Effects of invariant sympathetic activity on cutaneous circulatory responses to heat stress

This study investigated the role of sympathetic withdrawal on blood flow responses in cutaneous arteriovenous anastomoses (AVAs) and capillaries to direct and indirect heat stress. This was achieved by clamping sympathetic activity (SC) to the tail of anesthetized rats so that constrictor tone remained invariant during exposure of either the animal's tail (direct heating) or body (indirect heating) to a 35 degrees C environment. Flow through the AVAs in the tail was evaluated by laser-Doppler flowmetry (LDF), while capillary flow was investigated by videodensitometry measurements of blood cell velocity (CBV) in single capillaries within the subepidermal vascular plexus. Both direct and indirect heating significantly increased LDF and CBV. In comparison to blood flow responses in sham-operated control rats, the SC procedure resulted in significantly lower LDF responses to both direct and indirect heat stress. By contrast, the response of CBV was not significantly affected by SC during either mode of heating. These results indicate that the withdrawal of sympathetic constrictor tone plays a role in the response of cutaneous AVAs, but not precapillary arterioles, to direct as well as indirect heat stress. Additional studies on unanesthetized animals showed that superimposing body heating on a base of local heating elicited a further increase in LDF, suggesting that local heating does not deplete neural mediated dilatory reserve.     

Temperature regulation of the testes of the bottlenose dolphin (Tursiops truncatus): evidence from colonic temperatures

Dolphins possess a countercurrent heat exchanger that functions to cool their intra-abdominal testes. spermatic arteries in the posterior abdomen are juxtaposed to veins returning cooled blood from the surfaces of the dorsal fin and flukes. A rectal probe housing a linear array of five copper-constantan thermocouples was designed to measure colonic temperatures simultaneously at positions anterior to, within, and posterior to the region of the colon flanked by the countercurrent heat exchanger. Colonic temperatures adjacent to the countercurrent heat exchanger were maximally 1.3°C cooler than temperatures measured outside this region. Temporary heating and cooling of the dorsal fin and flukes affected temperatures at the countercurrent heat exchanger, but had little or no effect on temperatures posterior to its position. These measurements support the hypothesis that cooled blood is introduced into the deep abdominal cavity and functions specifically to regulate the temperature of arterial blood flow to the dolphin testes.     

Innervation of arteriovenous anastomoses in the brood patch of the domestic fowl

Summary The innervation of blood vessels in the brood patch (thoracic skin) of the domestic fowl was studied by use of the catecholamine fluorescence technique, acetylcholinesterase staining, and the immunoperoxidase technique for demonstration of vasoactive intestinal polypeptide (VIP). Large arteries and veins were sparsely innervated, whereas arteriovenous anastomoses (AVAs) were densely innervated by adrenergic, acetylcholinesterase-positive, and VIP-immunoreactive nerve fibres. The rich supply of different vasomotor nerves to AVAs emphasizes the importance of these vascular shunts in regulating blood flow and, in turn, the transport of heat to the brood patch. Furthermore, the presence of VIP-immunoreactive nerve fibres in the vasculature of the brood patch suggests that VIP might be the mediator of the previously reported cold-induced vasodilatation.     

Blood vessels and the occurrence of arteriovenous anastomoses in cephalic heat loss areas of mallards,Anas platyrhynchos (Aves)

Summary 1. The blood supply to cephalic heat loss areas (nasal and oropharyngeal mucosa, bill, eyelids) was studied in mallards by using plastic corrosion casts. The structure and organization of the blood vessels, as well as the occurrence of arteriovenous anastomoses (AVAs), were examined by scanning electron microscopy of vascular casts and by paraffin sections.2. Submucosal venous plexuses (cavernous tissue) are present in the nasal cavity, tongue, and lateral margins of the palate. These plexuses receive blood from post-capillary venules, but may also receive a non-nutritive component via numerous AVAs.3. High densities of AVAs were found in the eyelids and in the tip of the bill. In the tongue and nasal mucosa, the AVAs decreased in number caudally. The reason for regional differences in the density of AVAs is discussed in relation to variation in mechanical and thermal stimulation of the tissues.4. The connection of the different heat loss areas with the Rete ophthalmicum, which is a countercurrent heat exchanger important for brain cooling, is pointed out. The vascular pattern of the head suggests that sphincteric veins are involved in regulating the venous return from the evaporative surfaces of the nasal cavity and palate. One of these veins had, in addition to the normal circular smooth muscle fibres, a conspicuous component of longitudinally arranged, subendothelial, smooth muscle fibres.     

