A new experimental approach in endothelium-dependent pharmacological investigations on isolated porcine coronary arteries mounted for impedance planimetry.
1. The aim of this study was to investigate whether the balloon-based impedance planimetry technique could be a useful tool in endothelium-dependent investigations. 2. Porcine large coronary arteries contracted with prostaglandin F2alpha (PGF2alpha, 10 microM) did not relax to bradykinin (0.1 nM - 0.1 microM), but did relax to sodium nitroprusside (SNP, 10 microM). However, after eversion of the segments, bradykinin induced relaxations with pD2 values and maximal responses of 8.78+/-0.09 and 75+/-2% (n=6), respectively. 3. Incubation with captopril (1 microM) did not reveal a relaxation to bradykinin in the normal vessel configuration and had no influence on the concentration-relaxation relationship in everted segments. 4. Lowering the luminal pressure in contracted segments from 131+/-5 mmHg (isometric, n=5) to 60 mmHg (isobaric, n=5) did not facilitate the action of bradykinin. 5. Eversion of segments did not influence the concentration-response relationship for K+ (4.7 - 125 mM), PGF2alpha (0.3 - 30 microM), and SNP (30 nM - 30 microM), although the time-courses of responses were faster when the agents were added from the intimal compared to the adventitial side of the preparation. 6. In the same everted segment contracted with PGF2alpha, the concentration-response relationship for bradykinin was not different under isometric and isobaric conditions. 7. These results indicate that, (1) reduced endothelium-dependent relaxations to adventitially administered substances can be ascribed to a diffusion barrier in the vessel wall, while enzymatic degradation, luminal pressure and precontractile responses seem not to play a role, (2) impedance planimetry applied to everted cylindrical segments could be a useful experimental approach in pharmacological studies of endothelium-dependent responses under isobaric and isometric conditions.
Tankó
L B
LB
Department of Pharmacology, University of Aarhus, The Bartholin Building, DK-8000 Aarhus C, Denmark. ltanko@farm.aau.dk
Mikkelsen
E O
EO
Simonsen
U
U
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D004058:Diffusion; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011312:Pressure; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D009599:Nitroprusside; D013373:Substance P; D000001:Calcimycin; D002216:Captopril; D015237:Dinoprost; D007703:Peptidyl-Dipeptidase A; D011188:Potassium; D001920:Bradykinin