activation is enhance d in aorta strips from young SHR, suggesting that vascular structural remod eling function may be enhanced in SHR. It appears that the enhancement of M AP kinase activation results, at least in part, from enhanced function of v ascular angiotensin system in SHR. (C) 1999 Elsevier Science B.V. All right s reserved.