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dc.contributor.authorVeniero, Joseph Constantine
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 56-05, Section: B, page: 2511.;Advisors: Raj K. Gupta.
dc.description.abstractEssential hypertension (EH) is a highly prevalent and often unnoticed disease which is associated with increased risk of cardiovascular morbidity and mortality. Previous work has shown that intracellular cations are involved in the pathophysiology of EH. My research has attempted to define an abnormality of intracellular K{dollar}\sp+{dollar} in EH by using NMR spectroscopy to measure intracellular cations.;I have measured the steady-state intracellular free potassium concentration {dollar}\rm(\lbrack K\sp+\rbrack\sb{lcub}i{rcub}){dollar} in hypertensive rat aortae as a model for vascular smooth muscle tissue. I developed an NMR procedure for non-invasively measuring the {dollar}\rm\lbrack K\sp+\rbrack\sb{lcub}i{rcub}{dollar}, in aortae and demonstrated a significant deficit of {dollar}\rm\lbrack K\sp+\rbrack\sb{lcub}i{rcub}{dollar} in the aortae of the spontaneously hypertensive rat, compared to normotensive control aortae.;A similar derangement of {dollar}\rm\lbrack K\sp+\rbrack\sb{lcub}i{rcub}{dollar} in the erythrocytes of patients with EH was found which was normalized upon anti-hypertensive therapy. I also found that the {dollar}\rm\lbrack K\sp+\rbrack\sb{lcub}i{rcub}{dollar} was correlated inversely to {dollar}\rm\lbrack Ca\sp{lcub}2+{rcub}\rbrack\sb{lcub}i{rcub}{dollar} and directly to {dollar}\rm\lbrack Mg\sp{lcub}2+{rcub}\rbrack\sb{lcub}i{rcub}{dollar}. An NMR method of measuring the K{dollar}\sp+{dollar} efflux rate in these cells was developed and utilized for investigating the mechanism of decreased {dollar}\rm\lbrack K\sp+\rbrack\sb{lcub}i{rcub}{dollar} in hypertension. K{dollar}\sp+{dollar} efflux measurements in the presence of the transport inhibitors quinine and furosemide showed that the predominant pathway for potassium efflux in the hypertensive erythrocyte is the {dollar}\rm\lbrack K\sp+\rbrack\sb{lcub}i{rcub}{dollar} calcium-activated potassium channel. A greater open probability of this channel, due to higher {dollar}\rm\lbrack Ca\sp{lcub}2+{rcub}\rbrack\sb{lcub}i{rcub}{dollar} in the hypertensive erythrocyte, would cause loss the observed loss of {dollar}\rm\lbrack K\sp+\rbrack\sb{lcub}i{rcub}{dollar}.;Finally, investigations of the intracellular ionic effects of acute exposure to Pb{dollar}\sp{lcub}2+{rcub}{dollar}, which may induce hypertension, were undertaken. I showed that lead exposure caused dose-dependent changes in the intracellular ionic environment of human erythrocytes, such that, {dollar}\rm\lbrack Na\sp+\rbrack\sb{lcub}i{rcub}{dollar} and {dollar}\rm\lbrack Ca\sp{lcub}2+{rcub}\rbrack\sb{lcub}i{rcub}{dollar} were increased, and {dollar}\rm\lbrack K\sp+\rbrack\sb{lcub}i{rcub}{dollar} was decreased. These changes are similar to those observed in the hypertensive cell.;In summary, my work defines a common abnormality in the intracellular ionic environment, particularly in the intracellular K{dollar}\sp+{dollar}, in human EH, Pb{dollar}\sp{lcub}2+{rcub}{dollar}-induced hypertension and the genetic spontaneous hypertension in the rat, and provides a more complete ionic description of a hypertensive cell. The deficit of intracellular potassium in vascular tissue which I described provides a basis for understanding the beneficial effects of potassium supplementation in hypertension.
dc.publisherProQuest Dissertations & Theses
dc.subjectAnimal Physiology.
dc.titleNuclear magnetic resonance studies of intracellular potassium in essential hypertension

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