The results of this investigation provide evidence that heat and cold stress, physical exercise of the legs and hands, and caffeine ingestion induce physiological effects on various cardiovascular system response parameters in humans. When cold stress was applied to the forearm, mean pulse wave amplitude and heart rate decreased compared to the control. When the subject’s forearm is exposed to the ice-cold surface of the bag, sensory afferents at the area of exposure trigger a systemic sympathetic activation leading to marked vasoconstriction (Lafleche et al., 1998). This elevates pulse pressure by narrowing the blood vessels, increasing the resistance, and in turn, decreasing the rate at which the heart beats, due to catecholamine release, such as norepinephrine. This is in accordance with the finding that full-hand immersion into water at 5ºC (the cold pressor test) yields an increase in blood norepinephrine concentration (Besnard et al., 2000).
When norepinephrine is released by the autonomic nervous system into the bloodstream, it binds to α1-adrenoreceptors found on endothelial cells lining the blood vessels. This activates a G-protein coupled receptor which leads to smooth muscle contraction (Eschenhagen, 2008). In fact, several authors have observed that local cooling induces vasoconstriction in distant areas of the body (Gooden et al., 1976). Therefore, it is possible that the cold had exerted its effect around the body, rather than just locally. The data obtained in this experiment is consistent with the hypothesis that, acute decreases in heart rate and cardiac output are associated with the exposure to cold temperatures. One possible reason why mean pulse wave amplitude, heart rate, and R-pulse intervals did not shown significant differences before and after treatment, may be due to the methodology used for cooling the surface of the forearm. For instance, the forearm may have inadequately been covered by the ice-bag’s surface area, restricting the subject’s forearm from full exposure. A more effective means of approaching this experiment would be to fully submerge the subject’s hand into an ice water bath to accurately measure the stressors effect on the heart.
When heat stress was applied to the forearm, mean pulse wave amplitude and heart rate significantly increased compared to the control. It has been shown that heat stress induces a thermoregulatory process known as vasodilation, as opposed to vasoconstriction, to increase blood flow. Cutaneous vasodilation during heat stress promotes heat dissipation from body core to skin by increasing the diameter of blood vessels, and thus, decreasing resistance (Kamijo et al., 2008). As resistance decreases, the subject’s cardiac output – a parameter equal to the heart rate multiplied by the volume of blood ejected during ventricular systole – also increases, which, in turn, causes a rise in the mean arterial pressure (Kamijo et al., 2008). It is possible that vasodilation may explain the significant increases observed in pulse wave and heart rate.
Cutaneous vasodilation during heat stress is induced through two mechanisms: (1) Withdrawal of sympathetic vasoconstrictor activity, and (2) enhancement of an active sympathetic vasodilator system (Kamijo et al., 2008). It is assumed that the heat emitted from the bag of warm water may have stimulated the peripheral warm-sensitive neurons that mainly belong to unmyelinated C-fiber afferents found in the peripheral nerves of somatic sensory system (Kamijo et al., 2008). The input of this sensory information to the hypothalamic temperature-regulating centers would contribute to the initiation of active cutaneous vasodilation, either through the release nitric oxide, bradykinin, or adenosine by local paracrine agents from endothelial cells or by the secretion of catecholamines such as epinephrine (Ajisaka et al., 2003). Although further biochemical investigations are required to accurately monitor this process, the data obtained in this experiment is consistent with the proposed hypothesis in the view that acute increases in heart rate and cardiac output are associated with exposure to elevated temperatures.
The present data shows a close relationship between the effects of mild leg exercises and increases to heart rate and volume pulse. Like the effect exerted during heat stress, physical exercise also stimulates the body’s core temperature, which functions as a major factor driving active sympathetic vasodilator activity (Kamijo et al., 2008). Berry et al., (1997) demonstrated that a 30-minutes bout of moderate cycling using both legs decreased pulse wave amplitude; this phenomenon was also observed in the experiment conducted. Pulse wave amplitude is a common variable used to index the measurement of arterial wall stiffness (elasticity) (Ajisaka et al., 2003). The lower the artery stiffness, the higher its buffering capacity; a high buffering capacity suggests that the artery can efficiently absorb the energy during pulsatile blood flow and reduce the energy loss by making the blood flow smooth (Ajisaka et al., 2003). Consequently, during an exercise, it is favourable that arterial stiffness (pulse wave amplitude) decrease, in order to increase blood flow and meet the oxygen demands in active muscles (Ajisaka et al., 2003).
