Crocin prevents acute angiotensin II-induced hypertension in anesthetized rats

Document Type : Original Research Article

Authors

1 Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Neurogenic Inflammation Research Center, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Physiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran

Abstract

Objective: Angiotensin II (Ang II), the main product of renin-angiotensin system (RAS) has a well-known role in cardiovascular regulation. Over-production of Ang II is one of the important underlying mechanisms of hypertension. In this study, the effect of crocin on cardiovascular responses in rats with acute hypertension induced by Ang II was evaluated.
Materials and methods: Rats were divided into six groups (n = 6): 1) Control: rats that received saline, 2) Ang II: rats that received Ang II (300 ng/kg) infused in two min, 3) Losartan (Los) + Ang II : rats that received Los (10 mg/kg, i.v) before Ang II, and 4-6) Crocin (Cro) + Ang II groups: rats that received three doses of crocin (50, 100 and 200 mg/kg, slow i.v) 10 min before Ang II. Femoral artery and vein were cannulated for recording of cardiovascular parameters and injection of drugs, respectively. Systolic blood pressure (SBP), mean arterial blood pressure (MAP) and heart rate (HR) were continuously recorded by power lab system. After injection of reagents and extracts, maximum changes (∆) of MAP, SBP and HR were recorded and compared with control group.
Results: Ang II (300 ng/kg) increased maximal changes in MAP, SBP and HR compared to control group (p<0.001) and Los significantly attenuated these effects of Ang II (p<0.001). Maximal changes of MAP, SBP and HR induced by Ang II, were significantly attenuated by pretreatment with all doses of crocin (50,100 and 200) (p Conclusion: Based on the effects of crocin on acute Ang II-induced hypertension, it is hypothesized that the cardiovascular improving effects of crocin may be mediated via suppressing of RAS.

