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Beneficial Cardiovascular Effects Of Hydroalcoholic Extract From Crocus Sativus In Hypertension Induced By Angiotensin II

  • Plangar, Abdolali Faramarzi ;
  • Anaeigoudari, Akbar ;
  • KhajaviRad, Abolfazl ;
  • Shafei, Mohammad Naser
  • Received : 2017.11.14
  • Accepted : 2019.05.20
  • Published : 2019.06.28

Abstract

Objectives: Angiotensin II (AngII), a major product of renin-angiotensin system (RAS) has important role in induction of hypertension and antihypertensive effect of several medicinal plant was mediated by effect on this agent. Therefore, this study examined the possible effect of hydroalcoholic extract of Crocus sativus (C. sativus) on hypertension induced by AngII. Methods: Six groups (n = 6) of rats were used as follow: 1) Control, 2) AngII (300 ng/kg), 3) Losartan (Los, 10 mg/kg) + AngII and 4-6) C. sativus extract (10, 20 & 40 mg/kg,) + AngII. The femoral artery and vein were cannulated for recording cardiovascular parameters and drugs administration, respectively. All drugs were injected intravenously (i.v). Los and all doses of C. sativus injected 10 min before AngII. Systolic blood pressure (SBP), mean arterial blood pressure (MAP) and heart rate (HR) were recorded throughout the experiment and those peak changes (${\Delta}$) were calculated and compared to control and AngII. Results: AngII significantly increased ${\Delta}MAP$, ${\Delta}SBP$ and ${\Delta}HR$ than control (P < 0. 01 to P < 0.001) and these increments were significantly attenuated by Los. All doses of C. sativus significantly reduced peak ${\Delta}MAP$, ${\Delta}SBP$, and ${\Delta}HR$ than AngII group (P < 0. 05 to P < 0.001). In addition, peak ${\Delta}MAP$, ${\Delta}SBP$ in doses 10 and 20 were significant than Los + AngII group (P<0.05 to P< 0.01) but in dose 40 only MAP was significant (P<0.05). Peak ${\Delta}HR$ in all doses of C sativus was not significant than Los+ AngII. Conclusion: Regarding the improving effect of the C. sativus extract on AngII induced hypertension, it seems that this ameliorating effect partly mediated through inhibition of RAS.

Keywords

angiotensin II;crocus sativus;hypertension;blood pressure;heart rate

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Figure 1 A sample of cardiovascular responses recorded record after intravenous injection 300 mg/kg of AngII. Injection time marked by a vertical line

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Figure 1 A sample of cardiovascular responses recorded record after intravenous injection 300 mg/kg of AngII. Injection time marked by a vertical line

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Figure2 Peak changes of SBP (A), MAP (B), and HR (C) after infusion 300 ng/kg of AngII and Losartan (Los; 10 mg/kg) + AngII. Expression of Data: mean ± SEM (n = 6); Statistical analysis: One-way ANOVA with Tukey’s post hoc; *p < 0.05, **P < 0.01 and ***p < 0.001 vs control; ++p < 0.01, +++p < 0.001 vs AngII 300 MAP: mean arterial pressure; SBP: systolic blood pressure; HR: heart rate

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Figure2 Peak changes of SBP (A), MAP (B), and HR (C) after infusion 300 ng/kg of AngII and Losartan (Los; 10 mg/kg) + AngII. Expression of Data: mean ± SEM (n = 6); Statistical analysis: One-way ANOVA with Tukey’s post hoc; *p < 0.05, **P < 0.01 and ***p < 0.001 vs control; ++p < 0.01, +++p < 0.001 vs AngII 300 MAP: mean arterial pressure; SBP: systolic blood pressure; HR: heart rate

