title: Abnormalities in the sodium transport as the causative factor for enhanced norepinephrine overflow in the spontaneously hypertensive rat.
abstract: These studies were designed to investigate whether alterations in the sodium transport could account for the enhanced transmitter release observed during sympathetic nerve stimulation in SHR. In the isolated in vitro perfused rat kidneys, norepinephrine (NE) storage sites were labelled with [3H]-NE and the transmitter overflow was evaluated at various frequencies during the periarterial nerve stimulation. Stimulus-induced transmitter overflow was consistently greater and the maximal overflow was 2-fold higher in the kidneys of SHR when compared to that of normotensive WKY. Addition of ouabain, a selective inhibitor of the sodium pump, (10(-3)M in the medium) significantly enhanced stimulus induced overflow in both the groups. However, the magnitude of these changes was significantly greater in WKY than in SHR kidneys suggesting that the membrane Na+-pump was functionally less efficient in the SHR. Ouabain virtually eliminated the differences between the two groups in that the transmitter overflow was essentially identical in SHR and WKY in the presence of the Na+-pump inhibitor. These observations suggest that a genetic abnormality in the neuronal sodium pump could account for the enhanced sympathetic transmitter overflow and contribute to hypertension in the spontaneously hypertensive rats.
authors.affiliation: Department of Pharmacology, University of Houston, Texas 77004.
authors.forename: M L
authors.initials: ML
authors.lastname: Steenberg
authors.forename: M F
authors.initials: MF
authors.lastname: Lokhandwala
authors.forename: B S
authors.initials: BS
authors.lastname: Jandhyala
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004558:Electric Stimulation; D007668:Kidney / Q000098:blood supply / Q000294:innervation; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015222:Sodium Channels / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D015222:Sodium Channels; D010042:Ouabain; D009638:Norepinephrine