Flow-Mediated Vascular Remodeling in Hypertension

Abstract

Changes in shear and medial wall stress induced by blood flow contribute to vascular remodeling, but details of these relations remain undefined. We hypothesized that remodeling has a strong genetic component and that phenotypic responses to hemodynamic stress will differ among rat strains. Here, we characterized phenotypic traits related to carotid remodeling in the 2 rat strains that we previously showed the greatest difference in shear stress regulation: Genetically Hypertensive (GH) and Brown Norway (BN) rat strains. Left internal and external carotid arteries were ligated and blood flow was reduced in the left common (LCA) by 90% and increased in the right common carotid artery (RCA) by 60%. Rats were studied for up to 28 days after flow modification and carotid outer diameters were measured in vivo, and wall and luminal components by histomorphometry, to obtain indices of remodeling. Blood flow and pressure measurements were made at corresponding time points. By day 28, remodeling in the GH was greater in response to high flow than in BN, and shear stress was normalized. In contrast, remodeling in the BN was greater in the low flow LCA than in GH. Media stress was greater in GH than BN for any value of carotid shear stress and remained relatively unchanged in low flow, but markedly increased in high flow remodeling. Importantly, pressure was not a major determinant of flow remodeling in these conditions. There are key differences in the ability of carotids in GH and BN rats to adhere to hemodynamic laws during vascular remodeling. GH rats exhibit intact regulatory mechanisms for increased, but not reduced, shear stress. Moreover, the ability to maintain physiological shear and media stresses during vascular remodeling in response to modified flow appears to be intrinsically "genetically" determined.