The work presented in this thesis involves new methods of using nuclear magnetic resonance spectroscopy (NMR) to study ion transport <i>in vivo</i> in hypertension. A new NMR technique was developed which allowed measurement of absolute concentrations of rubidium (potassium) <i>in vivo</i>. This method was used to study rubidium (potassium) kinetics in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats and showed evidence for increased potassium efflux and increased Na<SUP>+</SUP>/K<SUP>+</SUP>-ATPase activity in SHR skeletal muscle <i>in vivo</i>. NMR was also used to study <i>in vivo</i> Na<SUP>+</SUP>/H<SUP>+</SUP> antiporteractivity in the skeletal muscle of the rat and it was found that Na<SUP>+</SUP> /H^+ antiporter activity is increased by β2-adrenoceptor stimulation and by increasing the activity of the sympathetic nervous system. This stimulation of Na^+/H^+ antiporter activity in skeletal muscle by the sympathetic nervous system may be part of the well known but poorly understood 'fright and flight' mechanism. Using these new NMR techniques it was found that Na^+/H^+ antiporter activity is increased in SHR skeletal muscle <i>in vivo</i>. In addition, this difference in antiport activity can be removed by blocking L-type calcium channels. These differences in ion transport in SHRs occurred in association with increased skeletal muscle relaxation following contraction which is similar to the finding in vascular smooth muscle in essential hypertension. Despite differences in <i>in vivo</i> Na^+/H^+ antiporteractivity and <i>in vivo</i> potassium fluxes in SHRs no difference was found in either intracellular steady-state concentrations of potassium ions, hydrogen ions or bicarbonate. In addition, there was no difference in intrinsic cell buffering in SHRs <i>in vivo</i> compared with WKY rats. On the basis of these findings a new hypothesis is proposed which links ion transport abnormalities found in hypertension with cell volume and pH regulation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:662679 |
| Date | January 1992 |
| Creators | Syme, Paul David |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/20233 |
Page generated in 0.0018 seconds