In a similar experiment formed performed by Ajisaka et al., (2003), it was suggested that the increase in heart rate and decrease in pulse wave amplitude (arterial stiffness) may be attributed to regional factors, such as increases in temperature, exercising muscle-derived metabolites (adenosine, potassium), and flow-mediated vasodilators (nitric oxide) – all of which might contribute to vasodilation of vascular smooth muscle. In particular, the production of nitric oxide, which is a potent endothelial vasodilator, has been shown to reduce the vasoconstrictor response to α-adrenoreceptor stimulation and increase blood flow associated with acute exercise (Collins et al., 1993). Therefore, it is possible that the exercise-induced differences observed between the post-exercise changes to heart rate and pulse volume are due to the release of nitric oxide. However, the data obtained cannot fully specify which factor is actually responsible; this is a limitation of the present experiment.
Since the general effect of physical exercise is increased blood flow throughout the body, it is possible that the cardiovascular effects observed during the hand exercise experiment occurred via a similar process mentioned above. The data obtained in both experiments is consistent with the hypothesis that, acute physical exercise of the hands and legs will stimulate cardiac response.
The results obtained after performing the caffeine investigation provide evidence that caffeine alters cardiovascular response in humans. A 100 milligrams dose of caffeine increased heart rate, while pulse wave amplitude and R-pulse interval decreased. A decrease in pulse wave amplitude suggests that aortic stiffness has decreased. However, in a study conducted by Hirata et al., (2003), it was discovered that pulse pressure increased significantly after caffeine had been administrated, denoting an increase in aortic stiffness. This inconsistency may be due to one of two reasons: (1) The study conducted by Hirata et al.(2003) was based on a higher dose of caffeine (250 mg), or (2) an inadequate number of subjects (n=2) took part in the present experiment; thus, significance could not be attributed. Therefore, although caffeine increases heart rate, the mechanism it uses to stimulate a cardiovascular response must differ than that exerted by physical exercise, as predicted in our hypothesis. The caffeine induced alterations in this study were probably due to antagonism of adenosine receptors. When caffeine binds to α1 and α2 adenosine receptors (Boekema et al., 1987), unbound adenosine attenuates the release of epinephrine from the adrenal medulla (Graham et al., 1993). Since epinephrine is a potent vasoconstrictor, the more caffeine available, the greater the heart rate since blood vessels are not vasoconstricted (Daniels et al., 1998).
Caffeine may have also exerted its effects on cyclic adenosine monophosphate (cAMP), a second messenger ubiquitously expressed and shown to be involved in many metabolic pathways, including those activated by epinephrine via β-adrenoreceptors (G-protein coupled receptor). When caffeine is present, the enzyme responsible for dephosphorylating cAMP – phosphodiesterase – is inhibited. This causes cAMP to persist in cells for a longer period of time, activating cAMP-dependent protein kinases, which subsequently phosphorylates enzymes that lead to cellular responses similar in nature to those observed in this study. Likewise, when cytosolic cAMP concentrations are high, calcium channels located on the plasma membrane open. An increase in cytoplasmic calcium causes smooth muscle contraction. Therefore, it is possible that the cAMP produced by adenylate cyclase, following the activation of β-adrenoreceptors, was active for a longer period of time due to caffeine’s inhibitory effect on cellular phosphatases.
In summary, the findings presented in this study suggest that external changes in temperature, physical exercise, and caffeine can influence the cardiovascular system through multiple mechanisms. Since many of the models used to describe the physiological processes that took place are based on biochemical reactions, further molecular and biochemical investigations are required to resolve these details. In addition, these results also suggest that ECG recordings and volume pulse are excellent tools for investigating symptoms and signs associated with various cardiovascular system complications.
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