The pressor effects of angiotensin II

Brown, Alison Jane (1981) The pressor effects of angiotensin II. PhD thesis, University of Glasgow.

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A method has been developed in which intravenous infusions can be given and arterial pressure and metabolic balance measured for up to 21 days in conscious unrestrained rats. Using the method, a comparison was made of the direct vasoconstrictor and slow pressor effects of angiotensin II (AII). Both were related to concurrent plasma AII concentrations. Nine female Wistar rats were infused intravenously firstly with 5% dextrose for 3 days, then AII at 20ng/kg/min at 2.4mls/day for 7 days and finally with dextrose for 3 days. Nine control rats received dextrose throughout. AII raised mean arterial pressure (MAP) progressively reaching a peak on the 7th day, 49.7 mmHg higher than control (p< 0.001). MAP in control rats did not change significantly. The direct pressor response to AII (30,90 and 270ng/kg/min, each for 1 hour) did not change during prolonged AII infusion, although it was enhanced 4 hours after stopping prolonged infusion at a time when MAP was normal. Plasma angiotensin II levels during the progressive rise were 6 times those of control rats. In contrast, the pressor response to an hourly infusion of AII at 270ng/kg/min raising plasma levels to 32 times those of control, was on average 45.3+/-3 mmHg. This was close to the maximum direct effect since infusion at 810ng/kg/min raised MAP by an additional 9.3 mmHg only. Estimates of plasma AII were confirmed by chromatography. Infusion of AII reduced rather than increased the proportion of angiotensin III. Because changes of plasma angiotensin II concentration during prolonged infusion were closer to the physiological range of AII, this suggests that the slow pressor effect of AII may be more important than the direct effect in longterm regulation of MAP. Saralasin, an effective antagonist of AII, has a rapidly-acting agonist pressor effect. Prolonged infusion of saralasin has been used to assess the role of AII as a pressor hormone, but it is not known if saralasin has an additional slow developing pressor action like angiotensin II. This was tested in 8 female Wistar rats. Dextrose was infused intravenously for 2 days, followed by saralasin at 10ug/kg/min for 4 days and then dextrose for 2 days. MAP was recorded continuously. Saralasin gradually raised MAP in AII rats. After 4 days, MAP was 22 mmHg higher than in the control period. The diurnal variation of arterial pressure also increased during saralasin - MAP increased during the night between 9 p.m. and 9 a.m. and decreased during the day between 9 a.m. and 9 p.m. Variability of pressure also increased. A second group of rats was infused with AII at 20ng/kg/min for 4 days with continuous recording of arterial pressure. AII, as well as raising MAP slowly, also increased variability and diurnal rhythm of pressure. Saralasin and AII had no effect on food and water intake or on sodium balance. These findings, together with the structural similarities between AII and saralasin, suggest that both peptides are acting by a similar mechanism to raise arterial pressure. These properties of saralasin may also compromise interpretation of experiments in which the inhibitor is given by prolonged infusion to test the role of AII in the maintenance of MAP.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Tony Lever
Keywords: Pharmacology
Date of Award: 1981
Depositing User: Enlighten Team
Unique ID: glathesis:1981-72482
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06

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