Arteriovenous anastomoses in the afferent region of trout gill filaments (Salmo gairdneri richardson,teleostei)

Summary Arteriovenous anastomoses (AVAs) in the afferent region of trout gill filaments originate from two small filament arteries (Fromm's arteries), which parallel the main afferent filament vessel on either side. As in the efferent filament arteries the origin of AVAs is bordered by specialized endothelial cells. Fromm's arteries originate from efferent filament or branchial arteries. A few extremely narrow connections between the afferent filament artery and Fromm's arteries (= afferent shunts) do exist in some gill filaments. Nevertheless, the AVAs in the afferent filament region carry mainly arterialized blood, or blood plasma, to the central venous sinus of the filament.Supported by the Deutsche Forschungsgemeinschaft (Vo 229/1)     

A laboratory exercise using a physical model for demonstrating countercurrent heat exchange

A physical model was used in a laboratory exercise to teach students about countercurrent exchange mechanisms. Countercurrent exchange is the transport of heat or chemicals between fluids moving in opposite directions separated by a permeable barrier (such as blood within adjacent blood vessels flowing in opposite directions). Greater exchange of heat or chemicals between the fluids occurs when the flows are in opposite directions (countercurrent) than in the same direction (concurrent). When a vessel loops back on itself, countercurrent exchange can occur between the two arms of the loop, minimizing loss or uptake at the bend of the loop. Comprehension of the physical principles underlying countercurrent exchange helps students to understand how kidneys work and how modifications of a circulatory system can influence the movement of heat or chemicals to promote or minimize exchange and reinforces the concept that heat and chemicals move down their temperature or concentration gradients, respectively. One example of a well-documented countercurrent exchanger is the close arrangement of veins and arteries inside bird legs; therefore, the setup was arranged to mimic blood vessels inside a bird leg, using water flowing inside tubing as a physical proxy for blood flow within blood vessels.     

Sympathetic activation increases basilar arterial blood flow in normotensive but not hypertensive rats

The close apposition between sympathetic and parasympathetic nerve terminals in the adventitia of cerebral arteries provides morphological evidence that sympathetic nerve activation causes parasympathetic nitrergic vasodilation via a sympathetic-parasympathetic interaction mechanism. The decreased parasympathetic nerve terminals in basilar arteries (BA) of spontaneously hypertensive rat (SHR) and renovascular hypertensive rats (RHR) compared with Wistar-Kyoto rats (WKY), therefore, would diminish this axo-axonal interaction-mediated neurogenic vasodilation in hypertension. Increased basilar arterial blood flow (BABF) via axo-axonal interaction during sympathetic activation was, therefore, examined in anesthetized rats by laser-Doppler flowmetry. Electrical stimulation (ES) of sympathetic nerves originating in superior cervical ganglion (SCG) and topical nicotine (10-30 μM) onto BA of WKY significantly increased BABF. Both increases were inhibited by tetrodotoxin, 7-nitroindazole (neuronal nitric oxide synthase inhibitor), and ICI-118,551 (β(2)-adrenoceptor antagonist), but not by atenolol (β(1)-adrenoceptor antagonist). Topical norepinephrine onto BA also increased BABF, which was abolished by atenolol combined with 7-nitroindazole or ICI-118,551. Similar results were found in prehypertensive SHR. However, in adult SHR and RHR, ES of sympathetic nerves or topical nicotine caused minimum or no increase of BABF. It is concluded that excitation of sympathetic nerves to BA in WKY causes parasympathetic nitrergic vasodilation with increased BABF. This finding indicates an endowed functional neurogenic mechanism for increasing the BABF or brain stem blood flow in coping with increased local sympathetic activities in acutely stressful situations such as the "fight-or-flight response." This increased blood flow in defensive mechanism diminishes in genetic and nongenetic hypertensive rats due most likely to decreased parasympathetic nitrergic nerve terminals.     

