Attenuation of Aging-Induced Vascular Dysfunction by Inhibition of Ca2+/Calmodulin Protein Kinase II (CaMKII) in Isolated Renal and Carotid Rat Arteries

Abstract

An increased prevalence of cardiovascular problems is recorded due to aging. The importance of aging as a potential risk factor for cardiovascular diseases has been increasing in most of the developing countries since populations continue to become older. Age-associated unusual structural changes that develop in blood vessels have been reported such as stiffening of the vasculature and fibrosis. CaMKII is a protein kinase that is present all-over in the body. In this study, it is suggested that acute inhibition of CaMKII-mediated signaling may be an effective method to prevent agingassociated detrimental changes in isolated blood vessels in SD male rats. The inhibitory effect of CaMKII in aging-induced renal/carotid vascular dysfunction was studied using the selective inhibitor KN-93. Isolated ring segments of the renal or carotid arteries were suspended in organ-bath chambers for measurement of isometric tension. Responses to Phenylephrine (PE), Endothelin-1 (ET-1), carbachol and Sodium Nitroprusside (SNP) were determined by measurement of changes in isometric tension. Results from this study showed abnormal vascular responses to vasoactive agonists in the vessels obtained from aged rats. Vasoconstrictor responses to phenylephrine were potentiated, while vasodilator responses to carbachol were reduced in blood vessels obtained from aged rats, in comparison to responses in young rats. Acute incubation of the blood vessels with KN-93 (10-5 M), an inhibitor of CaMKII, resulted in significant improvement in vascular function to both vasoactive agonists. Our results indicated that activation of CaMKII pathway contributes to aging-induced vascular dysfunction. Therefore, development of novel therapies that inhibit CaMKII pathway may prevent or reduce development of vascular abnormalities induced by aging.