Role of extracellular signal-related kinases in the pathophysiology of vascular dysfunction in aging and hypertension

Abstract

Recent evidence suggests that extracellular signal-regulated kinase-1/2 (ERK 1/2) affect vascular tone. The present study examined the role of this enzyme in vascular control under physiological and pathological conditions. Using tissue bath technique, vascular responses were measured in terms of changes in isometric tension in aortic rings that were isolated from normotensive Wistar-Kyoto (WKY) rats and hypertensive spontaneously hypertensive rats (SHR) at different ages, 36-39 week old (adult group) and 72-75 week ROG DJHGJURXS ,QKLELWLRQRI(5. E\8 ȝ0 UHGXFHGSKHQ\OHSKULQH induced contraction in aortae. The inhibitory effect of U0126 on contraction was smaller in aged WKY rats compared to the other groups. While U0126 did not affect relaxation WRDFHW\OFKROLQH ȝ0 LQDGXOW:.< UDWV LWHQKDQFHGDFHW\OFKROLQH LQGXFHGUHOD[DWLRQ in aged WKY rats and in adult and aged SHR. The enhanced relaxation was abolished by / 1$0( DQLWULFR[LGHV\QWKDVHLQKLELWRU ȝ0 LQ:.<DQG6+5RIDOODJHJURXSV DQG UHGXFHGE\LQGRPHWKDFLQ DF\FORR[\JHQDVHLQKLELWRU ȝ0 LQDJHG:.< UDWV Therefore, our results indicate that ERK 1/2 contributes to the contraction induced by phenylephrine to a similar degree in adult rats. On the other hand, ERK 1/2 is activated in aged and hypertensive rats, leading to the suppression of nitric oxide-mediated relaxation. As such, ERK 1/2 appears to contribute to vascular dysfunction in aging and hypertension.