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

Figures

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  Figure 1.. Comparison of blood pressure values between the WKY and SHR. The data are expressed as the mean ± standard deviation (n=6). 12-week-old SHR groups vs. the age-matched WKY groups, **P<0.01. WKY, Wistar Kyoto rat; SHRs, spontaneously hypertensive rat; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure.

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  Figure 2.. CaSR protein expression in the mesenteric artery of the WKY and SHR groups. (A) Western blot analysis and (B) densitometric analysis. The data are expressed as the mean ± standard deviation (n=7). WKY groups vs. SHR groups, *P<0.05. WKY, Wistar Kyoto rats; SHR, spontaneously hypertensive rats; CaSR, calcium-sensing receptor.

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  Figure 3.. Comparison of the contractions and diastolic amplitudes of the mesenteric artery in the WKY and SHR groups. The data are expressed as the mean ± standard deviation (n=6). (A) SHR PE vs. WKY PE groups, ##P<0.01; (B) SHR PE-E groups vs. WKY PE-E groups, #P<0.05. (C) WKY PE groups vs. WKY PE-E groups, P>0.05. (D) SHR PE groups vs. SHR PE-E groups, P>0.05. (E) SHR Ach groups vs. WKY Ach groups, ##P<0.01; (F) WKY SNP vs. SHR SNP groups, ##P<0.01. *P<0.05, **P<0.01, vs. the adjacent concentrations in each group. -E, endothelial removal; WKY, Wistar Kyoto rats; SHR, spontaneously hypertensive rats; PE, phenylephrine; Ach, acetylcholine; SNP, sodium nitroprusside.

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  Figure 4.. Effect of NPSR568 on vascular reactivity. The data are expressed as the mean ± standard deviation (n=6). (A) WKY NPS2143 groups vs. SHR NPS2143 groups, P>0.05; (B) WKY NPSR568 groups vs. SHR NPSR568 groups, ##P<0.01; (C) SHR PE groups vs. SHR PE + NPSR568 (1 µM) groups, #P<0.05; ##P<0.01, vs. SHR PE + NPSR568 (10 µM) group. (D) SHR PE + NPSR568-E (10 µM) groups vs. SHR PE-E groups, ##P<0.01; (E) SHR Ach group vs. SHR Ach + NPSR568 (1 µM) group, #P<0.05; ##P<0.01, vs. SHR Ach + NPSR568 (10 µM) groups. (F) SHR SNP group vs. SHR SNP + NPSR568 (10 µM) group, #P<0.05. *P<0.05, **P<0.01, vs. the adjacent concentrations in each group. -E, endothelial removal; WKY, Wistar Kyoto rats; SHR, spontaneously hypertensive rats; PE, phenylephrine; Ach, acetylcholine; SNP, sodium nitroprusside; NPSR568, CaSR agonists.

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  Figure 5.. Effect of the CaSR inhibitor NPS2143 on vascular reactivity of the mesenteric artery in the WKY and SHR. The data are expressed as the mean ± standard deviation (n=6). (A) WKY PE + NPS2143 groups vs. WKY PE groups, ##P<0.01; (B) SHR PE groups vs. SHR PE + NPS2143 groups, ##P<0.01; (C) WKY PE + NPS2143 groups vs. SHR PE + NPS2143 groups, ##P<0.01; (D) WKY PE + NPS2143 groups vs. WKY PE + NPS2143-E groups, #P<0.05; (E) SHR PE + NPS2143 groups vs. SHR PE + NPS2143-E groups, ##P<0.01; (F) WKY PE + NPS2143-E groups vs. SHR PE + NPS2143-E groups, #P<0.05; (G) WKY Ach groups vs. WKY Ach + NPS2143 groups, ##P<0.01; (H) SHR Ach groups vs. SHR Ach + NPS2143 groups, ##P<0.01; (I) WKY Ach + NPS2143 groups vs. SHR Ach + NPS2143 groups, # P<0.05; (J) WKY SNP groups vs. WKY SNP + NPS2143 groups, ##P<0.01; (K) SHR SNP groups vs. SHR SNP+NPS2143 groups, ##P<0.01; (L) WKY SNP + NPS2143 groups vs. SHR SNP + NPS2143 groups, ##P<0.01. *P<0.05, **P<0.01, vs. the adjacent concentrations in each group. -E, endothelial removal; WKY, Wistar Kyoto rats; SHR, spontaneously hypertensive rats; PE, phenylephrine; Ach, acetylcholine; SNP, sodium nitroprusside; NPS2143, CaSR inhibitor.

