Arterial Function and Flow Related Arterial Remodeling during DOCA‐salt Hypertension

Abstract

HypothesisThe DOCA‐salt Hypertensive rat (DOCA), a model of enhanced function of endothelin‐1 (ET‐1), displays: 1. Increased importance of endogenous ET‐1 in vasoreactivity 2. Altered flow‐related arterial remodeling.Methods1. 2nd order rat mesenteric artery (MrA) reactivity was assessed using wire‐myography. 2. Flow modifying surgery was performed as described by Pourageaud and De Mey (1997) and arteries were analysed by pressure arteriography and histology.Results1. the endothelin‐receptor antagonist Bosentan endothelium‐dependently reduced contractile responses to K+‐induced depolarization in arteries of DOCA but not SHAM. 2. No outward hypertrophic remodeling occurred in high flow (HF) arteries of DOCA. Arteries exposed to low flow (LF) conditions, showed inward remodeling, hypertrophy, and infiltration of ED‐1 (monocyte/macrophage‐marker) positive cells. DOCA MrA's showed a marked reduction in calculated distensibility. α‐Smooth muscle actin staining of LF vessels showed development of “collaterals” in the adventitia.ConclusionDOCA MrA's show increased contribution of endogenous ET‐1 to K+‐induced vasomotor responses, impaired outward remodeling, arterial stiffening and hypertrophy. LF MrA's show infiltration of inflammatory cells and development of “collaterals” in the adventitia.This study was performed within project T2–108 of the Dutch Top Institute Pharma.