Open Access

CaSR participates in the regulation of vascular tension in the mesentery of hypertensive rats via the PLC‑IP3/AC‑V/cAMP/RAS pathway

  • Authors:
    • Wenwen Zhang
    • Ruixia Sun
    • Hua Zhong
    • Na Tang
    • Yongmin Liu
    • Yongli Zhao
    • Tian Zhang
    • Fang He
  • View Affiliations

  • Published online on: August 27, 2019     https://doi.org/10.3892/mmr.2019.10620
  • Pages: 4433-4448
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypertension is a cardiovascular disease that severely impairs human health; however, its specific etiology and pathogenesis are complex. The present study investigated the effects of the calcium sensing receptor (CaSR) on vascular tone in spontaneously hypertensive rats (SHRs), and clarified the role and mechanism of CaSR in regulating this property with respect to the phospholipase C (PLC)‑inositol 1,4,5‑triphosphate (IP3)/adenylate cyclase‑V(AC‑V)/cyclic adenosine monophosphate (cAMP)/renin‑angiotensin system (RAS) pathway in these animals. CaSR protein expression in the mesenteric artery (MA) of rats and CaSR protein expression in SHRs were significantly reduced. Based on wire myography studies, vasoconstriction was significantly augmented and vasodilatation was attenuated in SHRs, and this effect was endothelium‑independent. The CaSR calcimimetic NPSR568 and inhibitor NPS2143 reduced vasoconstriction and enhanced vasodilation in SHRs. Furthermore, pretreatment with PLC‑IP3/AC‑V/cAMP/RAS pathway blockers significantly reduced the vasoconstriction response and enhanced the vasodilator response in SHRs and Wistar‑Kyoto rats (WKY), and these effects were partially dependent on the endothelium. Additionally, pretreatment with CaSR inhibitors were determined to cooperate with the PLC‑IP3/AC‑V/cAMP/RAS pathway inhibitors to significantly reduce vasoconstriction and enhance vasodilation in SHRs and WKY. Our results demonstrated that CaSR is functionally expressed in the MA of SHRs, and that CaSR expression is decreased in SHRs. Additionally, vasoconstriction was enhanced while vasodilatation was attenuated in SHRs; these processes were determined to be endothelium‑independent. CaSR is involved in the regulation of blood pressure and vascular tension in SHRs and WKYs. In association with mechanistic differences, this effect was proposed to be partially endothelium‑dependent and mediated by the PLC‑IP3/AC‑V/cAMP/RAS pathway.
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November-2019
Volume 20 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhang W, Sun R, Zhong H, Tang N, Liu Y, Zhao Y, Zhang T and He F: CaSR participates in the regulation of vascular tension in the mesentery of hypertensive rats via the PLC‑IP3/AC‑V/cAMP/RAS pathway . Mol Med Rep 20: 4433-4448, 2019
APA
Zhang, W., Sun, R., Zhong, H., Tang, N., Liu, Y., Zhao, Y. ... He, F. (2019). CaSR participates in the regulation of vascular tension in the mesentery of hypertensive rats via the PLC‑IP3/AC‑V/cAMP/RAS pathway . Molecular Medicine Reports, 20, 4433-4448. https://doi.org/10.3892/mmr.2019.10620
MLA
Zhang, W., Sun, R., Zhong, H., Tang, N., Liu, Y., Zhao, Y., Zhang, T., He, F."CaSR participates in the regulation of vascular tension in the mesentery of hypertensive rats via the PLC‑IP3/AC‑V/cAMP/RAS pathway ". Molecular Medicine Reports 20.5 (2019): 4433-4448.
Chicago
Zhang, W., Sun, R., Zhong, H., Tang, N., Liu, Y., Zhao, Y., Zhang, T., He, F."CaSR participates in the regulation of vascular tension in the mesentery of hypertensive rats via the PLC‑IP3/AC‑V/cAMP/RAS pathway ". Molecular Medicine Reports 20, no. 5 (2019): 4433-4448. https://doi.org/10.3892/mmr.2019.10620