Pressure loading-induced mitogen-activated protein kinase activation is enhanced in prehypertensive spontaneously hypertensive rat vasculature

The vascular structural remodeling function may be altered in spontaneously hypertensive rats (SHR). To examine this possibility, we examined whether pressure loading-induced activation of mitogen-activated protein kinases (MAPKs) is enhanced in the vasculature of prehypertensive SHR and whether angiotensin and endothelin systems in the vasculature are involved in the enhanced MAPK activation in SHR vasculature. Male 4-week-old SHR and age-matched Wistar Kyoto rats (WKY) were used. Aortae were perfused with Tyrode solution. Increases in perfusion pressure caused an increase in p42/p44 MAPK activity in WKY and SHR aortae. MAPK activities in SHR aortae perfused at 100 and 200 mmHg were greater than those of WKY. The enhanced MAPK activation in SHR aortae was greatly inhibited by the angiotensin receptor antagonist losartan but minimally by the endothelin receptor antagonist BQ123. Cyclic stretching of aortic vascular smooth muscle cells from SHR and WKY aortae produced an increase in p42/p44 MAPK activity. The stretch-induced MAPK activation was almost the same in both cells. These results indicate that pressure loading-induced MAPK activation is enhanced in aortae from prehypertensive SHR. It appears that the enhancement of MAPK activation results partly from enhanced angiotensin system in SHR aortae.