Biochemical and anatomical subcellular studies will be carried out to provide a unique insight into a link between membrane transport of norepinephrine (NE) and sodium extrusion in genetically hypertensive rats. Our studies on initial 3H-NE uptake by synaptosomes of brain stem and hypothalamus indicate that uptake in spontaneously hypertensive rat (SHR) is considerably lower than that of the age-matched Wistar-Kyoto (WKY). Na+-K+-ATPase activities in SHR synaptosomal samples is also lower than those of WKY. We wish to determine if any direct correlation exists between reduced uptake of NE and defective Na+-K+-ATPase system in membranes of axon terminals of hypertensive animals and whether these changes occur prior to the onset of hypertension due to sodium loading. We anticipate that the use of isolated synaptosomes and synaptic vesicle models will permit us to determine the underlying cellular mechanisms of NE uptake and Na+ extrusion and reveal any membrane alterations associated with hypertension. The major objectives of this project are: 1. To confirm our preliminary findings of initially reduced uptake of 3H-NE and suppressed Na+-K+-ATPase activity in the syntaptosomal fraction of SHR, and if they occur in young prehypertensive SHR. 2. To determine if reduced 3H-NE uptake and diminished Na+-K+-ATPase activity also occurs in the synaptosomal fraction of the hypertensive Dahl salt-sensitive rat strain. 3. To determine if the lesser degree of stimulation of 3H-NE uptake by high salt feeding in the Dahl salt-sensitive strain, noted in preliminary work, was due to a lesser degree of Na+-K+-ATPase induction. 4. To determine whether reduced Na+-K+-ATPase activity and the corresponding reduction of NE uptake observed in hypothalamus occur in other central and peripheral tissues; i.e., cerebral cortex, brain stem, cardiac tissue, red blood cells, mesenteric arteries and kidney of hypertensive rats. 5. To determine whether enhanced NE uptake by the hypothalamic storage vesicles of SHR (which we have reported) is associated with increased CA2+-MG2+-ATPase activities.
| Hano, T; Jeng, Y; Rho, J (1989) Norepinephrine overflow and re-uptake in perfused mesenteric arteries of Dahl salt-sensitive and salt-resistant rats. J Hypertens 7:43-9 |
| Hano, T; Jeng, Y; Rho, J (1989) Norepinephrine release and reuptake by hypothalamic synaptosomes of spontaneously hypertensive rats. Hypertension 13:250-5 |
| Hano, T; Rho, J (1989) Norepinephrine overflow in perfused mesenteric arteries of spontaneously hypertensive rats. Hypertension 14:44-53 |
