Authors' reply: Nonselective nonsteroidal anti-inflammatory drugs and increased cardiovascular events: emotional stress could be the explanation

We noted with interest the comments of Dr Sutton [1] that ‘a Google search on aldosterone, stress, mood produced ‘52 000 English or French pages’ in 0.33 s' and that our paper [2] ‘made no mention of stress as a possible cause of increases in aldosterone during NSAID treatment’. Our research [2] was conducted in vitro using human kidney (and liver) microsomes and demonstrated that nonselective NSAIDs inhibit the glucuronidation of aldosterone, predicating an increase in plasma and tissue (renal) aldosterone concentration in vivo. To suggest that stress is an explantion for our in vitro data indicates that Dr Sutton either did not read or understand the article and its conclusions. Although aldosterone synthesis and secretion is regulated principally by angiotensin II, extracellular potassium and ACTH we concur with Dr Sutton that other factors can stimulate or inhibit aldosterone production in vivo including catecholamines, 5-hydroxytryptamine, heparin and vasoactive intestinal polypeptide [3]. Undoubtedly aldosterone is a key cardiovascular hormone contributing to the pathophysiology of heart failure [3] and the development of hypertension [4]. The potential for a synergistic effect of NSAIDs and ‘stress’ on aldosterone concentration in vivo might lead us to conclude that in stressful situations the adage ‘take an aspirin and lie down’ should be revised simply to ‘lie down’!