Rapid onset vasodilatation is blunted in obese humans

Obesity is a major risk factor for a variety of cardiovascular diseases associated with low levels of physical activity and reduced cardiorespiratory fitness (Vanhecke et al. 2009). Whereas exercise is recommended as a common non-pharmacological treatment option for obese patients (Weinstock et al. 1998, Mcinnis 2000), any impairment in vasodilatory responses could potentially impair exercise tolerance. As such, exploration into the mechanisms of any altered functional vasodilatation in obesity is an important research area. Only a few studies have examined vasodilatory responses to exercise in obesity and results are conflicting. Throughout three min of static forearm exercise, Negrao et al. (2001) demonstrated greater vascular resistance but maintained blood flow in the non-exercising forearm of obese adults. In contrast, during dynamic steady-state forearm exercise, Limberg et al. (2010a,b) showed obese otherwise healthy subjects exhibited preserved blood flow and vascular conductance. These results conflict animal models of obesity demonstrating impaired vasodilatation in response to in situ contractions (Xiang et al. 2005). Previous studies in humans focused on vasodilatory responses at steady state; however, activities of daily living are predominately brief, frequent transitions between rest and movement (i.e. household chores, moving from seated to standing, climbing a flight of stairs). In the context of short bursts in activity, mechanical factors associated with contraction may play a predominate role in regulating flow at the onset of movement (Clifford et al. 2006). In healthy adults, mechanical effects evoke an immediate and significant increase in blood flow after the release of the first muscle contraction (Sheriff et al. 1993, Naik et al. 1999, Tschakovsky & Sheriff 2004, Kirby et al. 2007, Carlson et al. 2008). This rapid onset vasodilatation peaks within approx. 4–6 cardiac cycles and its magnitude is proportional to the intensity of contraction (Tschakovsky & Sheriff 2004, Kirby et al. 2007, Carlson et al. 2008). Growing experimental evidence clearly demonstrates rapid onset vasodilatation as obligatory for this hyperaemic response (Naik et al. 1999, Hamann et al. 2004, Tschakovsky et al. 2004, Kirby et al. 2007); classical metabolic dilators cannot account for the rapid response (Wunsch et al. 2000). Whereas mechanical influences are thought to play an important role in blood flow responses to brief muscle contractions in healthy humans, the impact of obesity on rapid onset vasodilatation remains unknown. Notably, resistance arteries from skeletal muscles of obese rats exhibit altered myogenic responses (Frisbee et al. 2002) – suggesting mechanical factors associated with contraction may negatively impact vasodilatation in human obesity. From a mechanistic perspective, rapid onset vasodilatation is dependent upon potassium channel opening (Armstrong et al. 2007), and obese animals exhibit impaired potassium channel-mediated vasodilatation (Hodnett et al. 2008). With this background in mind, we tested the hypothesis that obese, otherwise healthy adults, would exhibit reduced muscle rapid onset vasodilatation in response to a brief, single forearm contraction compared with healthy lean controls.