@2024 Afarand., IRAN

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ISSN: 2252-0805    The Horizon of Medical Sciences 2018;24(4):309-315

Background
Hypertension is one of the most common and important health issues that has affected the lives of millions of people around the world [1].
Previous Studies
Hypertension can lead to severe complications, such as kidney disease and arthroplastic complications, including stroke, coronary artery disease, renal and heart failure [2]. ... [3, 4]. Researchers have shown that both topical and systemic renin-angiotensin systems can affect the function of the cardiovascular system [5]. ... [6-13]. Crocin is a carotenoid compound that produces yellowish-golden food and has beneficial effects, such as anti-tumor, lipid lowering, antioxidant, and memory and learning enhancement effects [12, 14, 15]. In addition, saffron extract and its active compounds, including crocin and crocetin have protective effects on the cardiovascular system [16]. ... [17, 18].
Aim(s)
In this study, the effect of intraperitoneal (ip) injection of Crocin on hypertension induced by angiotensin II (Ang II) with dose of 50 ng/kg was investigated in rats.
Research type
The present research is an experimental study.
Research society, place and time
This experimental study was conducted on male rats in Mashhad during 2014 to 2015.
Sampling method and number
In this experimental study, 30 male rats (weighing 200±10 g) purchased from animal house of Mashhad University of Medical Sciences were used.
Used devices&materials
Animals were kept under standard conditions (12: 12 light-dark cycle, temperature 2±20°C) with free access to water and food. Experiments on animals were carried out according to the instructions approved by the Laboratory Ethics Committee of the Laboratory of Animals of Mashhad University of Medical Sciences (Ethics code: 900559). Animals were randomly divided into 5 groups as follows (6 rats in each group): Control group (Cont), Angiotensin II (Ang II 50 ng/kg), Losartan 10+Angiotensin II (Los+Ang II) and two groups of crocin+angiotensin II (Cro100+Ang II and Cro200+Ang II). In the control group, saline was injected intravenously as a solvent. In the Losartan group, Losartan (Dropakhsh; Iran) at a dose of 10 mg/kg was injected intravenously 2 min before injection of angiotensin II. In Ang II +crocin groups, Ang II (Sigma-Aldrich, USA) was injected (50 ng/kg) intravenously. In crocin groups, crocin was injected intraperitoneally at 100 and 200 mg/kg [4, 17] 30 min before injection of Ang II. Animals were first anesthetized by urethane (Sigma-Aldrich, USA) at 1.5 g/kg followed by additional dose of 0.7 g/kg by intraperitoneal injection. To record the blood pressure and heart rate, the femoral artery was cannulated by a polyethylene (PE=50) catheter filled with a heparinized saline (50 u/ml). In order to place the arterial catheter, the animal was placed on the surgical table on its back and a cut was made in the inner thigh of the left thigh using a cutter. After clearing the area, the artery and femoral vein were identified and carefully separated from the vein. Then, by pulling the forceps over the arteries, it was filled by blood, and after making a small cut on the artery, the catheter was inserted into the artery and fixed to the animal's body by suture 4-0. The arterial catheter was then connected to a transducer. Femoral vein cannulation was done to inject the drug similar to the arteries. Following successful cannulation, changes in systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded using Power Lab apparatus (AD instrument, Australia) and the LabChart 7. In this study, Ang II intravenous injection was used to induce hypertension based on previous studies [4]. In summary, Ang II (50 ng/kg) was infused for 2 min to induce a constant and high blood pressure. Before injections, the arterial pressure and heart rate were recorded for at least 15 min in order to ensure their steady state. In crocin groups, two doses (100 and 200 mg/kg) were separately injected intraperitoneally 30 min before Ang II. Injection volume considered 0.5 ml. After injection of drugs and solvent, the maximum changes (Δ: difference before and after injection) of SBP, MAP and HR were calculated and compared. At all stages of the test, a temperature of 37°C was maintained with a lamp. The maximum changes (Δ) were obtained at various minutes and compared with repeated measures ANOVA and Tukey's post-hoc test. Maximum variation was also analyzed by t-test. SPSS 18 was used.
Findings by Text
Effect of Saline Injection on Cardiovascular Parameters Saline injection had a significant effect on SBP (before: 124.22±3.91 mmHg and after: 122.90±3.92 mmHg), MAP (before: 111.12±2.22 mmHg and after: 110.88±1.98 μg), HR (321.80±14.69 beats per min and after: 312.71±15.7 beats per min). The effect of intravenous injection of Ang II (50 ng/kg) on cardiovascular parameters Ang II injection significantly increased the maximum changes in these cardiovascular parameters in the Ang II50 group compared with the control group (P<0.001; Fig. 1a, 1b) and heart rate (P<0.01; Fig. 1c). The effect of intravenous injection of Losartan on cardiovascular parameters in angiotensin-induced hypertension The pretreatment with Losartan significantly reduced the changes in cardiovascular parameters in the Los group compared with the Ang II50 group (P<0.01). In addition, injection of Losartan before Ang II significantly reduced Ang II-induced bradycardia in the Los group compared with the Ang II50 group (p<0.05; Fig. 1a, 1b and 1c). Effects of pretreatment with crocin on Ang II-induced hypertension Intraperitoneal injection of crocin (100 and 200 mg/kg) 30 min before Ang II significantly reduced the maximum changes of SBP and MAP in Cro 100+Ang II and Cro 200+Ang II groups compared with the Ang II50 group (P<0.05 and P<0.01) (Figures 2a and 2b). Pretreatment with crosin (100 mg/kg) had no significant effect on heart rate in the Cro100+Ang II group compared with the Ang II group, whereas injection of croscin (200 mg/kg) caused a significant reduction in heart rate in the Cro200+Ang II group compared with the Ang II50 group (P<0.05; Fig. 2c).
Main comparison to the similar studies
... [19, 20]. The RAS system is a hormone regulating system for body fluids, electrolyte homeostasis and vascular tone [21]. These classical actions of the RAS system are mediated through peptide effectors, including Ang II and IV [22]. Ang II as the main factor of this system has several effects on the kidneys, adrenal glands, sympathetic nervous system, and baroreceptor reflexes [21, 23]. Also, Ang II-induced hypertension can occur by activating the phospholipase C enzyme, increasing the concentration of intracellular calcium, and reducing nitric oxide release [4, 24]. These findings confirm the results of this study, indicating that Ang II intraperitoneal injection increased cardiovascular parameters in rats. Mancini et al. have shown that the extract of saffron and its crocin increases vascular dilatation, including nitric oxide [25]. Crocin can inhibit calcium release from the vascular smooth muscle of the blood vessel networks [26]. According to these studies, it is suggested that the effect of lowering effect of crocin on the Ang-II-induced hypertension by has been mediated through at least one of these methods. ... [27-38].
Suggestions
None declared.
Limitations
None declared.
Conclusions
According to lowering effect of crocin on the Ang-II-induced hypertension, it is suggested that its effectiveness can be mediated by inhibiting Renin Angiotensin System.
Acknowledgments
The authors would like to thank the Vice-Chancellor for Research of Mashhad University of Medical Sciences for their financial support for this study.
Conflict of interest
None declared.
Ethical Permissions
None declared.
Funding Sources
This study was supported by the Vice-Chancellor of Research of Mashhad University of Medical Sciences.

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