How Structure, Mechanics, and Function of the Vasculature Contribute to Blood Pressure Elevation in Hypertension.

Large conduit arteries and the microcirculation participate in the mechanisms of elevation of blood pressure (BP). Large vessels play roles predominantly in older subjects, with stiffening progressing after middle age leading to increases in systolic BP found in most humans with aging. Systolic BP elevation and increased pulsatility penetrate deeper into the distal vasculature, leading to microcirculatory injury, remodelling, and associated endothelial dysfunction. The result is target organ damage in the heart, brain, and kidney. In younger individuals genetically predisposed to high BP, increased salt intake or other exogenous or endogenous risk factors for hypertension, including overweight and excess alcohol intake, lead to enhanced sympathetic activity and vasoconstriction. Enhanced vasoconstrictor responses and myogenic tone become persistent when embedded in an increased extracellular matrix, resulting in remodelling of resistance arteries with a narrowed lumen and increased media-lumen ratio. Stimulation of the renin-angiotensin-aldosterone and endothelin systems and inflammatory and immune activation, to which gut microbiome dysbiosis may contribute as a result of salt intake, also participate in the injury and remodelling of the microcirculation and endothelial dysfunction. Inflammation of perivascular fat and loss of anticontractile factors play roles as well in microvessel remodelling. Exaggerated myogenic tone leads to closure of terminal arterioles, collapse of capillaries and venules, functional rarefaction, and eventually to anatomic rarefaction, compromising tissue perfusion. The remodelling of the microcirculation raises resistance to flow, and accordingly raises BP in a feedback process that over years results in stiffening of conduit arteries and systo-diastolic or predominantly systolic hypertension and, more rarely, predominantly diastolic hypertension. Thus, at different stages of life and the evolution of hypertension, large vessels and the microcirculation interact to contribute to BP elevation.