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.
Scavone
C
C
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, Av. Lineu Prestes 1524, 05508-900, São Paulo, Brazil. cscavone@icb.usp.br
Glezer
I
I
Demarchi Munhoz
C
C
de Sena Bernardes
C
C
Pekelmann Markus
R
R
D000375:Aging / Q000502:physiology*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007202:Indicators and Reagents; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D054645:Protein Phosphatase 1; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D009599:Nitroprusside; D019319:Okadaic Acid; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP