Inverse regulation of endothelin-1 and nitric oxide metabolites in tissue with aging: implications for the age-dependent increase of cardiorenal disease

M Barton, T Lattmann, LV d'Uscio… - Journal of …, 2000 - journals.lww.com
M Barton, T Lattmann, LV d'Uscio, TF Lüscher, S Shaw
Journal of Cardiovascular Pharmacology, 2000journals.lww.com
Aging is an independent risk factor for cardiovascular and renal disease. The study reported
here investigated whether aging affects endothelin-1 (ET-1) and tissue levels of the nitric
oxide metabolites nitrite/nitrate in the kidney of rodents. Blood pressure was measured by
the tail-cuff method, ET-1 protein was determined by radioimmunoassay/high-performance
liquid chromatography (RIA/HPLC) and nitrite/nitrate was measured by ionpairing
chromatography. Compared to young male Wistar Kyoto rats (3 months of age), renal ET-1 …
Abstract
Aging is an independent risk factor for cardiovascular and renal disease. The study reported here investigated whether aging affects endothelin-1 (ET-1) and tissue levels of the nitric oxide metabolites nitrite/nitrate in the kidney of rodents. Blood pressure was measured by the tail-cuff method, ET-1 protein was determined by radioimmunoassay/high-performance liquid chromatography (RIA/HPLC) and nitrite/nitrate was measured by ionpairing chromatography. Compared to young male Wistar Kyoto rats (3 months of age), renal ET-1 protein levels in whole kidneys increased 3.6-fold at 24 months of age (from 70+/-9 to 253+/-43 pg/g tissue, p< 0.05, n= 6 each group). Similarly, renal ET-1 protein increased 1.7-fold in 18-month-old C57BL/6J mice as compared to 8-month-old adult animals (from 188+/-18 to 319+/-14 pg/g tissue, p< 0.05, n= 5-7). In female RoRo-Wistar rats (6, 18 and 33 months of age), tissue nitrite/nitrate levels in whole kidneys decreased with increasing age (from 232+/-25 to 130+/-6 [mu] mol/l/g tissue, p< 0.05). Thus, aging in healthy rodents is associated with a marked upregulation of renal ET-1 protein content and a decrease in tissue nitrite/nitrate levels in whole kidneys, independent of blood pressure. Activation of the ET pathway with aging may promote the development of age-dependent diseases such as glomerulosclerosis, hypertension and atherosclerosis.
Lippincott Williams & Wilkins