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  Figure 6.. Effect of PLC-IP3/AC-V/cAMP/RAS pathway inhibitors on vascular reactivity of the mesenteric artery in the WKY and SHR. The data are expressed as the mean ± standard deviation (n=6). (A) WKY PE groups vs. each signalling pathway inhibitor group, ##P<0.01; (B) SHR PE groups vs. each signalling pathway inhibitor group, ##P<0.01; (C) WKY PE-E groups vs. each signalling pathway inhibitor group, ##P<0.01; (D) SHR PE-E groups vs. each signalling pathway inhibitor group, ##P<0.01; (E) WKY Ach groups vs. each signalling pathway inhibitor group, ##P<0.01; (F) SHR Ach group vs. U73122 groups, #P<0.05; SHR Ach group vs. MDL12330A, CAP, LOS groups, ##P<0.01; (G) WKY SNP groups vs. each signalling pathway inhibitor group, ##P<0.01; (H) SHR SNP groups vs. each signalling pathway inhibitor group, ##P<0.01. *P<0.05, **P<0.01, vs. the adjacent concentrations in each group. -E, endothelial removal; WKY, Wistar Kyoto rats; SHR, spontaneously hypertensive rats; PE, phenylephrine; Ach, acetylcholine; SNP, sodium nitroprusside; PLC, phospholipase C; U73122, PLC inhibitor; 2-APB, 2-aminoethoxydiphenyl borate, IP3 inhibitor; MDL12330A, adenylyl cyclase V inhibitor; CAP, captopril, ACE inhibitor; LOS,…

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  Figure 7.. Effect of CaSR inhibitors combined with PLC-IP3/AC-V/cAMP/RAS pathway inhibitor on vascular reactivity of the MA in the WKY and SHR. The data are expressed as the mean ± standard deviation (n=6). (A) WKY PE + NPS2143 groups vs. each signalling pathway blocker group, ##P<0.01; (B) SHR PE + NPS2143 groups vs. each signalling pathway blocker group, ##P<0.01; (C) In WKY Ach + NPS214 groups vs. each signalling pathway blocker group, ##P<0.01; (D) SHR Ach + NPS2143 groups vs. each signalling pathway blocker group, ##P<0.01. *P<0.05, **P<0.01, vs. the adjacent concentrations in each group. NPS2143, CaSR inhibitor; PLC, phospholipase C; U73122, PLC inhibitor; 2-APB, 2-aminoethoxydiphenyl borate, IP3 inhibitor; MDL12330A, adenylyl cyclase V inhibitor; CAP, captopril, ACE inhibitor; LOS, losartan, AT1R inhibitor.

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  Figure 8.. Hypothetical mechanism is the calcium sensing receptor participates in the regulation of vascular tension in the mesentery of hypertensive rats via the PLC- IP3/AC-V/cAMP/RAS pathway. CaSR, calcium sensing receptor; PLC, phospholipase C; IP3, inositol 1,4,5-triphosphate; AC-V, adenylate cyclase-V; cAMP, cyclic adenosine monophosphate; RAS, renin-angiotensin system; AT1R, angiotensin II receptor type 1; [Ca2+]o, increased extracellular Ca2+; [Ca2+]i, intracellular Ca2+; NPS2143, calcium sensing receptor inhibitor; DAG, diphosphoglycerate; ER, endoplasmic reticulum; IP3R, inositol 1,4,5-triphosphate receptor; ATP, adenosine triphosphate; Gq11, G protein-coupled receptor.