The capacity for myocardial perfusion depends on the coronary microvascular structure. Coronary microvessels may adapt their structure to various stimuli. We tested whether the local pressure profile affects tone and remodeling of porcine coronary microvessels. Sub-endocardial vessels (~160 µm, n=53) were cannulated and kept in organoid culture for 3 days under different transvascular pressure profiles: Osc80: mean 80 mmHg, 60 mmHg peak-peak sine wave pulsation amplitude at 1.5 Hz; St80: steady 80 mmHg; Osc40: mean 40 mmHg, 30 mmHg amplitude; St40: steady 40 mmHg. Under the Osc80 profile, modest tone developed, reducing the diameter to 81±14% (SEM, n=6) of the maximal, passive diameter. No inward remodeling was found here, as determined from the passive pressure-diameter relation after 3 days of culture. Under all other profiles, much more tone developed (e.g. Osc40: to 26±3%, n=7). In addition, these vessels showed eutrophic (i.e. without a change in wall cross-sectional area) inward remodeling (e.g. Osc40: passive diameter reduction by 24±3%). The calcium blocker, amlodipine induced maintained dilation in St40 vessels, and reversed the 22±3% (n=6) inward remodeling to 15±3% (n=8) outward remodeling towards day 3. Vessels required a functional endothelium in order to maintain structural integrity in culture. Our data indicate that reduction of either mean pressure or pulse pressure leads to microvascular constriction followed by inward remodeling. These effects could be reversed by amlodipine. While microvascular pressure profiles distal to stenoses are poorly defined, these data suggest that vasodilator therapy could improve sub-endocardial microvascular function and structure in coronary artery disease.