The effects of aging on relaxation in aortic smooth muscle : role of myosin phosphatase and rho kinase

Abstract

It is well documented that the risk of vascular diseases increases with age. Furthermore, it is known that the myosin phosphate and Rho kinase enzymes are integral in regulating Ca 2+ sensitivity in vascular smooth muscle. Therefore, the goals of this study were to evaluate the roles of myosin phosphates and Rho kinase in regulating relaxation and to test whether these enzymes are involved in age-related changes in vascular smooth muscle. the aortas of male rats, ages 6 months and 2 years, were isolated, attached to a force transducer, and placed in water-jacketed bath chambers. All of the tissues were contracted with norephinephrine (NE) and then treated with either Calyculin A, a myosin phosphatase inhibitor, or Y-27632, a Rho kinase inhibitor. The tissues treated with Calyculin A were relaxed with sodium nitroprusside (SNP), whereas Y-27632 alone induced relaxation in that group. Total relaxation and the rate of relaxation were compared between aged and young tissues for each treatment group. Calyculin A significantly reduced the total percent relaxation in both you and aged tissues compared to their controls. In the control groups, the young tissue relaxed at a significantly greater rate than the aged tissue. Both young and aged tissues treated with Y-27632 relaxed completely, although the young tissue relaxed at a significantly greater rate than the aged tissue. Data indicated that as the tissue ages, the effectiveness of myosin phosphatase decreases. Furthermore, age-related changes in the Rho kinase pathway inhibited the rate of relaxation, without affecting total relaxation. Taken together, these results suggest that age-related changes in vascular smooth muscle may be linked to changes in specific enzyme pathways that regulate the activity of this muscle. Whether these changes are ultimately linked to the development of vascular diseases such as hypertension remains to be determined.