Figure legends
Figure 1. Mean lumen diameter (A), contractile response to 32 mM
K+ (B), relaxing response to 1 μM bradykinin (C) and
the relation of the K+-induced contraction to the
lumen diameter (D) in the pericardial resistance arteries investigated.
Data are shown as mean of the observations in 3 – 6 arterial segments
from the same patient (dots) and as median and interquartile range of
the entire study group.
Figure 2. Relaxing responses to bradykinin (BK) during contraction
stimulated by K+ or endothelin-1 (ET-1) in
preparations without (+Endo) and with (-Endo) prior gentle mechanical
damage of their luminal surface. Mean observations (A) along with
typical tracings of tension as a function of time illustrating effects
of BK during contraction stimulated with K+ (B) or
ET-1 (C) in arterial segments from the same patient.
Figure 3. Immunohistochemical (IHC) staining for detection of
NO-synthases and antioxidant enzymes in patient pericardial resistance
arteries illustrated by typical examples and results of
semi-quantitative analyses summarized by violin plots (N = 28). A and B,
endothelial NO-synthase (eNOS) in a pericardial resistance artery and an
atrial appendage, respectively. C, inducible NO-synthase (iNOS), D,
neuronal NO-synthase (nNOS), E, catalase (CAT) and F, superoxide
dismutase 1 (SOD1) in pericardial resistance arteries. EC, endothelium;
SMC, medial smooth muscle; ADV, tunica adventitia. Scale bar 50 μm.
Figure 4. Effects of inhibition of
prostanoid, oxidative and nitrosative processes on
endothelium-independent SNP-induced relaxations in
K+-precontracted pericardial arteries. A and B,
relaxing responses to 1 µM SNP in the absence and presence of 100 µM
L-NAME, 300 µM c-PTIO and 10 µM ODQ in the absence (A) and presence of
10 µM indomethacin (INDO, B). C and D, cumulative-concentration response
curves to SNP (C) and CXL-1020 (D) in the absence and presence of 3 mM
NAC, 3 mM DETCA and 50 mM Amitrole. Data are shown as means ± SEM; n =
6-12. *, significantly different from control after comparison by
one-way mixed-effects ANOVA corrected for multiple comparisons by
Dunett’s post-hoc test.
Figure 5. Effects of 2000 U/ml catalase (CAT) and 100 µM L-NAME on
relaxing responses to H2O2 in
pericardial arteries made to contract with 32 mM K+(A) or an equieffective concentration of ET-1 (B). Data are shown as
means ± SEM; n = 5-9. *, significantly different from control
after comparison by one-way
mixed-effects ANOVA corrected for multiple comparisons by Dunett’s
post-hoc test.
Figure 6. Effects of inhibition and scavenging of cyclooxygenase,
nitrosative and oxidative pathways on contractile responses to 32 mM
K+ in pericardial resistance arteries. A, effect of
300 µM c-PTIO, 100 µM L-NAME and 10 µM ODQ in the absence (circles) and
presence (rhombuses) of 10 µM indomethacin (INDO). B, effect of 3 mM
NAC, 3 mM DETCA and 50 mM amitrole; C, 2000 U/ml CAT, 2000 U/ml CAT +
100 µM L-NAME and 100 µM L-NAME; and D, 100 µM 7-NI, 3 µM NPLA and 100
µM L-NAME on the contractile response in segments from the same
arteries, respectively. Data are shown as mean ± SEM; N = 6-15.* , P < 0.05 significantly different from
control; #, P < 0.05 compared to Control + INDO.
Statistical significance of differences was assessed by one-way
mixed-effects ANOVA corrected for multiple comparisons by Dunett’s
post-hoc test.
Figure 7. Effects of inhibition of cyclooxygenase, nitrosative and
oxidative processes on BK-induced relaxations in pericardial resistance
arteries precontracted with 32 mM K+. A and B,
relaxing responses to 1 µM BK in the absence and presence of 100 µM
L-NAME, 300 µM c-PTIO and 10 µM ODQ in the absence (A, circles) and
presence of 10 µM indomethacin (INDO) (B, rhombuses). C and D,
cumulative-concentration response curves to BK in the absence and
presence of 3 mM NAC, 3 mM DETCA and 50 mM Amitrole (C) or 2000 U/ml
CAT, 2000 U/ml CAT + 100 µM L-NAME and L-NAME alone. Data are shown as
means ± SEM; N = 6-14. * , P < 0.05 versus
control (one-way mixed-effects ANOVA corrected for multiple comparisons
by Dunett’s post-hoc test).
Figure 8. Effects of non-selective NOS inhibition and nNOS-selective
inhibition on BK-induced endothelium-dependent relaxation in pericardial
resistance arteries. Cumulative concentration response curves
summarizing relaxing effects of BK in K+- (A) and
ET-1- (B) pre-contracted arteries in the absence and presence of 100 µM
7-NI, 3 µM NPLA or 100 µM L-NAME. Data are shown as means ± SEM; n =
5-11. *, P < 0.05 versus control (one-way mixed-effects ANOVA
corrected for multiple comparisons by Dunett’s post-hoc test).
Figure 9. Effects of inhibition of cyclooxygenase, nitrosative and
oxidative processes on BK-induced relaxations in pericardial resistance
arteries precontracted with ET-1. A and B, relaxing responses to 1
µM BK in the absence and presence
of 100 µM L-NAME, 300 µM c-PTIO and 10 µM ODQ in the absence (A,
circles) and presence of 10 µM indomethacin (INDO) (B, rhombuses). C and
D, cumulative-concentration response curves to BK in the absence and
presence of 3 mM NAC, 3 mM DETCA and 50 mM Amitrole (C) or 2000 U/ml
CAT, 2000 U/ml CAT + 100 µM L-NAME and L-NAME alone. Data are shown as
means ± SEM; N = 6-12. * , P < 0.05 versus
control (one-way mixed-effects ANOVA corrected for multiple comparisons
by Dunett’s post-hoc test). These results were obtained after the same
arterial segments were investigated for BK-induced relaxation during
K+-induced contraction (Figure 7).
Figure 10. Comparison between arteries from patients that required
coronary bypass grafting (CABG, left) or valve replacement surgery (VRS,
right). The individual data illustrate the effect of 100 µM L-NAME on
the relaxing response to 1 µM BK in the same arterial segments made to
contract with 32 mM K+ or ET-1.
Figure 1
Figure 2
Figure 3