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.