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.