3.4 Relaxing responses to exogenous NO, HNO and
H2O2
One μM Na-nitroprusside (SNP, NO-donor), reduced contractile responses
to 32 mM K+ (-58
± 6%, N = 9; Figure 4A). L-NAME tended to increase this relaxing effect
(-74 ± 5%, N = 9) but this did not reach statistical significance
(P = 0.054). c-PTIO and ODQ abolished relaxing responses to 1 μM
SNP (Figure 4A). Indomethacin did not modify the relaxing effect of SNP
and its inhibition by c-PTIO and ODQ (Figure 4B). Relaxing responses to
0.001 – 1 μM SNP during K+-induced contraction were
not modified by NAC which scavenges HNO but not NO (Figure 4C). DETCA
had a profound inhibitory effect on relaxing responses to SNP while
amitrole slightly increased its efficacy (Figure 4C).
CXL-1020 was less potent than SNP but at least as efficacious in
relaxing depolarized human pericardial resistance arteries (Figure 4D).
The potency of this HNO-donor compound was significantly reduced in the
presence of NAC which did not reduce relaxing responses to SNP. DETCA
and amitrole, on the other hand, did not modify the relaxing effects of
CXL-1020 (Figure 4D).
During contraction stimulated with 32 mM K+, exogenous
H2O2caused relaxations with smaller potency but similar efficacy, compared
to SNP and CXL-1020 (Figure 5A). H2O2was approximately 10 times more potent in reducing contractions induced
by ET-1 (Figure 5B). Irrespective of the type of contractile stimulus,
relaxing effects of H2O2 were not
significantly modified by L-NAME but, even at high concentrations,
abolished in the presence of exogenous catalase (Figure 5).