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Figure 3 Comparison peak changes of MAP induced by i.v injection of 3 doses of C. sativus extract (10, 20 & 40 mg/kg) + AngII with AngII alone and Los + AngII groups. Expression of Data: mean ± SEM (n = 6). Statistical analysis: One-way ANOVA with Tukey’s post hoc;* P < 0.05, ** P < 0.01 and *** p < 0.001 vs AngII; ++p < 0.01, +++p < 0.001 vs AngII + Los MAP: mean arterial pressure

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Figure 3 Comparison peak changes of MAP induced by i.v injection of 3 doses of C. sativus extract (10, 20 & 40 mg/kg) + AngII with AngII alone and Los + AngII groups. Expression of Data: mean ± SEM (n = 6). Statistical analysis: One-way ANOVA with Tukey’s post hoc;* P < 0.05, ** P < 0.01 and *** p < 0.001 vs AngII; ++p < 0.01, +++p < 0.001 vs AngII + Los MAP: mean arterial pressure

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Figure 4 Comparison peak changes of SBP induced by i.v injection of 3 doses of C. sativus extract (10, 20 & 40 mg/kg) + AngII with AngII alone and Los + AngII groups. Expression of Data: mean ± SEM (n = 6). Statistical analysis: One-way ANOVA with Tukey’s post hoc; *P < 0.05, **P < 0.01 and ***p < 0.001 vs AngII; +p < 0.05, ++p < 0. 01 vs AngII + Los; SBP: systolic blood pressure

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Figure 4 Comparison peak changes of SBP induced by i.v injection of 3 doses of C. sativus extract (10, 20 & 40 mg/kg) + AngII with AngII alone and Los + AngII groups. Expression of Data: mean ± SEM (n = 6). Statistical analysis: One-way ANOVA with Tukey’s post hoc; *P < 0.05, **P < 0.01 and ***p < 0.001 vs AngII; +p < 0.05, ++p < 0. 01 vs AngII + Los; SBP: systolic blood pressure

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Figure 5 Comparison peak changes of HR induced by i.v injection of 3 doses of C. sativus extract (10, 20 & 40 mg/kg) + AngII with AngII alone and Los + AngII groups. Expression of Data: mean ± SEM (n = 6). Statistical analysis: One-way ANOVA with Tukey’s post hoc; *P < 0.05, **P < 0.01 vs AngII; HR: heart rate

DHOCBS_2019_v22n2_95_f0005.png 이미지

Figure 5 Comparison peak changes of HR induced by i.v injection of 3 doses of C. sativus extract (10, 20 & 40 mg/kg) + AngII with AngII alone and Los + AngII groups. Expression of Data: mean ± SEM (n = 6). Statistical analysis: One-way ANOVA with Tukey’s post hoc; *P < 0.05, **P < 0.01 vs AngII; HR: heart rate