Keywords

Main Subjects


Abe K, Saito H. 2000. Effects of saffron extract and its constituent crocin on learning behaviour and long‐term potentiation. Phytother Res, 14:149-152
Asdaq SMB, Inamdar MN, 2010. Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats. Appl biochem biotechnol, 162:358-372
Boskabady M, Shafei M, Shakiba A, Sefidi HS 2008. Effect of aqueous‐ethanol extract from Crocus sativus (saffron) on guinea‐pig isolated heart. Phytother Res, 22:330-334
Bruner CA, Fink GD 1985. Cerebroventricular infusion of angiotensin antagonist does not influence hypertensive response to blood-borne angiotensin II. Brain Res, 360:15-23
Carey RM, Siragy HM 2003. Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev, 24:261-271
Crowley SD, Gurley SB, Herrera MJ, et al. 2006. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Nati Acad Sci, 103:17985-17990
He S-Y, Qian Z-Y, Tang F-T 2004. Effect of crocin on intracellular calcium concentration in cultured bovine aortic smooth muscle cells. Yao xue xue bao, 39:778-781
Hosseinzadeh H, Shamsaie F, Mehri S 2009. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal. Pharmacog Mag, 5:419
Hosseinzadeh H, Talebzadeh F 2005. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia, 76:722-724
Ibrahim MM 2006. RAS inhibition in hypertension. J Hum Hhypertens, 20:101-108
Imenshahidi M, Hosseinzadeh H, Javadpour Y 2010. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res, 24:990-994
Imenshahidi M, Razavi BM, Faal A, Gholampoor A, Mousavi SM, Hosseinzadeh H 2014a. Effects of chronic crocin treatment on desoxycorticosterone acetate (doca)-salt hypertensive rats. Iran J Basic Med Sci, 17:9-13
Imenshahidi M, Razavi BM, Faal A, Gholampoor A, Mousavi SM, Hosseinzadeh H 2014b. Effects of chronic crocin treatment on desoxycorticosterone acetate (doca)-salt hypertensive rats. Iran J Basic Med Sci, 17:9-13
Khazdair MR, Boskabady MH, Hosseini M, Rezaee R, Tsatsakis AM. 2015. The effects of Crocus sativus (saffron) and its constituents on nervous system: A review. Avicenna J Phytomed, 5: 376-391.
Laursen JB, Rajagopalan S, Galis Z, Tarpey M, Freeman BA, Harrison DG 1997. Role of superoxide in angiotensin II–induced but not catecholamine-induced hypertension. Circulation, 95:588-593
Lavoie JL, Sigmund CD 2003. Minireview: overview of the renin-angiotensin system—an endocrine and paracrine system. Endocrinology, 144:2179-2183
Mahmoudabady M, Shafei MN, Niazmand S, Khodaee 2014. The effects of hydroalchoholic extract of Teucrium polium L. on hypertension induced by angiotensin II in rats. Int J Prev Med, 5:1255
Mancini A, Serrano-Díaz J, Nava E, et al. 2014. Crocetin, a carotenoid derived from saffron (Crocus sativus L.), improves acetylcholine-induced vascular relaxation in hypertension. J Vasc Res, 51:393-404
Mehta PK, Griendling KK 2007. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol, 292:C82-C97
Mokhtari-Zaer A, Khazdair MR, Boskabady MH. 2015. Smooth muscle relaxant activity of Crocus sativus (saffron) and its constituents: possible mechanisms. Avicenna J Phytomed, 5: 365-375.
Mollnau H, Wendt M, Szöcs K, et al. 2002. Effects of angiotensin II infusion on the expression and function of NAD (P) H oxidase and components of nitric oxide/cGMP signaling. Circ Res, 90:e58-e65
Patten GS, Abeywardena MY 2017. Effects of Antihypertensive Agents on Intestinal Contractility in the Spontaneously Hypertensive Rat: Angiotensin Receptor System Downregulation by Losartan. J  Pharmacol Exp Ther, 360:260-266
Perez YY, Jimenez-Ferrer E, Alonso D, Botello-Amaro CA, Zamilpa A 2010. Citrus limetta leaves extract antagonizes the hypertensive effect of angiotensin II. J ethnopharmacol, 128:611-614
Rajagopalan S, Kurz S, Münzel T, et al. 1996. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest, 97:1916
Razavi BM, Hosseinzadeh H, Movassaghi AR, Imenshahidi M, Abnous K 2013a. Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure. Chem Biol Interac, 203:547-555
Razavi M, Hosseinzadeh H, Abnous K, Motamedshariaty VS, Imenshahidi M 2013b. Crocin restores hypotensive effect of subchronic administration of diazinon in rats. Iran J Basic Med Sci, 16:64
Shafei MN, Niazmand S, Hosseini M, Daloee MH 2013. Pharmacological study of cholinergic system on cardiovascular regulation in the cuneiform nucleus of rat. Neurosci lett, 549:12-17
Srivastava R, Ahmed H, Dixit R 2010. Crocus sativus L.: a comprehensive review. Pharmacogn Rev, 4:200
Stegbauer J, Lee D-H, Seubert S, et al. 2009. Role of the renin-angiotensin system in autoimmune inflammation of the central nervous system. Proc Nati Acad  Sci, 106:14942-14947
Taubman MB, Berk BC, Izumo S, Tsuda T, Alexander RW, Nadal-Ginard B 1989. Angiotensin II induces c-fos mRNA in aortic smooth muscle. Role of Ca2+ mobilization and protein kinase C activation. J Biol Chem, 264:526-530
Touyz RM 2003. Recent advances in intracellular signalling in hypertension. Curr Opin Nephrol Hypertens, 12:165-174
Touyz RM, Schiffrin EL 2000. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev, 52:639-672
Tsunoda K, Abe K, Hagino T, et al. 1993. Hypotensive effect of losartan, a nonpeptide angiotensin II receptor antagonist, in essential hypertension. Am J Hypertens, 6:28-32
Veerasingham SJ, Raizada MK 2003. Brain renin–angiotensin system dysfunction in hypertension: recent advances and perspectives. Br J pharmacol, 139:191-202
Wong PC, Price W, Chiu AT, et al. 1990a. Nonpeptide angiotensin II receptor antagonists. XI. Pharmacology of EXP3174: an active metabolite of DuP 753, an orally active antihypertensive agent. J Pharmacol Exp Ther, 255:211-217
Wong PC, Price WA, Chiu AT, et al. 1990b. Nonpeptide angiotensin II receptor antagonists. Studies with EXP9270 and DuP 753. Hypertension, 15:823-834
Xie Y, Zhang W 2012. Antihypertensive activity of Rosa rugosa Thunb. flowers: angiotensin I converting enzyme inhibitor. J Ethnopharmacol, 144:562-6
Zheng Y-Q, Liu J-X, Wang J-N, Xu L 2007 Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res, 1138:86-94
Zimmerman MC, Lazartigues E, Sharma RV, Davisson RL 2004.∆ Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circ Res, 95:210-216