Biomedical subjects

Colin A J Farquharson

Publications and source records attributed to Colin A J Farquharson.

4 recordsLinked to original sources

PubMed2006

Effect of spironolactone on C-reactive protein levels in patients with heart disease.

Animal evidence shows that aldosterone is pro-inflammatory and that aldosterone blockade is anti-inflammatory. Therefore part of the beneficial effect of aldosterone blockade that might contribute to it reducing mortality could be an anti-inflammatory effect. However, there are no previous data on whether aldosterone blockade is anti-inflammatory in man. We performed 4 separate studies to investigate whether spironolactone treatment would reduce levels of C-reactive protein (CRP), a marker of inflammation, in serum samples taken from patients suffering from different degrees of heart failure. We found in all 4 studies that spironolactone had no significant effect compared with placebo, on CRP levels in these patients. These studies provide evidence against the hypothesis that the clinical benefits produced by aldosterone blockade are due to it having anti-inflammatory effects.

Biomarkers↗

PubMed2002

Allopurinol improves endothelial dysfunction in chronic heart failure.

BACKGROUND: Increased oxidative stress in chronic heart failure is thought to contribute to endothelial dysfunction. Xanthine oxidase produces oxidative stress and therefore we examined whether allopurinol improved endothelial dysfunction in chronic heart failure. METHODS AND RESULTS: We performed a randomized, placebo-controlled, double-blind crossover study on 11 patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (1 month) versus placebo. Endothelial function was assessed by standard forearm venous occlusion plethysmography with acetylcholine, nitroprusside, and verapamil. Plasma malondialdehyde levels were also compared to assess significant changes in oxidative stress. Allopurinol significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean+/-SEM]: 181+/-19% versus 120+/-22% allopurinol versus placebo; P=0.003). There were no significant differences in the forearm blood flow changes between the placebo and allopurinol treatment arms with regard to sodium nitroprusside or verapamil. Plasma malondialdehyde was significantly reduced with allopurinol treatment (346+/-128 nmol/L versus 461+/-101 nmol/L, allopurinol versus placebo; P=0.03), consistent with reduced oxidative stress with allopurinol therapy. CONCLUSIONS: We have shown that allopurinol improves endothelial dysfunction in chronic heart failure. This raises the distinct possibility that allopurinol might reduce cardiovascular events and even improve exercise capacity in chronic heart failure.

Aged↗

PubMed2002

Gradual reactivation over time of vascular tissue angiotensin I to angiotensin II conversion during chronic lisinopril therapy in chronic heart failure.

OBJECTIVES: This study was designed to fully characterize vascular tissue angiotensin I (AI)/angiotensin II (AII) conversion changes over time in vivo in humans during chronic angiotensin-converting enzyme (ACE) inhibitor therapy. BACKGROUND: Plasma AII does not remain fully suppressed during chronic ACE inhibitor therapy. However, the plasma renin angiotensin system (RAS) might be dissociated from the vascular tissue RAS. We therefore set out to characterize the time course of vascular RAS reactivation during chronic ACE inhibitor therapy. METHODS: Vascular AI/AII conversion was studied in patients with chronic heart failure (CHF) taking chronic lisinopril therapy by the differential infusion of AI and AII into the brachial artery. A cross-sectional study was done to see whether there were differences in vascular AI/AII conversion according to New York Heart Association (NYHA) class. A second longitudinal study followed 28 patients with NYHA I to II CHF serially over 18 months to see whether vascular ACE inhibition was progressively lost with time despite ACE inhibitor therapy. A third study examined whether increasing the dose of lisinopril affected subsequent vascular ACE inhibition. RESULTS: In the cross-sectional study, vascular AI-to-AII conversion was significantly reduced in NYHA class III compared with class I/II (p < 0.05). In the longitudinal study, vascular ACE inhibition was significantly reduced at 18 months as compared with baseline (p < 0.001), suggesting gradual reactivation of vascular ACE in CHF over time. In the third study, tissue ACE inhibition could be restored by increasing the ACE inhibitor dose. CONCLUSIONS: Vascular AI/AII conversion reactivates over time during chronic ACE inhibitor therapy even if the CHF disease process is clinically stable. It also occurs as the CHF disease process progresses. Even if vascular AI/AII conversion has reactivated, it can be suppressed by increasing the dose of the ACE inhibitor.

Aged↗

PubMed2002

Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy.

Experimental studies have suggested a role for aldosterone and glucocorticoids in the pathogenesis of endothelial dysfunction. We therefore set out to characterize the acute effects of these hormones on vascular function in vivo in normal humans. A randomized, placebo-controlled, double-blind crossover study was performed on 16 healthy male volunteers (aged 19-29 years), examining the vascular effects of acute intravenous aldosterone infusion (12 pmol.min(-1).kg(-1) for 4 h) and of oral prednisolone (single 50 mg dose). Peripheral arterial vascular function was assessed by bilateral forearm venous occlusion plethysmography using two parallel study protocols. In the first protocol, eight subjects received, successively, acetylcholine, sodium nitroprusside, noradrenaline, angiotensin I and angiotensin II. The remaining eight subjects received, successively, acetylcholine, sodium nitroprusside, verapamil and noradrenaline. Aldosterone attenuated endothelium-dependent vasodilatation to acetylcholine as compared with either prednisolone or placebo (maximum vasodilatation: placebo, 357+/-38%; aldosterone, 257+/-21%; P <0.05). However, background endothelium-independent vasodilatation was not affected by either aldosterone or prednisolone. There were also no significant changes in vasoconstriction induced by angiotensin or noradrenaline following aldosterone or prednisolone treatment compared with placebo. Blood pressure and baseline blood flow did not differ between any of the study phases. Thus acute short-term systemic administration of aldosterone results in endothelial vasodilator dysfunction in normal men, providing evidence for an aldosterone-induced vasculopathy, which may be particularly relevant not only in heart failure but also in hypertensive patients with high aldosterone/renin ratios.

Adult↗