Caspers M L, Bussone M, Dow M J, Ulanski L J, Grammas P
Department of Chemistry, University of Detroit Mercy, MI 48219-0900.
Brain Res. 1993 Feb 5;602(2):215-20. doi: 10.1016/0006-8993(93)90685-g.
Acute hypertension, induced in rats by intravenous injection of angiotensin II, previously has been shown to increase cerebrovascular permeability to macromolecules. The purpose of this study was to examine the effect of acute hypertension on Na+,K(+)-ATPase, the enzyme responsible for controlling ionic permeability of the cerebromicrovascular endothelium. The K(+)-dependent p-nitrophenylphosphatase activity of the cerebromicrovascular Na+,K(+)-ATPase was determined using microvessels prepared from hypertensive and normotensive rats. When compared to controls, a 70% decrease (P < 0.02) in the maximum rate (Vmax) of the Na+,K(+)-ATPase from hypertensive rats was evident with no change in the Michaelis constant (KM). In contrast, gamma-glutamyltranspeptidase, a marker enzyme for cerebral endothelial cells, was not significantly affected. Sodium arachidonate (1-100 microM) inhibited the phosphatase activity of the Na+,K(+)-ATPase in microvessels isolated from both normotensive and hypertensive rats in a dose-dependent manner. Furthermore, poly-unsaturated fatty acids (sodium linoleate and arachidonate) evoked the greatest inhibition of the enzyme, while sodium oleate and sodium palmitate inhibited the Na+,K(+)-ATPase to lesser extents. This regulation of enzyme activity by fatty acids was comparable in control and hypertensive groups. In summary, the data indicate that the cerebromicrovascular Na+,K(+)-ATPase was altered as a consequence of acute hypertension and that poly-unsaturated fatty acids can modulate this enzyme in microvessels derived from hypertensive or control rats.
