Abstract P3004: Brain Microvascular Structure During Hypertension: Temporal Changes and Recovery Support Distinct Arteriolar Mechanisms

Abstract

Hypertension alters vascular structure including diameter, cross-sectional area (CSA), and stiffness of the vessel wall. Inward remodeling is a feature of small vessel disease (SVD), predictive of vascular events and cognitive decline. While effects of prevention of hypertension on large arteries have been studied widely, quantification of temporal changes and recovery from hypertension in microvessels is rare. Previously, angiotensin II (Ang II)-dependent hypertension produced increased CSA but reduced internal diameter (ID) of maximally dilated arterioles (inward remodeling) in brain. Because cerebral arterioles are targets of SVD, we examined time course and whether microvessels recover from hypertension. Mean arterial pressure (MAP) was measured using radiotelemetry in adult male C57BL6J mice prior to, during infusion of vehicle or Ang II (1.4 mg/kg per day using osmotic mini-pumps) for 28 days, and a 28 day recovery period. Prior to treatment, MAP was similar in both groups. Throughout recording, MAP was stable in vehicle treated mice. With Ang II, MAP began to rise on day 3, steadily increasing until day 28. On day 30, MAP began to decrease, reaching levels seen with vehicle on days 46-47. In anesthetized mice, we measured pressure, diameter, and CSA of the vessel wall (histologically) in maximally dilated arterioles (baseline diameter of 63±1 microns) at 1, 3, 7, 14, 28, and 56 days after pump implantation (n=7-9 in each group). At day 1, ID and CSA were similar in both groups. With vehicle, there was no significant change in CSA or ID at any time point. With Ang II, CSA increased at day 7 and was maintained at days 14 and 28 (P=0.023). ID did not change at day 3 or 7, but was reduced (by ~15%, P=0.011) at 14 and 28 days. During recovery (day 56). CSA returned 63% of the way to normal (compared to vehicle), while ID remained at day 14 and 28 values. In conclusion, CSA changed rapidly during hypertension onset and largely recovered with a reduction in MAP. Inward remodeling developed slowly and did not return to vehicle levels with MAP. The lack of recovery of ID after a period of hypertension has implications for the impact of SVD including hypoperfusion, impaired vasodilation, and augmented injury during ischemia.