 1 -Adrenergic-receptor responsiveness in skeletal muscle during dynamic exercise JOHN B. BUCKWALTER, PATRICK J. MUELLER, AND PHILIP S. CLIFFORD Departments of Anesthesiology and Physiology, Medical College of Wisconsin and Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295 Buckwalter, John B., Patrick J. Mueller, and Philip S. Clifford.  1 -Adrenergic-receptor responsiveness in skel- etal muscle during dynamic exercise. J. Appl. Physiol. 85(6): 2277–2283, 1998.—Attenuation of sympathetic vasoconstric- tion (sympatholysis) in working muscles during dynamic exercise is controversial. One potential mechanism is a reduction in  1 -adrenergic-receptor responsiveness. The pur- pose of this study was to examine  1 -adrenergic-receptor- mediated vasoconstriction in resting and working skeletal muscles by using intra-arterial infusions of a selective ago- nist. Seven mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. A selective  1 -adrenergic- receptor agonist (phenylephrine) was infused as a bolus into the femoral artery catheter at rest and during exercise. All dogs ran on a motorized treadmill at two exercise intensities (3 and 6 miles/h). Intra-arterial infusions of the same effective concentration of phenylephrine elicited reductions in vascu- lar conductance of 76  4, 76  6, and 67  5% (P  0.05) at rest, 3 miles/h, and 6 miles/h, respectively. Systemic blood pressure and blood flow in the contralateral iliac artery were unaffected by phenylephrine. These results do not demon- strate an attenuation of vasoconstriction to a selective  1 - agonist during exercise and do not support the concept of sympatholysis. blood flow; sympatholysis; autonomic nervous system; phenyl- ephrine; dogs AT THE ONSET OF EXERCISE there is a substantial increase in blood flow to active skeletal muscle. This skeletal muscle hyperemia reflects an increased demand for oxygen in active skeletal muscle. The ability of the sympathetic nervous system to restrict blood flow to these working muscles is controversial. A number of studies have shown that sympathetic blockade has no effect on blood flow in active skeletal muscle (5, 8, 17, 19). On the other hand, other studies have clearly demonstrated the ability of the sympathetic nervous system to restrict blood flow in active skeletal muscle (2, 13, 27, 30, 37). An attenuation of vasoconstriction in the arterial vasculature of skeletal muscle during muscle contraction has been reported by a number of investigators (3, 14, 15, 31, 32, 36). This diminished vascular responsiveness to sympathetic stimulation during muscular contraction was termed ‘‘sympatholy- sis’’ by Remensnyder et al. (31). The purpose of this study was to examine exercise- induced alterations in  1 -adrenergic-receptor respon- siveness in the vasculature of skeletal muscle. We used an experimental approach that allowed examination of  1 -adrenergic-receptor responsiveness in one hindlimb at rest and during exercise while not affecting systemic hemodynamics in a conscious dog. We hypothesized that  1 -adrenergic-receptor-mediated vasoconstriction to an intra-arterial bolus of a selective  1 -agonist would be attenuated from rest to exercise in an exercise- intensity-dependent manner. METHODS AND PROCEDURES All experimental procedures were approved by the Institu- tional Animal Care and Use Committee and were conducted in accordance with the American Physiological Society’s Guiding Principles in the Care and Use of Animals. Mongrel dogs were selected for their willingness to run on a motorized treadmill and were instrumented in a series of sterile surgical procedures. Anesthesia was induced with thiopental sodium (15–30 mg/kg; Gensia Pharmaceuticals, Irvine, CA). After intubation with a cuffed endotracheal tube, a surgical level of anesthesia was maintained through mechanical ventilation with 1.5% halothane (Halocarbon Laboratories, River Edge, NJ) and 98.5% oxygen. Antibiotics (cefazolin sodium, Apoth- econ, Princeton, NJ) and analgesic drugs (buprenorphine hydrochloride, 0.3 mg; Reckitt and Coleman, Kingston-upon- Hull, UK) were given postoperatively. During the first surgi- cal procedure, the carotid arteries were placed in skin tubes in the neck so that they could be cannulated percutaneously to measure arterial blood pressure (23, 24). In the second surgery, all dogs were instrumented with flow probes (4- or 6-mm ultrasonic transit-time flow probes, Transonic Systems, Ithaca, NY) around the external iliac artery to each hindlimb to measure blood flow. The cables were then tunneled under the skin to the back. The dogs were given 2 wk to recover from flow probe implantation. In the final surgery, a heparinized catheter (0.045-in. OD, 0.015-in. ID, 60-cm length, Data Science International, St. Paul, MN) for drug infusion was implanted chronically through a side branch into the femoral artery and tunneled to the back of the dog. To maintain patency, the catheter was flushed daily with saline and filled with a heparin solution (100 IU heparin/ml in 50% dextrose solution). The dogs were given at least 2 days to recover from the final surgery before any experiments were performed. All experiments were performed in a laboratory in which the temperature was maintained below 20°C. A 20-gauge Teflon catheter (Insyte, Becton-Dickinson, Deseret, Sandy, UT) was inserted retrogradely into the lumen of the carotid artery and attached to a solid-state pressure transducer (Ohmeda, Madison, WI). The flow probes were connected to a transit-time flowmeter (Transonic Systems). In all experi- ments, the dogs ran on the treadmill at two different intensi- ties: 3 miles/h (4.8 km/h), 0% grade and 6 miles/h (9.7 km/h), 0% grade. Series 1. Six dogs weighing between 16 and 21 kg received a bolus of 25 μg of phenylephrine, a selective  1 -agonist (Ameri- can Regent Laboratories, Shirley, NY), into one hindlimb at rest, during steady-state exercise, and postexercise. The dogs The costs of publication of this article were defrayed in part by the payment of page charges. 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