CHRONIC ALPHA(1)-ADRENERGIC BLOCKADE STIMULATES TERMINAL AND ARCADE ARTERIOLAR DEVELOPMENT

The arteriolar network undergoes structural adaptation in several phys iological and pathological conditions, including exercise, maturation, hypertension, and reduced tissue perfusion due to arterial ligation. Although many physical and biochemical stimuli for arteriolar adaptati on have been proposed, the individual contributions of these specific stimuli have yet to be elucidated. We tested the hypothesis that hemod ynamic stress is an important determinant of growth and remodeling in the arteriolar network. An immunofluorescence, dual-labeling technique for the smooth muscle (SM) contractile proteins SM alpha-actin and SM myosin heavy chain (MHC) was used to assess terminal and arcade arter iolar (AA) remodeling in the rat gracilis muscle arteriolar network in response to chronic vasodilation, a stimulus that elevates circumfere ntial wall stress levels in the arterioles and capillaries. SM oc-acti n, a marker of SM from the earliest stages of differentiation, was use d to delineate the terminal and AAs. SM-MHC, a marker of SM in later s tages of differentiation, was used to assess the relative maturity sta te of SM. in terminal arteriolar endings. Mean percentage of SM-MHC ne gative terminal arteriolar endings per muscle, a measure of terminal a rteriolar development, increased from 37.6 to 56.0% after 1 wk of praz osin treatment and from 36.3 to 57.6% after 2 wk of treatment. Mean nu mber of AA segments with diameters <15 mu m increased more than threef old from 1.25 to 5.25 after 2 wk, consistent with the formation of new AA segments by the anastomoses of small-diameter terminal arterioles. Because arteriolar remodeling proceeded in a network pattern that has been shown to be consistent with a circumferential wall stress-growth rule and inconsistent with a wall shear stress-growth rule, the exper imental results suggest that circumferential wall stress is a stimulus for arteriolar network remodeling.