Watson, Michael Leonard

2018-01-31T11:39:48Z

2018-01-31T11:39:48Z

1985

Renal function is a key factor in the long term control of blood pressure. The kidney has a large capacity to synthesise. a.number of prostaglandins, particularly PGE₂ and PGI₂. These compounds are systemic vasodilators and when infused into kidney the cause renal vasodi.latation,renin release and'an'increase in sodium excretion. By virtue of these potential actions they may, therefore, have an important role in the control of renal function and ultimately in the long term control of blood pressure. In this: thesis the results of a.number of studies in both animals and man are described which aim to clarify the importance of prostaglandins as determinants of renal function. Both radioimmunoassay and gas chromatography - mass spectrometric methods for measuring prostaglandins and their metabolites were developed.

These methods were then employed to determine the effect of changes in sodium balance on renal PGE synthesis in conscious dogs during the development of one clip -two kidney hypertension. Sodium balance was manipulated during the early phase of this process by the controlled removal of salt and water using haemofiltration. interrelationship between prostaglandins and the renin- angiotensin system was explored in a series of experiments; firstly by measuring changes in systemic PGI2 synthesis in conscious dogs during infusion of angiotensin II and secondly by measuring changes in renal haemodynamics, sodium excretion and PGE excretion in response to infusion of different doses of angiotensin II before and after the development of one clip -two kidney hypertension. In view of the importance of renal interstitial cells as a source of prostaglandins, changes in'thei.r morphology was also studied in normotensive and hypertensive dogs.

The second part of the thesis concentrates on studies in man. The effect of rapid expansion of the extracellular fluid volume on renal PGE and systemic PGI₂ synthesis was examined. Systemic PGI₂ synthesis was measured during varying levels of activity of the renin-angiotensin system, induced by changes,in dietary sodium intake and also by comparing synthesis. before and after removal of an aldosterone secreting adenoma from patients.

The results support the hypothesis that renal PCE synthesis is important.in maintaining renal blood flow in the presence of vasoconstrictor stimuli. Such as angiotensin II. The role of changes it renal PGE synthesis during the development of renal ' hypertension is less clear but the results are consistent with the hypothesis that PGE may serve as an intrarenal natriuretic agent. Systemic PGI₂. synthesis does not appear to be of importance in modulating :the systemic vaso- constrictor effects of angiotensin II. The observation of relative increases in its synthesis during period of high sodium intake, immediately after a rapid intravenous infusion of sodium chloride and in the presence of hyperaldosteronism are all consistent with the concept that changes in vascular filling pressure may be modulated by changes in systemic PGI₂ synthesis.

http://hdl.handle.net/1842/27622

The University of Edinburgh

Annexe Thesis Digitisation Project 2017 Block 16

Prostaglandins, renal function and the development of hypertension

Thesis or Dissertation

MD Doctor of Medicine