Exploring the Vascular Smooth Muscle Receptor Landscape In Vivo: Ultrasound Doppler versus Near Infrared Spectroscopy (NIRS) Assessments

Stephen J. Ives, Paul J. Fadel, R. Matthew Brothers, Mikael Sander, D. Walter Wray


Ultrasound Doppler and near infrared spectroscopy (NIRS) are routinely used for non-invasive 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 pharmacologic manipulation of vascular smooth muscle receptors located at varied locations within the arterial tree is unknown. Thus, in ten healthy subjects (25±2 yrs), changes in resting leg blood flow (Ultrasound Doppler; femoral artery) and muscle oxygenation (HbO2+MbO2; vastus lateralis) were evaluated simultaneously in response to intra-arterial infusions of phenylephrine (PE, 0.025 - 0.8 μg/kg/min), BHT-933 (2.5 - 40 µg/kg/min), and angiotensin II (ANGII, 0.5 - 8 ng/kg/min). All drugs elicited significant dose-dependent reductions in leg blood flow and HbO2+MbO2. Significant relationships were found between ultrasound Doppler and NIRS changes across doses of PE (r2 = 0.37±0.08), BHT-933 (r2 = 0.74±0.06), and ANGII (r2 = 0.68±0.13), with the strongest relationships evident with agonists for receptors located preferentially "downstream" in the leg microcirculation (BHT-933 and ANGII). 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 ANGII (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.

  • vascular imaging
  • alpha adrenergic
  • ANG-II
  • vasoconstriction
  • microcirculation