Effects of age and caloric restriction in the vascular response of renal arteries to endothelin-1 in rats

Cardiovascular alterations are the most prevalent cause of impaired physiological function in aged individuals with kidney being one the most affected organs. Aging-induced alterations in renal circulation are associated with a decrease in endothelium-derived relaxing factors such as nitric oxide (NO) and with an increase in contracting factors such as endothelin-1(ET-1). As caloric restriction (CR) exerts beneficial effects preventing some of the aging-induced alterations in cardiovascular system, the aim of this study was to analyze the effects of age and caloric restriction in the vascular response of renal arteries to ET-1 in aged rats. Vascular function was studied in renal arteries from 3-month-old Wistar rats fed ad libitum (3 m) and in renal arteries from 8-and 24-month-old Wistar rats fed ad libitum (8 m and 24 m), or subjected to 20% caloric restriction during their three last months of life (8 m-CR and 24 m-CR). The contractile response to ET-1 was increased in renal arteries from 8 m and 24 m compared to 3 m rats. ET-1-induced contraction was mediated by ET-A receptors in all experimental groups and also by ET-B receptors in 24 m rats. Caloric restriction attenuated the increased contraction to ET-1 in renal arteries from 8 m but not from 24 m rats possibly through NO release proceeding from ET-B endothelial receptors. In 24 m rats, CR did not attenuate the aging-increased response of renal arteries to ET-1, but it prevented the aging-induced increase in iNOS mRNA levels and the aging-induced decrease in eNOS mRNA levels in arterial tissue. In conclusion, aging is associated with an increased response to ET-1 in renal arteries that is prevented by CR in 8 m but not in 24 m rats.