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Title: Clinical studies on prostacyclin
Author: Webster, J.
ISNI:       0000 0001 3565 1282
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1981
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Plasma levels of 6-oxo-prostaglandin F1a (6-oxo-PGFla), thestable hydrolysis product of prostacyclin (PGI2) were measured by gas chromatography-mass spectrometry. In 62 normal subjects a mean ± SD plasma level of 115.5 ± 27.2 pg/ml was obtained. Plasma levels declined significantly with age. Soluble aspirin (1200 mg) a known inhibitor of cyclo-oxygenase, reduced plasma levels of 6-oxo-PGFla and forearm ischaemia, a known stimulus to PGI2 production, increased plasma levels of 6-oxo-PGF1 . Plasma levels of 6-oxo-PGF1awere significantly reduced in men witA proliferative diabetic retinopathy compared with age-matched normal controls while male diabetics with background or no retinopathy formed an intermediate group. Plasma levels of 6-oxo-PGF1a were barely detectable in three patients with thrombotic thrombocytopenic purpura and in one patient with severehaemolytic uraemic syndrome. A within-patient randomized double-blind crossover study was performed to evaluate the effects of bendrofluazide 10 mg daily or placebo in patients with mild essential hypertension. Significant reductions in lying, standing and post-exercise blood pressure were seen after both three day's and ten week's treatment. Plasma levels of 6-oxo-PGF1a were significantly increased by both three day's and ten week's therapy with bendrofluazide, possibly reflecting increased PGI2 biosynthesis. No correlation was observed between the increase in 6-oxo-PGFls and the reduction in blood pressure, urinary electrolyte excretion, plasma renin activity or in the pressor response to infused noradrenaline. In preliminary studies neither propranolol nor captopril showed significant effects on plasma levels of 6-oxo-PGF1Q but in normal volunteers a three day dietary sodium supplement of 200 mmol sodium daily produced a small but significant reduction in plasma levels of 6-oxo-PGF1a. In normal subjects, intravenous infusion of PG12 produced facial flushing, tachycardia and a small fall in diastolic blood pressure, together with inhibition of ADP-induced platelet aggregation. Neither posture nor exercise exaggerated the cardiovascular responses to PGI2, indicating a predominantly arteriolar dilating effect. Infusion of PGI2 into the brachial artery increased forearm blood flow while PGI2 also exhibited local venodilator effects when infused into the dorsal hand vein in normal subjects. In a small number of patients with severe hypertension, PGI2 infusion resulted in a profound hypotensive effect.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine