title: Exploring the vascular smooth muscle receptor landscape in vivo: ultrasound Doppler versus near-infrared spectroscopy assessments.
abstract: Ultrasound Doppler and near-infrared spectroscopy (NIRS) are routinely used for noninvasive monitoring of peripheral hemodynamics in both clinical and experimental settings. However, the comparative ability of these methodologies to detect changes in microvascular and whole limb hemodynamics during pharmacological manipulation of vascular smooth muscle receptors located at varied locations within the arterial tree is unknown. Thus, in 10 healthy subjects (25 ± 2 yr), changes in resting leg blood flow (ultrasound Doppler; femoral artery) and muscle oxygenation (oxyhemoglobin + oxymyoglobin; vastus lateralis) were simultaneously evaluated in response to intra-arterial infusions of phenylephrine (PE, 0.025-0.8 μg·kg(-1)·min(-1)), BHT-933 (2.5-40 μg·kg(-1)·min(-1)), and angiotensin II (ANG II, 0.5-8 ng·kg(-1)·min(-1)). All drugs elicited significant dose-dependent reductions in leg blood flow and oxyhemoglobin + oxymyoglobin. Significant relationships were found between ultrasound Doppler and NIRS changes across doses of PE (r(2) = 0.37 ± 0.08), BHT-933 (r(2) = 0.74 ± 0.06), and ANG II (r(2) = 0.68 ± 0.13), with the strongest relationships evident with agonists for receptors located preferentially "downstream" in the leg microcirculation (BHT-933 and ANG II). Analyses of drug potency revealed similar EC50 between ultrasound Doppler and NIRS measurements for PE (0.06 ± 0.02 vs. 0.10 ± 0.01), BHT-933 (5.0 ± 0.9 vs. 4.5 ± 1.3), and ANG II (1.4 ± 0.8 vs. 1.3 ± 0.3). These data provide evidence that both ultrasound Doppler and NIRS track pharmacologically induced changes in peripheral hemodynamics and are equally capable of determining drug potency. However, considerable disparity was observed between agonist infusions targeting different levels of the arterial tree, suggesting that receptor landscape is an important consideration for proper interpretation of hemodynamic monitoring with these methodologies.
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah;
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fadel
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Brothers
authors.forename: Mikael
authors.initials: M
authors.lastname: Sander
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage; D001158:Arteries / Q000000981:diagnostic imaging / Q000378:metabolism; D001381:Azepines / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007261:Infusions, Intra-Arterial; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D010108:Oxyhemoglobins / Q000378:metabolism; D010656:Phenylephrine / Q000008:administration & dosage; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D019265:Spectroscopy, Near-Infrared; D018608:Ultrasonography, Doppler; D055815:Young Adult
chemical_list: D000316:Adrenergic alpha-Agonists; D001381:Azepines; D015415:Biomarkers; D009211:Myoglobin; D010108:Oxyhemoglobins; D011942:Receptors, Adrenergic, alpha; D011945:Receptors, Angiotensin; C017595:oxymyoglobin; D000804:Angiotensin II; D010656:Phenylephrine; C015603:azepexole
keywords: angiotensin II; microcirculation; vascular imaging; vasoconstriction; α-adrenergic