Pressure dependency of aortic pulse wave velocity in vivo is not affected by vasoactive substances that alter aortic wall tension ex vivo

Abstract

Aortic stiffness, a predictive parameter in cardiovascular medicine, is blood pressure dependent and experimentally requires isobaric measurement for meaningful comparison. Vasoactive drug administration to change peripheral resistance and blood pressure allows such isobaric comparison but may alter large conduit artery wall tension, directly changing aortic stiffness. This study quantifies effects of sodium nitroprusside (SNP, vasodilator) and phenylephrine (PE, vasoconstrictor) on aortic stiffness measured by aortic pulse wave velocity (aPWV) assessed by invasive pressure catheterization in anaesthetized Sprague-Dawley rats (n = 7). This was compared with nondrug-dependent alteration of blood pressure through reduced venous return induced by partial vena cava occlusion. In vivo drug concentration was estimated by modeling clearance rates. Ex vivo responses of excised thoracic and abdominal aortic rings to drugs was measured using myography. SNP administration did not alter aPWV compared with venous occlusion (P = 0.21-0.87). There was a 5% difference in aPWV with PE administration compared with venous occlusion (P < 0.05). The estimated in vivo maximum concentration of PE (7.0 ± 1.8 ×10(-7) M) and SNP (4.2 ± 0.6 ×10(-7) M) caused ex vivo equivalent contraction of 52 mmHg (thoracic) and 112 mmHg (abdominal) and relaxation of 96% (both abdominal and thoracic), respectively, despite having a negligible effect on aPWV in vivo. This study demonstrates that vasoactive drugs administered to alter systemic blood pressure have a negligible effect on aPWV and provide a useful tool to study pressure-normalized and pressure-dependent aPWV in large conduit arteries in vivo. However, similar drug concentrations affect aortic ring wall tension ex vivo. Future studies investigating in vivo and ex vivo kinetics will need to elucidate mechanisms for this marked difference.

A novel set‐up for the ex vivo analysis of mechanical properties of mouse aortic segments stretched at physiological pressure and frequency

“…; Butlin et al . ) and here we confirm that it provides a sufficiently sensitive and practical method to estimate transluminal pressure to evaluate the effects of distension pressure and VSMC tone. Secondly, perfusion‐based set‐ups expose the endothelial cells to shear stress, a well‐known stimulator of endothelial NO production.…”

“…A study that compared the effects of vasoactive substances on the aorta found large differences in vivo versus ex vivo (Butlin et al . ) and visco‐elastic properties of the aorta change significantly after isolation of the aorta from the animal (Boutouyrie et al . ).…”

Tissue Transglutaminase Modulates Vascular Stiffness and Function Through Crosslinking‐Dependent and Crosslinking‐Independent Functions

“…In vivo vascular stiffness was examined by obtaining invasive PWV measurements at mean arterial pressures varying from 55 to 130 mm Hg as previously described . We used a high‐fidelity dual‐pressure catheter sensor to measure aortic PWV.…”

Isometric Stretch Alters Vascular Reactivity of Mouse Aortic Segments

“…In mouse aortic segments, implemented preloads are highly variable among different studies and range from about 1.2–8.0 mN/mm (Fransen et al, 2008, 2015; Van Hove et al, 2009; Ponnoth et al, 2012; van Langen et al, 2012; Lloyd et al, 2013; Taguchi et al, 2014; Gross et al, 2015; Leloup et al, 2015a; Zhou et al, 2015). According to Laplace's law, and assuming a thin, isotropic and homologous wall for large vessels such as the aorta, the transmural pressure (P, in mm Hg) is directly proportional to the preload (PL, in mN) and inversely proportional to its length (l, in mm) and radius (r, in mm): P = PL/(l × 2r) × 7.5) (Syyong et al, 2009; Van Herck et al, 2009; Butlin et al, 2015). Preloads between 1.2 and 8.0 mN/mm roughly correlate with transmural pressures from 10 to 65 mmHg and are sub-physiological.…”