The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

Suppression of Peripheral Sympathetic Activity Underlies Protease-Activated Receptor 2-Mediated Hypotension

  • Kim, Young-Hwan (Department of Physiology, Yonsei University College of Medicine) ;
  • Ahn, Duck-Sun (Department of Physiology, Yonsei University College of Medicine) ;
  • Joeng, Ji-Hyun (Department of Physiology, Yonsei University College of Medicine) ;
  • Chung, Seungsoo (Department of Physiology, Yonsei University College of Medicine)
  • Received : 2014.06.25
  • Accepted : 2014.09.23
  • Published : 2014.12.30
Download PDF
⟨ Previous Next ⟩

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, ${\omega}$-conotoxin GVIA (CgTx), a selective N-type $Ca^{2+}$ channel ($I_{Ca-N}$) 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 ${\omega}$-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of $I_{Ca-N}$ which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

Keywords

References

  1. Kawabata A, Kuroda R, Hollenberg MD. Physiology of protease-activated receptors (PARs): involvement of PARs in digestive functions. Nihon Yakurigaku Zasshi. 1999;114 Suppl 1:173-179P. https://doi.org/10.1254/fpj.114.supplement_173
  2. al-Ani B, Saifeddine M, Hollenberg MD. Detection of functional receptors for the proteinase-activated-receptor-2-activating polypeptide, SLIGRL-NH2, in rat vascular and gastric smooth muscle. Can J Physiol Pharmacol. 1995;73:1203-1207. https://doi.org/10.1139/y95-172
  3. Hollenberg MD, Saifeddine M, al-Ani B. Proteinase-activated receptor-2 in rat aorta: structural requirements for agonist activity of receptor-activating peptides. Mol Pharmacol. 1996; 49:229-233.
  4. Magazine HI, King JM, Srivastava KD. Protease activated receptors modulate aortic vascular tone. Int J Cardiol. 1996;53 Suppl:S75-80. https://doi.org/10.1016/0167-5273(96)02569-7
  5. Saifeddine M, al-Ani B, Cheng CH, Wang L, Hollenberg MD. Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue. Br J Pharmacol. 1996;118:521-530. https://doi.org/10.1111/j.1476-5381.1996.tb15433.x
  6. Emilsson K, Wahlestedt C, Sun MK, Nystedt S, Owman C, Sundelin J. Vascular effects of proteinase-activated receptor 2 agonist peptide. J Vasc Res. 1997;34:267-272. https://doi.org/10.1159/000159233
  7. Cicala C, Pinto A, Bucci M, Sorrentino R, Walker B, Harriot P, Cruchley A, Kapas S, Howells GL, Cirino G. Proteaseactivated receptor-2 involvement in hypotension in normal and endotoxemic rats in vivo. Circulation. 1999;99:2590-2597. https://doi.org/10.1161/01.CIR.99.19.2590
  8. Cicala C, Morello S, Santagada V, Caliendo G, Sorrentino L, Cirino G. Pharmacological dissection of vascular effects caused by activation of protease-activated receptors 1 and 2 in anesthetized rats. FASEB J. 2001;15:1433-1435. https://doi.org/10.1096/fj.00-0633fje
  9. Cheung WM, Andrade-Gordon P, Derian CK, Damiano BP. Receptor-activating peptides distinguish thrombin receptor (PAR-1) and protease activated receptor 2 (PAR-2) mediated hemodynamic responses in vivo. Can J Physiol Pharmacol. 1998;76:16-25. https://doi.org/10.1139/y97-176
  10. Damiano BP, Cheung WM, Santulli RJ, Fung-Leung WP, Ngo K, Ye RD, Darrow AL, Derian CK, de Garavilla L, Andrade- Gordon P. Cardiovascular responses mediated by proteaseactivated receptor-2 (PAR-2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR-2 or PAR-1. J Pharmacol Exp Ther. 1999;288:671-678.
  11. Kawabata A, Nakaya Y, Kuroda R, Wakisaka M, Masuko T, Nishikawa H, Kawai K. Involvement of EDHF in the hypotension and increased gastric mucosal blood flow caused by PAR-2 activation in rats. Br J Pharmacol. 2003;140:247-254. https://doi.org/10.1038/sj.bjp.0705433
  12. Lee CC, Lee YY, Chang CK, Lin MT. Selective inhibition of inducible nitric oxide synthase attenuates renal ischemia and damage in experimental heatstroke. J Pharmacol Sci. 2005; 99:68-76. https://doi.org/10.1254/jphs.FP0050300
  13. Emilsson V, Arch JR, de Groot RP, Lister CA, Cawthorne MA. Leptin treatment increases suppressors of cytokine signaling in central and peripheral tissues. FEBS Lett. 1999;455:170-174. https://doi.org/10.1016/S0014-5793(99)00874-1
  14. Molderings GJ, Likungu J, Gothert M. N-Type calcium channels control sympathetic neurotransmission in human heart atrium. Circulation. 2000;101:403-407. https://doi.org/10.1161/01.CIR.101.4.403
  15. Shimosawa T, Takano K, Ando K, Fujita T. Magnesium inhibits norepinephrine release by blocking N-type calcium channels at peripheral sympathetic nerve endings. Hypertension. 2004;44: 897-902. https://doi.org/10.1161/01.HYP.0000146536.68208.84
  16. Ryu SK, Ahn DS, Cho YE, Choi SK, Kim YH, Morgan KG, Lee YH. Augmented sphingosylphosphorylcholine-induced $Ca^{2+}$- sensitization of mesenteric artery contraction in spontaneously hypertensive rat. Naunyn Schmiedebergs Arch Pharmacol. 2006;373:30-36. https://doi.org/10.1007/s00210-006-0036-7
