Influence of age on nitric oxide modulatory action on Na(+), K(+)-ATPase activity through cyclic GMP pathway in proximal rat trachea.

Age-related changes in the modulatory action of nitric oxide (NO) on cyclic GMP levels and Na(+),K(+)-ATPase activity in the proximal rat trachea were investigated using sodium nitroprusside, 8-bromo-cyclic GMP and okadaic acid. At 24 months, both control activities of Na(+), K(+)-ATPase and Mg(2+)-ATPase were decreased when compared to the segments from 4- and 12-month-old animals. However, cyclic GMP levels were similar among the three ages. Sodium nitroprusside (100 microM) induced stimulation of Na(+),K(+)-ATPase activity in segments from both 4- and 12-month-old animals, but not 24-month-old animals. The effect was specific for Na(+),K(+)-ATPase since Mg(2+)-ATPase activity was unaffected. Sodium nitroprusside induced an increase in nitrates/nitrites and cyclic GMP levels in proximal segments at 4, 12 and 24 months. The 8-bromo-cyclic GMP (100 microM) induced a similar specific stimulation of Na(+),K(+)-ATPase activity in segments from 4- and 12- but not 24-month-old animals. Okadaic acid (1 microM), a phosphatase-1 inhibitor, increased proximal Na(+), K(+)-ATPase but not Mg(2+)-ATPase activity in tissues from 4-, 12- and 24-month-old animals. Our results suggest that aging affects cyclic GMP pathway in proximal rat trachea by an action at the level of the cyclic GMP-dependent protein kinase.