Projects per year
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.
|Number of pages||8|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Publication status||Published - 15 May 2015|
Arterial stiffness: mechanistic role of interaction of cellular processes with the extracellular matrix
Avolio, A., Graham, R., Berkowitz, D., MQRES, M., Chinchen, G. & PhD Contribution (ARC), P. C. (.
1/01/11 → 30/04/15