References

  1. Xie Y, Zhang W. Antihypertensive activity of Rosa rugosa Thunb. flowers: angiotensin I converting enzyme inhibitor. J Ethnopharmacol. 2012;144(3):562-566. https://doi.org/10.1016/j.jep.2012.09.038
  2. Sliwa K, Stewart S, Gersh BJ. Hypertension: a global perspective. Circulation. 2011;123(24):2892-2896. https://doi.org/10.1161/CIRCULATIONAHA.110.992362
  3. Moraes PL, Kangussu LM, Silva LG, Castro CH, Santos RA, Ferreira AJ. Cardiovascular effects of small peptides of the renin angiotensin system. Physiol Rep. 2017;5(22):e13505.
  4. Navar LG, Prieto MC, Satou R, Kobori H. Intrarenal angiotensin II and its contribution to the genesis of chronic hypertension. Curr Opin Pharm. 2011;11(2):180-186. https://doi.org/10.1016/j.coph.2011.01.009
  5. Xue H, Lu Z, Tang W, Pang L, Wang G, Wong G, et al. First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. Cochrane Database Syst Rev. 2018;2018(11):CD008170.
  6. Hilzendeger AM, Morgan DA, Brooks L, Dellsperger D, Liu X, Grobe JL, et al. A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity. Am J Physiol Heart Circ Physiol. 2012;303(2):H197-H206. https://doi.org/10.1152/ajpheart.00974.2011
  7. Ylitalo A, Airaksinen KJ, Hautanen A, Kupari M, Carson M, Virolainen J, et al. Baroreflex sensitivity and variants of the renin angiotensin system genes. J Am Coll Cardiol. 2000;35(1):194-200. https://doi.org/10.1016/S0735-1097(99)00506-9
  8. Shafei MN, Faramarzi A, Rad AK, Anaeigoudari A. Crocin prevents acute angiotensin II-induced hypertension in anesthetized rats. Avicenna J Phytomed. 2017;7(4):345.
  9. Serrano-Diaz J, Sanchez AM, Martinez-Tome M, Winterhalter P, Alonso GL. A contribution to nutritional studies on Crocus sativus flowers and their value as food. J Food Compost Anal. 2013;31(1):101-108. https://doi.org/10.1016/j.jfca.2013.03.009
  10. Bhargava V. Medicinal uses and pharmacological properties of Crocus sativus linn (saffron). Int J Pharm Pharm Sci. 2011;3(Suppl 3):22-26.
  11. Jose Bagur M, Alonso Salinas GL, Jimenez-Monreal AM, Chaouqi S, Llorens S, Martinez-Tome M, et al. Saffron: An Old Medicinal Plant and a Potential Novel Functional Food. Molecules. 2017;23(1):30. https://doi.org/10.3390/molecules23010030
  12. Wang Y, Sun J, Liu C, Fang C. Protective effects of crocetin pretreatment on myocardial injury in an ischemia/reperfusion rat model. Eur J Pharmacol. 2014;741:290-296. https://doi.org/10.1016/j.ejphar.2014.07.052
  13. Imenshahidi M, Hosseinzadeh H, Javadpour Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res. 2010;24(7):990-994. https://doi.org/10.1002/ptr.3044
  14. Shafei MN, Nasimi A. Effect of glutamate stimulation of the cuneiform nucleus on cardiovascular regulation in anesthetized rats: Role of the pontine Kolliker-Fuse nucleus. Brain Res. 2011;1385:135-143. https://doi.org/10.1016/j.brainres.2011.02.046
  15. Nasimi A, Shafei M, Alaei H. Glutamate injection into the cuneiform nucleus in rat, produces correlated single unit activities in the Kolliker-Fuse nucleus and cardiovascular responses. Neuroscience. 2012;223:439-446.
  16. Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. American Journal of Physiology-Cell Physiology. 2007;292(1):C82-C97. https://doi.org/10.1152/ajpcell.00287.2006
  17. Touyz RM, Schiffrin EL. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev. 2000;52(4):639-672.
  18. Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, et al. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci. 2006;103(47):17985-17990. https://doi.org/10.1073/pnas.0605545103
  19. Enayatfard L, Mohebbati R, Niazmand S, Hosseini M, Shafei MN. The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats. J Basic Clin Physiol Pharmacol. 2018;30(1):51-58. https://doi.org/10.1515/jbcpp-2018-0074
