Calcium channel blockade prevents pressure-dependent inward remodeling in isolated subendocardial resistance vessels.
The capacity for myocardial perfusion depends on the structure of the coronary microvascular bed. Coronary microvessels may adapt their structure to various stimuli. We tested whether the local pressure profile affects tone and remodeling of porcine coronary microvessels. Subendocardial vessels (approximately 160 microm, n=53) were cannulated and kept in organoid culture for 3 days under different transvascular pressure profiles: Osc 80: mean 80 mmHg, 60 mmHg peak-peak sine wave pulsation amplitude at 1.5 Hz; St 80: steady 80 mmHg; Osc 40: mean 40 mmHg, 30 mmHg amplitude; St 40: steady 40 mmHg. Under the Osc 80 profile, modest tone developed, reducing the diameter to 81+/-14% (mean+/-SE, 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., Osc 40: 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., Osc 40: passive diameter reduction by 24+/-3%). The calcium blocker amlodipine induced maintained dilation in St 40 vessels and reversed the 22+/-3% (n=6) inward remodeling to 15+/-3% (n=8) outward remodeling toward day 3. Vessels required a functional endothelium 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. Although microvascular pressure profiles distal to stenoses are poorly defined, these data suggest that vasodilator therapy could improve subendocardial microvascular function and structure in coronary artery disease.
Department of Medical Physics, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
Oana
O
Sorop
Erik N T P
EN
Bakker
Adrian
A
Pistea
Jos A E
JA
Spaan
Ed
E
VanBavel
D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000503:physiopathology; D023921:Coronary Stenosis / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004699:Endocardium / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009569:Nitric Oxide