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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 PAR-2 agonist on EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips. (A) summary of the effects of trypsin (7.1±0.2 pq/ml for control, 6.0±0.3 pq/ml for trypsin, n=4, p<0.001), SL-NH2 (7.0±0.3 pq/ml for control; 6.1±0.2 pq/ml for SL-NH2, n=4, p<0.001), BT (6.2±0.2 pq/ml for control, 6.3±0.2 pq/ml for BT, n=4, P>0.05), or LR-NH2 (6.7±0.2 pq/ml for control; 6.8±0.2 pq/ml for LR-NH2, n=4, p>0.05) on the EFS-evoked overflow of NA in rat superior mesenteric arterial strips. (B) summary of ω-CgTx effect on trypsin or SL-NH2-induced inhibition of EFS-evoked overflow of NA in rat superior mesenteric arterial strips (ω-CgTx; 17.6±0.5%, ω-CgTx+trypsin; 17.7±1.1%, p>0.05, n=4), (ω-CgTx; 16.1±0.6%, ω-CgTx+SL-NH2; 15.8±1.2%, p>0.05, n=4).
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Figure 4: Effect of PAR-2 agonist on EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips. (A) summary of the effects of trypsin (7.1±0.2 pq/ml for control, 6.0±0.3 pq/ml for trypsin, n=4, p<0.001), SL-NH2 (7.0±0.3 pq/ml for control; 6.1±0.2 pq/ml for SL-NH2, n=4, p<0.001), BT (6.2±0.2 pq/ml for control, 6.3±0.2 pq/ml for BT, n=4, P>0.05), or LR-NH2 (6.7±0.2 pq/ml for control; 6.8±0.2 pq/ml for LR-NH2, n=4, p>0.05) on the EFS-evoked overflow of NA in rat superior mesenteric arterial strips. (B) summary of ω-CgTx effect on trypsin or SL-NH2-induced inhibition of EFS-evoked overflow of NA in rat superior mesenteric arterial strips (ω-CgTx; 17.6±0.5%, ω-CgTx+trypsin; 17.7±1.1%, p>0.05, n=4), (ω-CgTx; 16.1±0.6%, ω-CgTx+SL-NH2; 15.8±1.2%, p>0.05, n=4).

Mentions: We examined the effects of PAR-2 agonists on the EFS-evoked overflow of NA in superior mesenteric arterial strips. As shown in Fig. 4A, 30 nM trypsin reduced the EFS-evoked overflow of NA by 14.9±1.9%. However, 30 nM boiled trypsin (BT) did not have any effect on the EFS-evoked overflow of NA in superior mesenteric arterial strips (Fig. 4A). Likewise, 100 µM SL-NH2 decreased the EFS-evoked overflow of NA by 13.2±1.2% (Fig. 4A). On the contrary, 100µM LR-NH2, a control reverse peptide, had no influence on the EFS-evoked overflow of NA in superior mesenteric arterial strips (Fig. 4A).


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 PAR-2 agonist on EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips. (A) summary of the effects of trypsin (7.1±0.2 pq/ml for control, 6.0±0.3 pq/ml for trypsin, n=4, p<0.001), SL-NH2 (7.0±0.3 pq/ml for control; 6.1±0.2 pq/ml for SL-NH2, n=4, p<0.001), BT (6.2±0.2 pq/ml for control, 6.3±0.2 pq/ml for BT, n=4, P>0.05), or LR-NH2 (6.7±0.2 pq/ml for control; 6.8±0.2 pq/ml for LR-NH2, n=4, p>0.05) on the EFS-evoked overflow of NA in rat superior mesenteric arterial strips. (B) summary of ω-CgTx effect on trypsin or SL-NH2-induced inhibition of EFS-evoked overflow of NA in rat superior mesenteric arterial strips (ω-CgTx; 17.6±0.5%, ω-CgTx+trypsin; 17.7±1.1%, p>0.05, n=4), (ω-CgTx; 16.1±0.6%, ω-CgTx+SL-NH2; 15.8±1.2%, p>0.05, n=4).
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Figure 4: Effect of PAR-2 agonist on EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips. (A) summary of the effects of trypsin (7.1±0.2 pq/ml for control, 6.0±0.3 pq/ml for trypsin, n=4, p<0.001), SL-NH2 (7.0±0.3 pq/ml for control; 6.1±0.2 pq/ml for SL-NH2, n=4, p<0.001), BT (6.2±0.2 pq/ml for control, 6.3±0.2 pq/ml for BT, n=4, P>0.05), or LR-NH2 (6.7±0.2 pq/ml for control; 6.8±0.2 pq/ml for LR-NH2, n=4, p>0.05) on the EFS-evoked overflow of NA in rat superior mesenteric arterial strips. (B) summary of ω-CgTx effect on trypsin or SL-NH2-induced inhibition of EFS-evoked overflow of NA in rat superior mesenteric arterial strips (ω-CgTx; 17.6±0.5%, ω-CgTx+trypsin; 17.7±1.1%, p>0.05, n=4), (ω-CgTx; 16.1±0.6%, ω-CgTx+SL-NH2; 15.8±1.2%, p>0.05, n=4).
Mentions: We examined the effects of PAR-2 agonists on the EFS-evoked overflow of NA in superior mesenteric arterial strips. As shown in Fig. 4A, 30 nM trypsin reduced the EFS-evoked overflow of NA by 14.9±1.9%. However, 30 nM boiled trypsin (BT) did not have any effect on the EFS-evoked overflow of NA in superior mesenteric arterial strips (Fig. 4A). Likewise, 100 µM SL-NH2 decreased the EFS-evoked overflow of NA by 13.2±1.2% (Fig. 4A). On the contrary, 100µM LR-NH2, a control reverse peptide, had no influence on the EFS-evoked overflow of NA in superior mesenteric arterial strips (Fig. 4A).

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