Effect of neurogenic blockade on viscoelastic properties of large arteries in polycystic kidney disease rats Zahra (Parisa) Kouchaki, George Lindesay, Mark Butlin, Jacqueline K Phillips, Alberto P Avolio. Australian School of Advanced Medicine, Macquarie University, Sydney, Australia. Introduction • Arterial stiffness is determined by load-bearing wall components (elastin, collagen) that determine passive wall elastic properties. • However, changes in tone of smooth muscle cells mediated by neurogenic effects can affect normalised wall viscoelasticity (η n ), manifest as phase changes between time-varying signals of pressure (P (t )) and diameter (D (t )) 1 . • The aim of this study was to characterize the neurogenic ef- fects on n of large arteries in rat models of altered arterial stiffness (Lewis Polycystic Kidney (LPK) disease rats and Lewis controls) 2 . Methods • Intravascular pressure (Scisence catheter) and diameter (ul- trasound, Artlab) were measured in the abdominal aorta of anaesthetised (urethane, 1.3 g/kg): • Lewis rats (n=11), and • LPK rats (n=5) • In each case, measurements were taken before and after neu- rogenic blockade by intravenous hexamethonium (20 mg/kg). • Vasoactive agents (6 μg phenylephrine or sodium nitroprusside, intravenous bolus) were used to alter mean arterial pressure (MAP) to quantify relationships between P (t ) and D (t ) signals and MAP. time (s) 0.00 0.05 0.10 0.15 0.20 0.25 0.30 80 90 100 110 120 aortic pressure (mmHg) 1080 1120 1160 1200 aortic diameter (μm) 80 90 100 110 120 1080 1120 1160 1200 aortic pressure (mmHg) aortic diameter (μm) systole diastole Figure 1 : The aortic pressure and diameter pulse (top) during a single car- diac cycle. The lag between pressure and diameter (as indicated by the loop, bottom) is related to the viscoelasticty of the vessel. The viscoelasticity was quantified by the phase lag of diameter and pressure over the first three Fourier harmonics, as described in Equation 1 and 2 • For a MAP of 75, 100, 125, and 150 mmHg, complex elastic modulus (E (ω )) was determined as the ratio of the Fourier (fft harmonics ω i , i =1, 2. . . n) components of P (t ) and D (t ) for each cardiac cycle (Equation 1). • The viscoelasticity (η n ) was calculated from the ratio of the imag- inary part of E (ω ) to the harmonic frequency (ω i ), averaged across the first three harmonics (Equation 2; i =1-3). E (ω )= fft (P (t )) fft (D (t )) (1) η ni = Im[E (ω i )]/ω i , i = 1 - 3 (2) Results • Viscoelasticity (η n ) increased with frequency in all but Lewis rats at 150 mmHg. • LPK rats had higher viscoelasticity than Lewis rats (p<0.05), other than denervated rats at a MAP of 150 mmHg and intact rats at 75 mmHg. • Neurogenic blockade reduced viscoelasticity in both LPK and Lewis groups (p<0.05). • Viscoelasticity increased with pressure (p<0.001). 75 100 125 150 MAP (mmHg) viscoelasticity (x10 -3 mmHg ⋅ s mm) 0 1 2 3 4 5 6 Lewis neurogenic blockade Lewis intact LPK neurogenic blockade LPK intact Figure 2 : Vicscoelasticty showing increase with pressure, and differences be- tween LPK and control rats, and with neurogenic blockade. Error bars indicate ± standard deviation. Conclusions • Viscoelasticity of the arterial wall is affected by MAP as well as smooth muscle tone due to neurogenic input. • Neurogenic modulation of wall viscoelasticity is more pro- nounced in stiffer vessels. • Aortic viscoelasticty was generally greater in LPK rats and was reduced with neurogenic blockade. • This study shows possible relationships between aortic compli- ance in polycystic kidney disease and sympathetic dysregula- tion. References: 1 Valdez-Jasso D, Bia D, Zcalo Y, Armentano RL, Haider MA, Olufsen MS. Linear and nonlinear viscoelastic modeling of aorta and carotid pressure-area dynamics under in vivo and ex vivo conditions. Ann Biomed Eng. May;39(5):1438-1456, 2011. 2 Ng K, Hildreth CM, Phillips JK, Avolio AP. Aortic stiffness is associated with vascular calci- fication and remodeling in a chronic kidney disease rat model. Am J Physiol Renal Physiol. 300(6):F1431-1436, 2011. www.medicine.mq.edu.au parisa.kouchaki@students.mq.edu.au