  17. Zygmunt PM, Hogestatt ED. Calcium channels at the adrenergic neuroeffector junction in the rabbit ear artery. Naunyn Schmiedebergs Arch Pharmacol. 1993;347:617-623. https://doi.org/10.1007/BF00166944
  18. Ralevic V, Karoon P, Burnstock G. Long-term sensory denervation by neonatal capsaicin treatment augments sympathetic neurotransmission in rat mesenteric arteries by increasing levels of norepinephrine and selectively enhancing postjunctional actions. J Pharmacol Exp Ther. 1995;274:64-71.
  19. Kim T, La J, Lee J, Yang I. Effects of nitric oxide on slow waves and spontaneous contraction of guinea pig gastric antral circular muscle. J Pharmacol Sci. 2003;92:337-347. https://doi.org/10.1254/jphs.92.337
  20. Asano M, Nomura N, Sasaki S, Mishima A. Surgical repair of tetralogy of Fallot with large conus artery. Pediatr Cardiol. 2003;24:601-603. https://doi.org/10.1007/s00246-002-0388-9
  21. Nystedt S, Emilsson K, Wahlestedt C, Sundelin J. Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci U S A. 1994;91:9208-9212. https://doi.org/10.1073/pnas.91.20.9208
  22. Lamont C, Vainorius E, Wier WG. Purinergic and adrenergic $Ca^{2+}$ transients during neurogenic contractions of rat mesenteric small arteries. J Physiol. 2003;549:801-808. https://doi.org/10.1113/jphysiol.2003.043380
  23. Sadraei H, Large BJ, Hughes IE. Mechanisms involved in electrically-induced responses of rat seminal vesicles. J Pharm Pharmacol. 1995;47:665-668. https://doi.org/10.1111/j.2042-7158.1995.tb05856.x
  24. Tanaka Y, Mochizuki Y, Tanaka H, Shigenobu K. Significant role of neuronal non-N-type calcium channels in the sympathetic neurogenic contraction of rat mesenteric artery. Br J Pharmacol. 1999;128:1602-1608. https://doi.org/10.1038/sj.bjp.0702954
  25. Recio P, Orensanz LM, Martinez MP, Navarro-Dorado J, Bustamante S, Garcia-Sacristan A, Prieto D, Hernández M. Noradrenergic vasoconstriction of pig prostatic small arteries. Naunyn Schmiedebergs Arch Pharmacol. 2008;376:397-406. https://doi.org/10.1007/s00210-007-0227-x
  26. Whorlow SL, Angus JA, Wright CE. Selectivity of omegaconotoxin GVIA for n-type calcium channels in rat isolated small mesenteric arteries. Clin Exp Pharmacol Physiol. 1996; 23:16-21. https://doi.org/10.1111/j.1440-1681.1996.tb03036.x
  27. Chien EK, Sweet L, Phillippe M, Marietti S, Kim TT, Wolff DA, Thomas L, Bieber E. Protease-activated receptor isoform expression in pregnant and nonpregnant rat myometrial tissue. J Soc Gynecol Investig. 2003;10:460-468. https://doi.org/10.1016/S1071-5576(03)00148-5
  28. Hwa JJ, Ghibaudi L, Williams P, Chintala M, Zhang R, Chatterjee M, Sybertz E. Evidence for the presence of a proteinase-activated receptor distinct from the thrombin receptor in vascular endothelial cells. Circ Res. 1996;78:581-588. https://doi.org/10.1161/01.RES.78.4.581
  29. Hamilton JR, Nguyen PB, Cocks TM. Atypical protease-activated receptor mediates endothelium-dependent relaxation of human coronary arteries. Circ Res. 1998;82:1306-1311. https://doi.org/10.1161/01.RES.82.12.1306
  30. Roy SS, Saifeddine M, Loutzenhiser R, Triggle CR, Hollenberg MD. Dual endothelium-dependent vascular activities of proteinase- activated receptor-2-activating peptides: evidence for receptor heterogeneity. Br J Pharmacol. 1998;123:1434-1440. https://doi.org/10.1038/sj.bjp.0701726
  31. Sobey CG, Moffatt JD, Cocks TM. Evidence for selective effects of chronic hypertension on cerebral artery vasodilatation to protease-activated receptor-2 activation. Stroke. 1999;30:1933-1940 https://doi.org/10.1161/01.STR.30.9.1933
  32. McGuire JJ. Proteinase-activated Receptor 2 (PAR2): a challenging new target for treatment of vascular diseases. Curr Pharm Des. 2004;10:2769-2778. https://doi.org/10.2174/1381612043383656
  33. Camerer E, Cornelissen I, Kataoka H, Duong DN, Zheng YW, Coughlin SR. Roles of protease-activated receptors in a mouse model of endotoxemia. Blood. 2006;107:3912-3921. https://doi.org/10.1182/blood-2005-08-3130
  34. McGuire JJ, Van Vliet BN, Halfyard SJ. Blood pressures, heart rate and locomotor activity during salt loading and angiotensin II infusion in protease-activated receptor 2 (PAR2) knockout mice. BMC Physiol. 2008;8:20. https://doi.org/10.1186/1472-6793-8-20
  35. Hille B. Modulation of ion-channel function by G-protein-coupled receptors. Trends Neurosci. 1994;17:531-536. https://doi.org/10.1016/0166-2236(94)90157-0

Cited by

  1. The signaling of protease-activated receptor-2 activating peptide-induced contraction in cat esophageal smooth muscle cells vol.40, pp.12, 2014, https://doi.org/10.1007/s12272-017-0975-1