  20. Srivastava R, Ahmed H, Dixit R. Crocus sativus L.: a comprehensive review. Pharmacogn Rev. 2010;4(8):200. https://doi.org/10.4103/0973-7847.70919
  21. Mehdizadeh R, Parizadeh MR, Khooei A-R, Mehri S, Hosseinzadeh H. Cardioprotective effect of saffron extract and safranal in isoproterenol-induced myocardial infarction in wistar rats. Iran J Basic Med Sci. 2013;16(1):56.
  22. Assimopoulou A, Sinakos Z, Papageorgiou V. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res. 2005;19(11):997-1000. https://doi.org/10.1002/ptr.1749
  23. Zheng Y-Q, Liu J-X, Wang J-N, Xu L. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res. 2007;1138:86-94. https://doi.org/10.1016/j.brainres.2006.12.064
  24. Bountagkidou O, van der Klift EJ, Tsimidou MZ, Ordoudi SA, van Beek TA. An on-line high performance liquid chromatography-crocin bleaching assay for detection of antioxidants. J Chromatogr. 2012;1237:80-85. https://doi.org/10.1016/j.chroma.2012.03.026
  25. Zheng S, Qian Z, Wen N, Xi L. Crocetin suppresses angiotensin II-induced vascular smooth-muscle cell proliferation through inhibition of ERK1/2 activation and cell-cycle progression. J Cardiovasc Pharmacol. 2007;50(5):519-525. https://doi.org/10.1097/FJC.0b013e31813c114e
  26. Imenshahidi M, Razavi BM, Faal A, Gholampoor A, Mousavi SM, Hosseinzadeh H. The effect of chronic administration of safranal on systolic blood pressure in rats. Iran J Pharm Res. 2015;14(2):585.
  27. Schulman IH, Zhou M-S, Raij L. Interaction between nitric oxide and angiotensin II in the endothelium: role in atherosclerosis and hypertension. J Hypertens. 2006;24:S45-S50. https://doi.org/10.1097/01.hjh.0000220406.46246.f2
  28. Landmesser U, Cai H, Dikalov S, McCann L, Hwang J, Jo H, et al. Role of p47phox in vascular oxidative stress and hypertension caused by angiotensin II. Hypertension. 2002;40(4):511-515. https://doi.org/10.1161/01.HYP.0000032100.23772.98
  29. Nickenig G, Harrison DG. The AT1-type angiotensin receptor in oxidative stress and atherogenesis: part II:AT1 receptor regulation. Circulation. 2002;105(4):530-536. https://doi.org/10.1161/hc0402.102619
  30. Stegbauer J, Lee D-H, Seubert S, Ellrichmann G, Manzel A, Kvakan H, et al. Role of the renin-angiotensin system in autoimmune inflammation of the central nervous system. Proc Natl Acad Sci. 2009;106(35):14942-14947.
  31. Muller DN, Shagdarsuren E, Park J-K, Dechend R, Mervaala E, Hampich F, et al. Immunosuppressive treatment protects against angiotensin II-induced renal damage. Am J Pathol. 2002;161(5):1679-1693. https://doi.org/10.1016/S0002-9440(10)64445-8
  32. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, et al. Role of the T cell in the genesis of angiotensin II-induced hypertension and vascular dysfunction. J Exp Med. 2007;204(10):2449-2460. https://doi.org/10.1084/jem.20070657
  33. Peng F, Lin J, Lin L, Tang H. Transient prehypertensive treatment in spontaneously hypertensive rats: A comparison of losartan and amlodipine regarding longterm blood pressure, cardiac and renal protection. Int J Mol Med. 2012;30(6):1376-1386. https://doi.org/10.3892/ijmm.2012.1153
  34. Wang T, Lian G, Cai X, Lin Z, Xie L. Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high-fat-fed spontaneously hypertensive rats. Mol Med Report. 2018;17(1):1753-1761.
  35. Ghods R, Gharouni M, Amanlou M, Sharifi N, Ghobadi A, Amin G. Effect of Onopordon acanthium L. as Add on Antihypertensive Therapy in Patients with Primary Hypertension Taking Losartan: a Pilot Study. Adv Pharm Bull. 2018;8(1):69. https://doi.org/10.15171/apb.2018.009
  36. Tsunoda K, Abe K, Hagino T, Omata K, Misawa S, Imai Y, et al. Hypotensive effect of losartan, a nonpeptide angiotensin II receptor antagonist, in essential hypertension. Am J Hypertens. 1993;6(1):28-32. https://doi.org/10.1093/ajh/6.1.28

Acknowledgement

Supported by : Council of Mashhad University of Medical Science