Limits...
Suppression of peripheral sympathetic activity underlies protease-activated receptor 2-mediated hypotension.

Kim YH, Ahn DS, Joeng JH, Chung S - Korean J. Physiol. Pharmacol. (2014)

Bottom Line: In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA).Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx.These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.

ABSTRACT
Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ω-conotoxin GVIA (CgTx), a selective N-type Ca(2+) channel (ICa-N) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

No MeSH data available.


Related in: MedlinePlus

Effect of NA and of NA plus PAR-2 agonists on the response to EFS-induced contraction in endothelium-denuded superior mesenteric arterial strip. (A) A representative trace of trypsin (30 nM) effect on the contraction evoked by externally applied NA (1µM). (B) Summary of trypsin effect on NA-evoked vasoconstriction (0.55±0.13 g for NA, 0.53±0.13 g for NA+trypsin, n=5, p>0.05). (C) A representative trace of SL-NH2 (100µM) effect on the contraction evoked by externally applied NA (1µM). (D) Summary of SL-NH2 effect on NA-evoked vasoconstriction (0.7±0.05 g for NA; 0.66±0.03 g for NA+SL-NH2, n=5, p>0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4296038&req=5

Figure 2: Effect of NA and of NA plus PAR-2 agonists on the response to EFS-induced contraction in endothelium-denuded superior mesenteric arterial strip. (A) A representative trace of trypsin (30 nM) effect on the contraction evoked by externally applied NA (1µM). (B) Summary of trypsin effect on NA-evoked vasoconstriction (0.55±0.13 g for NA, 0.53±0.13 g for NA+trypsin, n=5, p>0.05). (C) A representative trace of SL-NH2 (100µM) effect on the contraction evoked by externally applied NA (1µM). (D) Summary of SL-NH2 effect on NA-evoked vasoconstriction (0.7±0.05 g for NA; 0.66±0.03 g for NA+SL-NH2, n=5, p>0.05).

Mentions: To exclude the possibility that the inhibition of EFS-contraction by PAR-2 agonists was mediated by direct inhibition of vascular smooth muscle contraction, we investigated the effects of PAR-2 agonists on contraction evoked by externally applied NA in endothelium-denuded superior mesenteric arterial strips. As shown in Fig. 2, externally applied NA (1µM) evoked contractions of endothelium-denuded superior mesenteric arterial strips. Trypsin (30 nM) failed to affect the contraction evoked by externally applied NA (Fig. 2A, B). Likewise, SL-NH2 (100µM) had no effect on the NA-induced contraction (Fig. 2C, D). For comparison, we investigated the effects of thrombin, a potent PAR-1 agonist on EFS-induced contraction. Thrombin (30 nM), did not show any effects on EFS-evoked contraction in endothelium-denuded superior mesenteric arterial strips (Supplmental Fig. 2). These results suggest that EFS-evoked contraction is suppressed not by PAR-1, but by PAR-2 activation and that the suppression by PAR-2 activation, may be mediated by inhibiting the peripheral sympathetic neuronal output that regulates peripheral vascular sympathetic tone. These results suggest that EFS-evoked contraction is suppressed by PAR-2 activation and that the suppression by PAR-2 activation may be mediated by inhibiting the peripheral sympathetic neuronal output that regulates peripheral vascular sympathetic tone.


Suppression of peripheral sympathetic activity underlies protease-activated receptor 2-mediated hypotension.

Kim YH, Ahn DS, Joeng JH, Chung S - Korean J. Physiol. Pharmacol. (2014)

Effect of NA and of NA plus PAR-2 agonists on the response to EFS-induced contraction in endothelium-denuded superior mesenteric arterial strip. (A) A representative trace of trypsin (30 nM) effect on the contraction evoked by externally applied NA (1µM). (B) Summary of trypsin effect on NA-evoked vasoconstriction (0.55±0.13 g for NA, 0.53±0.13 g for NA+trypsin, n=5, p>0.05). (C) A representative trace of SL-NH2 (100µM) effect on the contraction evoked by externally applied NA (1µM). (D) Summary of SL-NH2 effect on NA-evoked vasoconstriction (0.7±0.05 g for NA; 0.66±0.03 g for NA+SL-NH2, n=5, p>0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296038&req=5

Figure 2: Effect of NA and of NA plus PAR-2 agonists on the response to EFS-induced contraction in endothelium-denuded superior mesenteric arterial strip. (A) A representative trace of trypsin (30 nM) effect on the contraction evoked by externally applied NA (1µM). (B) Summary of trypsin effect on NA-evoked vasoconstriction (0.55±0.13 g for NA, 0.53±0.13 g for NA+trypsin, n=5, p>0.05). (C) A representative trace of SL-NH2 (100µM) effect on the contraction evoked by externally applied NA (1µM). (D) Summary of SL-NH2 effect on NA-evoked vasoconstriction (0.7±0.05 g for NA; 0.66±0.03 g for NA+SL-NH2, n=5, p>0.05).
Mentions: To exclude the possibility that the inhibition of EFS-contraction by PAR-2 agonists was mediated by direct inhibition of vascular smooth muscle contraction, we investigated the effects of PAR-2 agonists on contraction evoked by externally applied NA in endothelium-denuded superior mesenteric arterial strips. As shown in Fig. 2, externally applied NA (1µM) evoked contractions of endothelium-denuded superior mesenteric arterial strips. Trypsin (30 nM) failed to affect the contraction evoked by externally applied NA (Fig. 2A, B). Likewise, SL-NH2 (100µM) had no effect on the NA-induced contraction (Fig. 2C, D). For comparison, we investigated the effects of thrombin, a potent PAR-1 agonist on EFS-induced contraction. Thrombin (30 nM), did not show any effects on EFS-evoked contraction in endothelium-denuded superior mesenteric arterial strips (Supplmental Fig. 2). These results suggest that EFS-evoked contraction is suppressed not by PAR-1, but by PAR-2 activation and that the suppression by PAR-2 activation, may be mediated by inhibiting the peripheral sympathetic neuronal output that regulates peripheral vascular sympathetic tone. These results suggest that EFS-evoked contraction is suppressed by PAR-2 activation and that the suppression by PAR-2 activation may be mediated by inhibiting the peripheral sympathetic neuronal output that regulates peripheral vascular sympathetic tone.

Bottom Line: In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA).Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx.These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.

ABSTRACT
Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ω-conotoxin GVIA (CgTx), a selective N-type Ca(2+) channel (ICa-N) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

No MeSH data available.


Related in: MedlinePlus