Effect of deuterium oxide (D2,O) on vascular smooth muscle

McWilliam, Tina Marie (1990) Effect of deuterium oxide (D2,O) on vascular smooth muscle. Masters thesis, Memorial University of Newfoundland.

[English] PDF (Migrated (PDF/A Conversion) from original format: (application/pdf)) - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (12MB) [English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. (Original Version)

Abstract

The influence of deuterium oxide (D₂O) on aortic vascular smooth muscle was investigated. The effect on receptor- and voltage-operated calcium channels was studied with the use of phenylephrine and potassium chloride respectively. D₂O depressed the phenylephrine induced contraction response in a dose dependent manner with 50% inhibition of maximum contraction observed with 60% D₂O. The effect of 60% D₂O on phenylephrine induced contraction was reversible and not dependent on an intact endothelium. Sixty percent D₂O also reduced potassium chloride induced contractions by 50% indicating an effect on voltage operated calcium channels. Studies with Bay K 8644, an L-type calcium channel activator, and calcium free buffer studies, confirm an effect on utilization of extracellular calcium sources. Inhibition of sucrose induced contraction and acetylcholine and isoprenaline induced relaxation with 60% D₂O suggest an effect on intracellular calcium mobilization or on the contractile elements themselves. D₂O also affected both the pD₂' for nifedipine and the pA₂ for prazosin. Collectively, these data indicate that D₂O acts at multiple sites. -- In vivo studies indicate that chronic oral administration of 25% D₂O for 12 days reduces the blood pressure of spontaneously hypertensive (SHR) and normotensive (WKY) rats. However, the lowering of blood pressure did not result in a corresponding change in vascular smooth muscle contractility induced with phenylephrine and potassium chloride. These results support previous evidence that a reduction in blood pressure after hypertension has developed does not reduce vascular reactivity changes. A further acute study revealed that desensitization results from chronic exposure to D₂O such that 60% D₂O produces a significant depression of contraction only in aortic rings obtained from SHR and WKY rats which had not been chronically treated with twenty-five percent D₂O. -- KEY WORDS: Aorta; Calcium channels; Contraction; Deuterium oxide; Hypertension; In vitro; In vivo; Relaxation; Reversibility; Vascular smooth muscle

Actions (login required)

View Item