The shear stress of keeping cool: why being in the ‘hot seat’ might actually be good for your blood vessels

Abstract

An automobile comes off the assembly line stuck with its particular structural and functional traits which may remain inadequate or even dysfunctional in responding to driving challenges, unless public outcry and media coverage demands a recall. Thankfully, biological organisms are capable of constantly modifying themselves to better deal with both external and internal stresses that challenge their structural and functional capacity to maintain homeostasis. How are these stresses coupled to biological structural and functional adaptation? This remains a quintessential question in integrative physiology. Reductionist approaches have done much to identify specifics of signalling pathways that translate a given challenge into adaptations in the functional and structural building blocks of organism response capacity. However, the resurgence of innovative, integrative human in vivo studies in recent years demonstrates the critical contribution this type of research can play in advancing new perspectives on the underpinnings of physiological adaptation. The recent Journal of Physiology study by Green et al. (2010) is a case in point. These investigators set out to test the hypothesis that it is shear stress which couples repeated bouts of local heating (challenge to temperature homeostasis) to improvements in microvascular structure and function (biological response adaptation). The notion that mechanical stresses of blood flow can be a stimulus for vascular adaptation is nothing new and a wealth of findings from reductionist studies demonstrate this (for review see Hudlicka & Brown, 2009). However, no human study designs have been able to demonstrate such a cause–effect in the microvasculature in vivo. Green et al. (2010) measured the forearm skin blood flow response to incremental local heating, which is largely nitric oxide dependent, both before and after 4 and 8 weeks of 30-min-3-times-per-week repeated bilateral forearm heating challenges via water immersion (heat ‘training’). The frequency and duration could be compared to a moderate exercise training intensity for aerobic fitness improvement in sedentary persons. A cuff around the elbow in one arm was inflated during heat training to minimize the increase in skin perfusion during the heating bouts, isolating the impact of skin microvascular hyperaemia and attendant shear stress elevation on microvascular adaptation. Heat training increased the skin blood flow response to incremental heating, but only in the arm which was allowed to experience normal elevations in microvascular perfusion. Some additional key observations should be noted. First, during the heat training challenges skin vasodilatation in the cuffed arm was not different from that in the non-cuffed arm. So, local heating was evoking the normal vasodilatory response even when perfusion was restricted. Yet, the coupling of local temperature change to improvements in microvascular dilatation response did not occur unless mechanical forces of blood flow increased. Second, while the cuff substantially attenuated the increase in skin blood flow with local heating, the increase was still ∼40% of that in the uncuffed arm (∼4-fold vs.∼7-fold), suggesting a threshold shear stress for adaptation. However, it should be acknowledged that shear increase would not be proportional to flow increase because non-shear-mediated dilatation of resistance vessels would attenuate the actual shear experienced. Therefore, it remains to be confirmed what the actual threshold shear for adaptation would be. So why does this study warrant our close attention? First, it has identified increased shear as a stimulus for improving microvascular function in humans, and thereby focuses attention on finding ways to target increased blood flow to vascular regions as part of vascular disease prevention and treatment. But this is not all! This experimental model will allow examination of microvascular adaptations via skin biopsy and microdialysis. An innovative review by Martinez-Lemus and Meininger (Martinez-Lemus et al. 2009) summarizes evidence for repositioning and alignment of vascular smooth muscle cells and cytoskeleton protein rearrangement that rapidly (within a few days) redesigns the mechanical and structural characteristics of the vessel wall to optimize vasoregulatory responsiveness to a new ‘normal’. The approach developed by Green et al. (2010) will allow us to answer the question ‘What is the impact of the type of heat training bouts on structural and functional adaptation and their respective timelines?’ and significantly advance the use of shear stress as a therapeutic approach for vascular health. Second, the lack of vascular adaptation to local heating alone is particularly intriguing. Local heating represents an externally imposed challenge to regulation of temperature. Increases in microvascular perfusion represent a biological response aimed at limiting hyperthermia. Yet, it is coincident shear stress and not heating per se that appears essential for improving microvascular responsiveness to an external heating challenge. So, what aspect(s) of a given challenge to homeostasis actually represent the stimulus for adaptation? This is a question that is sorely lacking answers across a wide range of physiological systems. Perhaps, when investigating this question, the answers will not be found in obvious places.