Development of arteriovenous anastomoses in the skin of the chicken and the influence of environmental temperature

Posthatching differentiation of arteriovenous anastomoses (AVAs) and the effect of heat exposure (38 degrees C) and cold acclimation (2-3 degrees C) on AVA density were studied in naked skin areas (eyelids, comb, wattles) of chickens. The AVAs were identifiable in the newly hatched chick, but they were extremely simple. The number of cell layers in the wall of the AVAs increased from two at hatching to four to five in the 5-month-old chickens. The density of the AVAs increased significantly during posthatching maturation. Cold acclimation of the chickens increased the density of AVAs by a factor of 2.1-3.2. Daily heat exposure also increased the density of AVAs significantly in the eyelids but had no effect in the other skin areas. Heat and cold had only minor effect on the vascularity of the skin; the only significant change recorded was a slight increase in the number of blood vessels in the wattles of the cold-acclimated chickens.     

The bleed off perfusion term in the Weinbaum-Jiji bioheat equation.

The microvascular organization and thermal equilibration of the primary and secondary arteries and veins that comprise the bleed off circulation to the muscle fibers from the parent countercurrent supply artery and veins are analyzed. The blood perfusion heat source term in the tissue energy equation is shown to be related to this vascular organization and to undergo a fundamental change in behavior as one proceeds from the more peripheral tissue, where the perfusion term is proportional to the Ta--Tv difference in the parent supply vessels, to the deeper tissue layers where the bleed off vessels themselves form a branching countercurrent system for each muscle tissue cylinder and the venous return temperature can vary between the local tissue temperature and Ta. The consequences of this change in behavior are examined for the Weinbaum-Jiji bioheat equation and a modified expression for the effective conductivity of perfused tissue is derived for countercurrent bleed off exchange.     

Mode of neural control mediating rat tail vasodilation during heating

The purpose of this investigation was to delineate the mode of efferent neural control mediating rat tail vasodilation during body heating. Tail blood flow (venous occlusion plethysmography), tail skin temperature over the ventral vascular bundle, and arterial pressure were measured in Sprague-Dawley rats anesthetized with pentobarbital sodium (45 mg/kg). Three protocols were followed: anesthesia of the lumbar sympathetic chain, bilateral lumbar sympathectomy, and sympathetic nerve stimulation during varying degrees of alpha-adrenergic receptor blockade. Mean tail blood flow and tail vascular conductance (TVC) during body heating were 40.3 +/- 8.7 ml X 100 ml-1 X min-1 and 39.2 +/- 9.2 ml X 100 ml-1 X min-1 X 100 mmHg-1, respectively. Interruption of sympathetic nerve activity by sympathetic nerve anesthetization or sympathectomy during heat stress caused a nonsignificant increase in TVC to 112.7 +/- 1.8 and 121.12 +/- 6.3%, respectively, of the values achieved with body heating. Sympathectomy performed in normothermic animals that had recovered from prior heating caused an increase in TVC to 128.4 +/- 14.0% of the levels achieved during the previous heating period. In addition, sympathetic nerve stimulation after complete alpha-adrenergic receptor blockade failed to produce a vasodilation [control TVC = 10.2 +/- 3.9 vs. TVC during nerve stimulation = 10.4 +/- 3.9 (P greater than 0.05)]. It is concluded that the increase in TVC during body heating occurs solely via a reduction in vasoconstrictor nerve activity.     

A new simplified bioheat equation for the effect of blood flow on local average tissue temperature

A new simplified three-dimensional bioheat equation is derived to describe the effect of blood flow on blood-tissue heat transfer. In two recent theoretical and experimental studies [1, 2] the authors have demonstrated that the so-called isotropic blood perfusion term in the existing bioheat equation is negligible because of the microvascular organization, and that the primary mechanism for blood-tissue energy exchange is incomplete countercurrent exchange in the thermally significant microvessels. The new theory to describe this basic mechanism shows that the vascularization of tissue causes it to behave as an anisotropic heat transfer medium. A remarkably simple expression is derived for the tensor conductivity of the tissue as a function of the local vascular geometry and flow velocity in the thermally significant countercurrent vessels. It is also shown that directed as opposed to isotropic blood perfusion between the countercurrent vessels can have a significant influence on heat transfer in regions where the countercurrent vessels are under 70-micron diameter. The new bioheat equation also describes this mechanism.     

Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries

Nitric oxide (NO) seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [³H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS) inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS) was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells) and Confocal Microscopy. Results indicated that: 1) in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A₁ receptors antagonist; 2) in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3) confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A₁ receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.     

Thermoregulation during swimming and diving in bottlenose dolphins, Tursiops truncatus

Heat transfer from the periphery is an important thermoregulatory response in exercising mammals. However, when marine mammals submerge, peripheral vasoconstriction associated with the dive response may preclude heat dissipation at depth. To determine the effects of exercise and diving on thermoregulation in cetaceans, we measured heat flow and skin temperatures of bottlenose dolphins (Tursiops truncatus) trained to follow a boat and to dive to 15 m. The results demonstrated that skin temperatures usually remained within 1 °C of the water after all exercise levels. Heat flow from peripheral sites (dorsal fin and flukes) increased over resting values immediately after exercise at the water surface and remained elevated for up to 20 min. However, post-exercise values for heat flow from the flukes and dorsal fin decreased by 30–67% when dolphins stationed at 15 m below the surface. The pattern in heat flow was reversed during ascent. For example, mean heat flow from the flukes measured at 5 m depth, 40.10 ± 2.47 W · m⁻², increased by 103.2% upon ascent. There is some flexibility in the balance between thermal and diving responses of dolphins. During high heat loads, heat transfer may momentarily increase during submergence. However, the majority of excess heat in dolphins appears to be dissipated upon resurfacing, thereby preserving the oxygen-conserving benefits of the dive response. Accepted: 4 January 1999     

Exertion-induced fatigue and thermoregulation in the cold

Cold exposure facilitates body heat loss which can reduce body temperature, unless mitigated by enhanced heat conservation or increased heat production. When behavioral strategies inadequately defend body temperature, vasomotor and thermogenic responses are elicited, both of which are modulated if not mediated by sympathetic nervous activation. Both exercise and shivering increase metabolic heat production which helps offset body heat losses in the cold. However, exercise also increases peripheral blood flow, in turn facilitating heat loss, an effect that can persist for some time after exercise ceases. Whether exercise alleviates or exacerbates heat debt during cold exposure depends on the heat transfer coefficient of the environment, mode of activity and exercise intensity. Prolonged exhaustive exercise leading to energy substrate depletion could compromise maintenance of thermal balance in the cold simply by precluding continuation of further exercise and the associated thermogenesis. Hypoglycemia impairs shivering, but this appears to be centrally mediated, rather than a limitation to peripheral energy metabolism. Research is equivocal regarding the importance of muscle glycogen depletion in explaining shivering impairments. Recent research suggests that when acute exercise leads to fatigue without depleting energy stores, vasoconstrictor responses to cold are impaired, thus body heat conservation becomes degraded. Fatigue that was induced by chronic overexertion sustained over many weeks, appeared to delay the onset of shivering until body temperature fell lower than when subjects were rested, as well as impair vasoconstrictor responses. When heavy physical activity is coupled with underfeeding for prolonged periods, the resulting negative energy balance leads to loss of body mass, and the corresponding reduction in tissue insulation, in turn, compromises thermal balance by facilitating conductive transfer of body heat from core to shell. The possibility that impairments in thermoregulatory responses to cold associated with exertional fatigue are mediated by blunted sympathetic nervous responsiveness to cold is suggested by some experimental observations and merits further study.     

Urocortin decreases phosphorylation of MYPT1 and increases the myosin phosphatase activity via elevation of the intracellular level of cAMP

