Kevin P J O'Kane

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The physiological effects of angiotensin-converting enzyme (ACE) inhibition may be in part mediated by bradykinin. We investigated the effect of coadministration of the specific bradykinin B(2) receptor antagonist icatibant on hemodynamic and neurohormonal responses to acute intravenous ACE inhibition in normal men on a normal sodium diet. We performed a(More)
BACKGROUND Although local inhibition of the generation or actions of endothelin-1 has been shown to cause forearm vasodilatation, the systemic effects of endothelin receptor blockade in healthy humans are unknown. We therefore investigated the cardiovascular effects of a potent peptide endothelin ETA/B receptor antagonist, TAK-044, in healthy men. METHODS(More)
This study was performed to evaluate the antihypertensive efficacy and tolerability of candesartan cilexetil 8-16 mg once-daily in comparison with placebo in elderly hypertensive patients. Forty-one hospital and general practice centres in the Netherlands and in the United Kingdom enrolled 350 patients over 65 years of age with essential hypertension (WHO(More)
1. Studies in animals indicate that bradykinin relaxes blood vessels directly through an action on smooth muscle and indirectly through the release of endothelium-derived mediators. Its precise mechanism of action in the human arterial circulation is not yet known. 2. In this study the effects of a specific inhibitor of nitric oxide synthase,(More)
An insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene accounts for approximately 50% of the variance in plasma ACE concentration: deletion homozygotes (DD) have the highest, and insertion homozygotes (II) the lowest ACE concentrations. ACE is responsible for the generation of angiotensin II, which is implicated in the(More)
The renin-angiotensin system is intimately involved in the control of sodium and water balance, the activity of the sympathetic nervous system, mitogenesis and the regulation of vascular tone. There is evidence that many of these effects may be controlled at a local level by independent tissue renin-angiotensin systems. Drugs that are specific inhibitors of(More)
The genetic contribution to major disorders is increasingly recognized. This usually reflects interaction at a number of different loci to determine the eventual clinical phenotype, and dissecting out the role of individual components is a complex task. However, a clear understanding of the genetic factors involved in diseases such as hypertension,(More)
OBJECTIVES The goal of this study was to determine the long-term effects of estrogen replacement therapy on the response to endothelin-1 (ET-1) in postmenopausal women with coronary heart disease. BACKGROUND It is thought that the vasoconstrictor ET-1 is involved in the development and progression of atherosclerosis. Estrogen replacement may slow the(More)
BACKGROUND On-demand therapy may offer an effective approach to the long-term management of gastro-oesophageal reflux disease (GORD) without oesophagitis. AIM To examine the efficacy of the novel proton pump inhibitor esomeprazole as on-demand therapy in endoscopy-negative GORD. PATIENTS AND METHODS Endoscopy-negative GORD patients who achieved complete(More)
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