A new experimental approach in endothelium-dependent pharmacological investigations on isolated porcine coronary arteries mounted for impedance planimetry
Ib. Tanko et al., A new experimental approach in endothelium-dependent pharmacological investigations on isolated porcine coronary arteries mounted for impedance planimetry, BR J PHARM, 128(1), 1999, pp. 165-173
1 The aim of this study was to investigate whether the balloon-based impeda
nce planimetry technique could be a useful tool in endothelium-dependent in
vestigations.
2 Porcine large coronary arteries contracted with prostaglandin F-2 alpha (
PGF(2 alpha), 10 mu M) did not relax to bradykinin (0.1 nM-0.1 mu M), but d
id relax to sodium nitroprusside (SNP, 10 mu M). However, after eversion of
the segments, bradykinin induced relaxations with pD(2) values and maximal
responses of 8.78 +/- 0.09 and 75 +/- 2% (n = 6), respectively.
3 Incubation with captopril (1 mu M) did not reveal a relaxation to bradyki
nin in the normal vessel configuration and had no influence on the concentr
ation-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 acti
on of bradykinin.
5 Eversion of segments did not influence the concentration-response relatio
nship for K+ (4.7-125 mM), PGF(2 alpha) (0.3-30 mu M), and SNP (30 nM-30 mu
M), although the time-courses of responses were faster when the agents wer
e added from the intimal compared to the adventitial side of the preparatio
n.
6 In the same everted segment contracted with PGF(2 alpha), the concentrati
on-response relationship for bradykinin was not different under isometric a
nd isobaric conditions.
7 These results indicate that, (1) reduced endothelium-dependent relaxation
s to adventitially administered substances can be ascribed to a diffusion b
arrier in the vessel wall, while enzymatic degradation, luminal pressure an
d precontractile responses seem not to play a role, (2) impedance planimetr
y applied to everted cylindrical segments could be a useful experimental ap
proach in pharmacological studies of endothelium-dependent responses under
isobaric and isometric conditions.