Urocortin, a peptide hormone related to the corticotropin releasing factor, is suggested to be involved in blood pressure regulation by dilating the peripheral blood vessels. In rat tail arteries, urocortin-induced vasodilation is due to a decrease in myofilament Ca2+ sensitivity the mechanism of which is still unclear. In this study, the hypothesis was tested that the decrease in Ca2+ sensitivity in mouse tail arteries results from the activation of myosin light chain phosphatase. The relaxation of KCl-precontracted (42 mM) intact mouse tail arteries by urocortin (1 nM and 10 nM) was significantly inhibited by 1 microM antisauvagine30, a CRF-2 receptor antagonist (p < 0.05, n = 3). The addition of 1 microM KT 5720, an inhibitor of PKA, to intact rat tail arteries did not affect the KCl-induced force but significantly attenuated the urocortin-induced relaxation (n = 5). In alpha-toxin permeabilized mouse tail arteries, urocortin relaxed submaximally activated preparations at constant pCa 6.1 by 37.6 +/- 8.2% (n = 5) as compared to control vessels (n = 5, p < 0.001). The relaxation in permeabilized vessels was inhibited by pre-treatment with 30 microM Rp-8-CPT-cAMPS, an inactive analogue of cAMP. In permeabilized mouse tail arteries, treatment with 100 nM urocortin was associated with dephosphorylation of MLC20(Ser19) and MYPT1(Thr696/Thr850). The effect of urocortin on MYPTI dephosphorylation was completely abolished by 30 M Rp-8-CPT-cAMPS and mimicked by the cAMP analogue Sp-5,6-DCI-cBiMPS. Based on these findings, we propose that the urocortin-induced relaxation is due to a decrease in calcium sensitivity mediated by a cAMP-dependent increase in the activity of MLCP.     

Structural and functional characteristics of the special regulatory devices in the peripheral pulmonary circulation in rabbits

The present study intended to describe in detail the several blood vessels harboring special regulatory devices in rabbit’s pulmonary tissue using light and electron microscopy and immuno-histochemistry. Numerous throttle arteries were recorded within the adventitia of the segmental and sub-segmental bronchi and within pulmonary pleura. These arteries showed characteristic narrow or obliterated lumens and some of them bear longitudinal muscular intimal bolsters. For the first time, TEM revealed some structural modifications of the vascular endothelial cells of these arteries indicating that they become more activated to perform some additional functions. Arteriovenous anastomoses (AVAs) including direct shunt vessels and glomus organs were also recognized. Direct arteriovenous shunts appeared as small connecting devices communicating between small arteries and small veins while glomus organs consisted of the tortuous glomus vessels and the related afferent and efferent vessels. Several arteries and veins showing unique unusual structural characteristics were also described. For the first time, serotonin (5-HT) was strongly expressed in the vascular endothelium and muscle fibers of throttle arteries, in glomus cells of the glomus vessels, and in vascular endothelium of some veins and venules of special structure. The exact role of 5-HT is still unknown and further investigations are required to determine the types and distribution of 5-HT receptors present in these vascular devices. We concluded that these special vascular devices can play a critical role in controlling blood flow and pressure in the peripheral pulmonary circulation; however, the exact physiological mechanisms by which they work or are controlled remain unknown providing a ripe area for further investigation.     

Structure and sympathetic innervation of the intracranial arteries in the giraffe (Giraffa camelopardalis)

Fluorescence histochemistry discloses that the carotid rete mirabile in the giraffe has a poor sympathetic innervation. In contrast, the efferent artery of the rete (internal carotid artery) and the cerebral arteries show moderate sympathetic innervation. A certain degree of regional variability was noted in which the rostral arteries (anterior and middle cerebral) receive more sympathetic nerves than the caudal (posterior communicating and basilar) arteries. The sympathetic nerves on the giraffe cerebral vessels may constitute part of a host of mechanisms by which regional blood flow to the brain is regulated. Conversely, the paucity of sympathetic innervation of the carotid rete mirabile may indicate that this structure does not play an active role in vasoconstrictor responses during postural changes of the head.     

A subsidiary fever center in the medullary raphé?

