3.4 Effects of the BK-(1-9) fragments on vascular tissue ex vivo
BK-(1-9) is known to induce vasodilation due to NO and prostacyclin
production in endothelial cells (Marceau et al. , 2020). Given the
fact that BK-(1-7) and BK-(1-5) were able to induce NO production in
vitro, it was highly likely that these fragments could also promote
vasodilation. In aortic rings from male rats, BK-(1-9) induced a
concentration-dependent vasorelaxation at lower concentrations and
vasoconstriction at higher concentrations (Figure 5A). BK-(1-7) (Figure
5B) and BK-(1-5) (Figure 5C) induced a concentration-dependent
vasorelaxation only. The maximum vasorelaxation (Emax),
expressed as a percentage in relation to the vasoconstriction induced by
phenylephrine, was 15 ± 2% for BK-(1-9),
19 ± 2% for BK-(1-7) and 18 ± 2%
for BK-(1-5).
Furthermore, the vascular effect of BK-(1-9) was completely blocked when
the endothelial cells were mechanically removed (Figure 5D) or when NOS
was pharmacologically blocked by L-NAME (Figure 5G), whereas
BK-(1-9)-induced vasorelaxation was only partly blocked by
pharmacological inhibition of cyclooxygenases by indomethacin (Figure
5J). BK-(1-7)-induced vasodilation was partly dependent on endothelial
integrity (Figure 5E) and prostanoid production (Figure 5K), while NO
production was essential for the BK-(1-7)-induced vasorelaxation (Figure
5H). BK-(1-5) vasoactivity relied on functional endothelium (Figure 5F),
and production of both NO (Figure 5I) and prostanoids (Figure 5L). These
results suggest that these three peptides, BK-(1-9), BK-(1-7) and
BK-(1-5), induced vasorelaxation by different mechanisms.