Time-dependent increases in ouabain-sensitive Na +, K +-ATPase activity in aortas from diabetic rats: The role of prostanoids and protein kinase C

• Published in: Life sciences (1973) Vol. 87; no. 9; pp. 302 - 308
• Main Authors: Gallo, Luana C., Davel, Ana Paula C., Xavier, Fabiano E., Rossoni, Luciana V.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 28-08-2010
• Subjects: Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - enzymology; Aorta, Thoracic - physiopathology; Blotting, Western; COX-2; Cyclooxygenase 2 - biosynthesis; Diabetes; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - physiopathology; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Endothelium, Vascular - physiopathology; Male; Ouabain - pharmacology; Ouabain-sensitive Na +, K +-ATPase activity; Prostaglandin H2 - metabolism; Prostaglandins - metabolism; Prostanoids; Protein kinase C; Protein Kinase C - metabolism; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase - metabolism; Thromboxane A2 - metabolism; Time Factors; Vasoconstriction - drug effects; Vasodilation - drug effects; Protein kinase C; Ouabain-sensitive Na +, K +-ATPase activity; Diabetes; COX-2; Prostanoids
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2010.07.005

Na
+, K
+-ATPase activity contributes to the regulation of vascular contractility and it has been suggested that vascular Na
+, K
+-ATPase activity may be altered during the progression of diabetes; however the mechanisms involved in the altered Na
+, K
+-ATPase activity changes remain unclear. Thus, the aim of the present study was to evaluate ouabain-sensitive Na
+, K
+-ATPase activity and the mechanism(s) responsible for any alterations on this activity in aortas from 1- and 4-week streptozotocin-pretreated (50
mg
kg
−
1
, i.v.) rats.
Aortic rings were used to evaluate the relaxation induced by KCl (1–10
mM) in the presence and absence of ouabain (0.1
mmol/L) as an index of ouabain-sensitive Na
+, K
+-ATPase activity. Protein expression of COX-2 and p-PKC-βII in aortas were also investigated.
Ouabain-sensitive Na
+, K
+-ATPase activity was unaltered following 1-week of streptozotocin administration, but was increased in the 4-week diabetic aorta (27%). Endothelium removal or nitric oxide synthase inhibition with
l-NAME decreased ouabain-sensitive Na
+, K
+-ATPase activity only in control aortas. In denuded aortic rings, indomethacin, NS-398, ridogrel or Gö-6976 normalized ouabain-sensitive Na
+, K
+-ATPase activity in 4-week diabetic rats. In addition, COX-2 (51%) and p-PKC-βII (59%) protein expression were increased in 4-week diabetic aortas compared to controls.
In conclusion, diabetes led to a time-dependent increase in ouabain-sensitive Na
+, K
+-ATPase activity. The main mechanism involved in this activation is the release of TxA
2/PGH
2 by COX-2 in smooth muscle cells, linked to activation of the PKC pathway.