Article date: October 1995
By: Mari Kuroiwa, Hiroki Aoki, Sei Kobayashi, Junji Nishimura, Hideo Kanaide, in Volume 116, Issue 3, pages 2040-2047
Using front‐surface fluorometry of fura‐2‐loaded porcine coronary arterial strips with the endothelium intact, we investigated the mechanisms of vasorelaxation induced by substance P (SP). Fura‐2 fluorescence signals which indicated the cytosolic Ca2+‐concentration ([Ca2+]i), were observed to arise exclusively from the smooth muscle cells in these strips.
During the contractions induced by U46619 (100 nM), a thromboxane A2 analogue, an SP‐induced endothelium‐dependent, biphasic vasorelaxation was observed, which consisted of an initial rapid relaxation phase followed by a sustained phase, with a transient decrease in [Ca2+]i. Pretreatment with indomethacin (Ind) had no effect on the SP‐induced relaxation; however, pretreatment with NG‐nitro‐L‐arginine (l‐NOARG) partially, but significantly inhibited the decrease in both the [Ca2+]i and tension induced by SP; in addition, the sustained phase of SP‐induced relaxation was almost completely abolished. Thus, part of the relaxation was considered to be mediated by L‐NOARG‐sensitive relaxing factor (endothelium‐derived relaxing factor: EDRF).
During the 40 mM K+‐depolarization‐induced contraction which may eliminate the effects of endothelium‐derived hyperpolarizing factor (EDHF), the vasorelaxation induced by SP was completely inhibited by L‐NOARG.
During the vasorelaxation induced by SP, the [Ca2+]itension relationships shifted to the right of the contractions induced by either U46619 or high K+‐depolarization.
Using front‐surface fluorometry of fura‐2 loaded porcine aortic valvular strips, we examined the effects of SP on [Ca2+]i in endothelial cells in situ. SP induced a rapid increase in [Ca2+]i of endothelial cells in situ followed by a small sustained phase in normal PSS (5.9 mM K+). The increase in extracellular K+ had no apparent effect on the SP‐induced [Ca2+]i elevation of endothelial cells.
We thus conclude that: (1) SP‐induced vasorelaxation is mediated by an L‐NOARG‐sensitive factor (EDRF) and an L‐NOARG‐resistant factor; and (2) the first, rapid, phase of the relaxation is mediated by both factors while the sustained phase seems to be mediated mainly by EDRF. The underlying mechanisms of L‐NOARG‐resistant relaxation have yet to be elucidated, but EDHF appears to be a potentially contributing factor.
Using front‐surface fluorometry of fura‐2‐loaded porcine coronary arterial strips with the endothelium intact, we investigated the mechanisms of vasorelaxation induced by substance P (SP). Fura‐2 fluorescence signals which indicated the cytosolic Ca2+‐concentration ([Ca2+]i), were observed to arise exclusively from the smooth muscle cells in these strips.
During the contractions induced by U46619 (100 nM), a thromboxane A2 analogue, an SP‐induced endothelium‐dependent, biphasic vasorelaxation was observed, which consisted of an initial rapid relaxation phase followed by a sustained phase, with a transient decrease in [Ca2+]i. Pretreatment with indomethacin (Ind) had no effect on the SP‐induced relaxation; however, pretreatment with NG‐nitro‐L‐arginine (l‐NOARG) partially, but significantly inhibited the decrease in both the [Ca2+]i and tension induced by SP; in addition, the sustained phase of SP‐induced relaxation was almost completely abolished. Thus, part of the relaxation was considered to be mediated by L‐NOARG‐sensitive relaxing factor (endothelium‐derived relaxing factor: EDRF).
During the 40 mM K+‐depolarization‐induced contraction which may eliminate the effects of endothelium‐derived hyperpolarizing factor (EDHF), the vasorelaxation induced by SP was completely inhibited by L‐NOARG.
During the vasorelaxation induced by SP, the [Ca2+]itension relationships shifted to the right of the contractions induced by either U46619 or high K+‐depolarization.
Using front‐surface fluorometry of fura‐2 loaded porcine aortic valvular strips, we examined the effects of SP on [Ca2+]i in endothelial cells in situ. SP induced a rapid increase in [Ca2+]i of endothelial cells in situ followed by a small sustained phase in normal PSS (5.9 mM K+). The increase in extracellular K+ had no apparent effect on the SP‐induced [Ca2+]i elevation of endothelial cells.
We thus conclude that: (1) SP‐induced vasorelaxation is mediated by an L‐NOARG‐sensitive factor (EDRF) and an L‐NOARG‐resistant factor; and (2) the first, rapid, phase of the relaxation is mediated by both factors while the sustained phase seems to be mediated mainly by EDRF. The underlying mechanisms of L‐NOARG‐resistant relaxation have yet to be elucidated, but EDHF appears to be a potentially contributing factor.
DOI: 10.1111/j.1476-5381.1995.tb16409.x
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