Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394760
Title: The influence of the endothelium on the response of vascular smooth muscle
Author: Templeton, Alison Gibson Boyd
ISNI:       0000 0001 3516 0539
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1988
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Abstract:
This project was carried out to examine the influence of the vascular endothelium on the responses of the underlying smooth muscle. I have examined the influence of the endothelium on sensitivity of the smooth muscle to calcium and the interaction of a Ca2+-channel activator and blocker. A further study was carried out to examine how the initial tone affects the responses to both contractile and relaxatory agents and how the size of the induced tone affects the ability of Ach to cause relaxation. I studied the changes, if any, in this relationship in certain cardiovascular diseases. These effects were studied in an isolated aortic ring from the rat and also a complete vascular bed, the perfused rat tail. The following is a summary of the results: 1) Removal of the vascular endothelium from isolated aortic rings affects the sensitivity of the tissue to various agonists. The influence on the responses is greater for some agonists than for others. The agonists influenced to the greatest extent had both the pD2 and the maximum response significantly changed by removal of the endothelium: these agonists were either alpha1-adrenoceptor partial agonists or alpha2-adrenoceptor agonists in other tissues. The agonist affected to the least extent, the thromboxane mimetic drug U46619 showed no significant change on removal of the endothelium in either the maximum response or the pD2 value. 2) The presence of the vascular endothelium had no influence on the actions at alpha1-adrenoceptors, of the selective antagonists prazosin and corynanthine, or the alpha2-adrenoceptor antagonist, Wyeth 26703. The results using Wyeth 26703 did not support the possibility of alpha2-adrenoceptor stimulation releasing EDRF, since it had the same effect on responses to NA in tissues with both an intact and disrupted endothelium. 3) Increasing the initial length in aortic ring segments caused a length-dependent increase in the resting tension. The absence of the endothelium had no significant effect on the resting tensions compared with intact tissues. The size of the contraction to Phe (1uM) and relaxation to Ach (1uM) (tone induced by Phe) were dependent on the initial length of the preparation. The optimum stretch to demonstrate the proportionate effect of Ach (1uM) did not coincide with the optimum for Phe-induced contractions. 4) The size of the induced tone against which Ach produced relaxation affected the sensitivity to this agent. The greater the size of the induced tone the less sensitive the tissue was to relaxation. Atropine did not affect the size of the tone induced by NA but inhibited the relaxation to Ach. BAY-K 8644, a calcium channel facilitator, increased the tone induced by NA and inhibited the relaxation to Ach to a greater extent than would be expected by increase in tone alone. The cx2-antagonist drug Wyeth 26703, at concentrations where it acts selectively at alpha2-adrenoceptors (in other tissues), had no effect on NA-induced tone or on Ach-induced relaxation. 5) Using a maximal concentration of NA (3uM) in rat aortic rings, with either an intact or disrupted endothelium, in both a buffered and unbuffered calcium system, the contractile response was shown to be dependent on the concentration of extracellular calcium. At concentrations of calcium greater than 1.25mM the response started to fall off. This response was not potentiated using either system in the presence of BAY-K 8644 (1uM) but was significantly inhibited in the presence of nifedipine (1muM). 6) Using a submaximal concentration of NA (30nM) in the rat aortic rings either intact or disrupted, in an unbuffered system, again the response was shown to be dependent on the concentration of extracellular calcium. In this system the responses to NA (30nM) were potentiated by BAY-K 8644 (1-100nM). The potentiation was similar regardless of the presence of the endothelium and reached a maximum at BAY-K (10nM). In the presence of this drug the drop in maximum response at high concentrations of calcium was still evident. 7) In the presence of nifedipine (0.1-1muM) the responses to NA (30nM) were inhibited to a similar extent in both intact and disrupted rings. With this drug the drop in the maximum response at high calcium concentrations was not seen.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.394760  DOI: Not available
Keywords: Physiology
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