(E-181) Early remodeling of the first order mesenteric artery in an adipose-driven model of hypertension

Introduction:: Prior research shows that the remodeling of muscular arteries, such as mesenteric arteries, plays an important role in an angiotensin II model of hypertension (Mutada et al.). It is also known that mesenteric arteries are crucial in regulating peripheral resistance and, in turn, systemic blood pressure (Christensen et al.). It is still unknown, however, if remodeling of mesenteric arteries is present in an adipose-driven model of hypertension. In this study we aim to characterize early remodeling of first order mesenteric arteries in a Dahl Salt Sensitive rat model of hypertension, as it is related to high fat diet.

Materials and Methods:: We quantified the mechanical behavior of the first order mesenteric artery of the male Dahl Salt Sensitive rat at 8 weeks old on control (CD, n=4) and high fat (HF, n=4) diets via pressurization tests. After tissue isolation, we cannulated the vessels in a pressure arteriograph chamber (Instrumentation and Modeling Facility, University of Vermont, Burlington, VT) and estimated the axial length that prevented buckling for an inner pressure of 60 mmHg. The arteries were tested in calcium containing HEPES buffer heated to ~36°C for luminal pressures increasing from 20 to 120 mmHg in 20 mmHg increments while tracking the inner and outer diameter. The 20-mmHg luminal pressure was held for 20 minutes to allow for equilibration and each subsequent step was held for at least 5 minutes. The heat was then turned off and 1mM of EGTA + calcium free HEPES buffer was circulated through the chamber and arteries were tested at pressures decreasing from 120 to 20 mmHg in 20 mmHg increments (Fig 1a). We calculated the stress-stretch curve from the pressure-diameter measurements (Fig 1b-c respectively). Stress was calculated using the law of Laplace for a thin-walled, cylindrical, pressurized vessel. We defined stress as the mid-wall radius recorded for each value of pressure divided by the mid-wall radius at 60 mmHg (i.e., in vivo condition, Enori et al., Fenger-Gron et al.).



Results, Conclusions, and Discussions:: This study aimed to characterize early remodeling in the first order mesenteric artery of an animal model of high fat driven hypertension. While none of the metrics show significant difference, we identified some trends worth discussing. The HF-diet samples show a trend toward rightward shift on the pressure-diameter curve and upward shift on the stress-strain curve (both not significant, Fig. 1 b-c). The lumen diameter, arterial wall thickness, stress, and stiffness were compared (Fig. 1d-f) at an intraluminal pressure of 60 mmHg due to its physiological importance (Enori et al., Fenger-Gron et al.). There is a trend toward increased lumen diameter and circumferential wall stress in the arteries collected from animals fed a HF-diet when compared to the CD. Taken together these results suggest a trend toward increasing stiffness (not significant) in the HF-diet animals. It is important to notice that the mean arterial pressure was slightly, but significantly higher in HFD animals (133.92±1.61 mmHg) compared to CD animals (122.39±3.28 mmHg), while we did not record a significant change for the systolic pressure.

We found no significant changes in the mechanics of first order mesenteric arteries, associated with early remodeling in an adipose-driven model of hypertension. However, we did identify trends (increased lumen and wall stress in HFD compared to CD) that could become significant in later time points. We also plan to quantify wall structural and compositional changes through a histological study.


Acknowledgements (Optional): : This work was supported by Michigan State University Internal Funds; National Heart, Lung, and Blood Institute Grant P01HL152951 (to S.W.W.).

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