In fever, as in normal thermoregulation, signals from the preoptic area drive both cutaneous vasoconstriction and thermogenesis by brown adipose tissue (BAT). Both of these responses are mediated by sympathetic nerves whose premotor neurons are located in the medullary raphé. EP3 receptors, key prostaglandin E2 (PGE2) receptors responsible for fever induction, are expressed in this same medullary raphé region. To investigate whether PGE2 in the medullary raphé might contribute to the febrile response, we tested whether direct injections of PGE2 into the medullary raphé could drive sympathetic nerve activity (SNA) to BAT and cutaneous (tail) vessels in anesthetized rats. Microinjections of glutamate (50 mM, 60-180 nl) into the medullary raphé activated both tail and BAT SNA, as did cooling the trunk skin. PGE2 injections (150-500 ng in 300-1,000 nl) into the medullary raphé had no effect on tail SNA, BAT SNA, body temperature, or heart rate. By contrast, 150 ng PGE2 injected into the preoptic area caused large increases in both tail and BAT SNA (+60 +/- 17 spikes/15 s and 1,591 +/- 150% of control, respectively), increased body temperature (+1.8 +/- 0.2 degrees C), blood pressure (+17 +/- 2 mmHg), and heart rate (+124 +/- 19 beats/min). These results suggest that despite expression of EP3 receptors, neurons in the medullary raphé are unable to drive febrile responses of tail and BAT SNA independently of the preoptic area. Rather, they appear merely to transmit signals for heat production and heat conservation originating from the preoptic area.     

The influence of the sympathetic innervation on the skin microvascular tone and blood flow oscillations

The influence of the sympathetic innervation on the tone of resistive vessels and blood flow oscillations was studied using laser Doppler flowmetry and skin thermography in 18 healthy subjects (before and after reflex cold and heat tests and local thermal testing), 42 patients with denervation syndromes caused by median nerve damage, and 10 patients with an acute stage of aseptic inflammation after radius fracture. The blood flow oscillations in the range of neurogenic sympathetic influences (0.02–0.052 Hz) supported by low-frequency sympathetic rhythms are an essential component of neurovascular interrelations. The importance of these oscillations is determined by their contribution to an increase in tissue perfusion owing to a decrease in the peripheral resistance and also by the leveling of drastic changes in blood flow and stabilization of microhemodynamics upon pronounced changes in the stationary tone. The high-and low-frequency (tonic and oscillatory, respectively) sympathetic rhythmic activities are expressed in two ways: (1) a synchronous increase or decrease in their amplitudes and (2) frequency dominance. The reactivity of the vessel smooth muscles is an important factor in maintaining the blood flow oscillations. Denervation decreases the oscillation amplitude in the neurogenic range. Under the conditions of local “inflammatory sympatholysis,” reflex tonic effects, rather than oscillatory ones, of the sympathetic impulses are mainly suppressed. An isolated evaluation of the blood flow oscillations in the neurogenic sympathetic range cannot be a measure of sympathetic activity. In studies on its functional state and evaluation of the neurogenic tone (NT) of resistive vessels, it is necessary to take into account the parameters of both stationary and oscillatory components of the NT.     

Noninvasive assessment of sympathetic vasoconstriction in human and rodent skeletal muscle using near-infrared spectroscopy and Doppler ultrasound.

The precise role of the sympathetic nervous system in the regulation of skeletal muscle blood flow during exercise has been challenging to define in humans, partly because of the limited techniques available for measuring blood flow in active muscle. Recent studies using near-infrared (NIR) spectroscopy to measure changes in tissue oxygenation have provided an alternative method to evaluate vasomotor responses in exercising muscle, but this approach has not been fully validated. In this study, we tested the hypothesis that sympathetic activation would evoke parallel changes in tissue oxygenation and blood flow in resting and exercising muscle. We simultaneously measured tissue oxygenation with NIR spectroscopy and blood flow with Doppler ultrasound in skeletal muscle of conscious humans (n = 13) and anesthetized rats (n = 9). In resting forearm of humans, reflex activation of sympathetic nerves with the use of lower body negative pressure produced graded decreases in tissue oxygenation and blood flow that were highly correlated (r = 0.80, P < 0.0001). Similarly, in resting hindlimb of rats, electrical stimulation of sympathetic nerves produced graded decreases in tissue oxygenation and blood flow velocity that were highly correlated (r = 0.93, P < 0.0001). During rhythmic muscle contraction, the decreases in tissue oxygenation and blood flow evoked by sympathetic activation were significantly attenuated (P < 0.05 vs. rest) but remained highly correlated in both humans (r = 0.80, P < 0.006) and rats (r = 0.92, P < 0.0001). These data indicate that, during steady-state metabolic conditions, changes in tissue oxygenation can be used to reliably assess sympathetic vasoconstriction in both resting and exercising skeletal muscle.