Ruta montana evokes antihypertensive activity through increase of prosta-glandins release in L-NAME-induced hypertensive rats

2020 ◽  
Vol 20 ◽  
Author(s):  
El-Ouady Fadwa ◽  
Mohamed Eddouks
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Aqueous Extract ◽  
Antihypertensive Effect ◽  
Antihypertensive Activity ◽  
Computer Assisted ◽  
Hypertensive Rats ◽  
Vasorelaxant Effect ◽  
Vasorelaxant Activity ◽  
Ruta Montana

Aims: The aim of the study was to investigate experimentally the antihypertensive effect of Ruta Montana. Background: Ruta montana L. is traditionally used in Moroccan herbal medicine to treat hypertension. This study aimed to evaluate experimentally the hypotensive and vasoactive properties of this plant. Objective: The objective of the study was to evaluate the effect of the aqueous extract of Ruta Montana on blood pressure parameters in LNAME-induced hypertensive rats and to determine the vasorelaxant activity of this aqueous extract. Methods: The antihypertensive effect of the aqueous extract obtained from Ruta montana aerial parts (RMAPAE) (200 mg/kg) was evaluated in normal and anesthetized hypertensive rats. Blood pressure parameters (systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP)) and heart rate were measured using a tail-cuff and a computer-assisted monitoring device. The acute and chronic effect of RMAPAE was recorded during 6 hours for the acute experiment and during 7 days for the sub-chronic test. In the other set, the vasorelaxant effect of RMAPAE on the contractile response was undertaken in isolated thoracic aorta. Results: The results indicated that RMAPAE extract significantly decreased SBP, MBP, DBP and heart rate in L-NAMEinduced hypertensive rats. Furthermore, RMAPAE was demonstrated to induce a dose dependent relaxation in the aorta precontracted with Epinephrine or KCl. More interestingly, this vasorelaxant activity of RMAPAE seems to be probably mediated through the prostaglandins pathway. Conclusion: The present study illustrates the beneficial action of Ruta montana on hypertension and supports then its use as an antihypertensive agent.

Asteriscus graveolens exhibits Antihypertensive Activity through Activation of Vascular KATP Channels Activation in Rats

2020 ◽  
Vol 20 (5) ◽  
pp. 736-744
Author(s):  
Fadwa El-Ouady ◽  
Mohamed Eddouks
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Katp Channels ◽  
Antihypertensive Activity ◽  
Hypertensive Rats ◽  
Vasorelaxant Effect ◽  
Aerial Parts ◽  
In Vitro Investigation ◽  
Vasorelaxant Activity

Objective: The objective of the study was to evaluate the antihypertensive activity of Asteriscus graveolens. Methods: L-NAME hypertensive and normotensive rats have received orally the aqueous extract of Asteriscus graveolens aerial parts (AGAPE) (100 mg/kg) during six hours for the acute experiment and during seven days for the sub-chronic treatment. Thereafter, blood pressure parameters were evaluated. Concerning the in vitro investigation, the vasorelaxant effect of AGAPE was tested in isolated thoracic aortic rings. Results: AGAPE extract significantly decreased the blood pressure parameters in hypertensive rats. Moreover, the results revealed that AGAPE exhibited antihypertensive effect through its vasorelaxant properties. More interestingly, this vasorelaxant activity seems to be probably mediated through activation of K+ ATP-sensitive (KATP) channels. Conclusion: The study demonstrates the antihypertensive activity of aqueous Asteriscus graveolens extract in hypertensive rats through activation of vascular KATP channels. This finding supports the use of this plant for the management of hypertension in Morocco.

Cardiovascular Effects of Micromeria graeca (L.) Benth. ex Rchb in Normotensive and Hypertensive Rats

2020 ◽  
Vol 20 (8) ◽  
pp. 1253-1261
Author(s):  
Mourad Akdad ◽  
Mohamed Eddouks
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Arterial Blood Pressure ◽  
Antihypertensive Activity ◽  
Computer Assisted ◽  
Hypertensive Rats ◽  
Vasorelaxant Effect ◽  
Arterial Blood

Aims: The present study was performed in order to analyze the antihypertensive activity of Micromeria graeca (L.) Benth. ex Rchb. Background: Micromeria graeca (L.) Benth. ex Rchb is an aromatic and medicinal plant belonging to the Lamiaceae family. This herb is used to treat various pathologies such as cardiovascular disorders. Meanwhile, its pharmacological effects on the cardiovascular system have not been studied. Objective: The present study aimed to evaluate the effect of aqueous extract of aerial parts of Micromeria graeca (AEMG) on the cardiovascular system in normotensive and hypertensive rats. Methods: In this study, the cardiovascular effect of AEMG was evaluated using in vivo and in vitro investigations. In order to assess the acute effect of AEMG on the cardiovascular system, anesthetized L-NAME-hypertensive and normotensive rats received AEMG (100 mg/kg) orally and arterial blood pressure parameters were monitored during six hours. In the sub-chronic study, rats were orally treated for one week, followed by blood pressure assessment during one week of treatment. Blood pressure was measured using a tail-cuff and a computer-assisted monitoring device. In the second experiment, isolated rat aortic ring pre-contracted with Epinephrine (EP) or KCl was used to assess the vasorelaxant effect of AEMG. Results: Oral administration of AEMG (100 mg/kg) provoked a decrease of arterial blood pressure parameters in hypertensive rats. In addition, AEMG induced a vasorelaxant effect in thoracic aortic rings pre-contracted with EP (10 μM) or KCl (80 mM). This effect was attenuated in the presence of propranolol and methylene blue. While in the presence of glibenclamide, L-NAME, nifedipine or Indomethacin, the vasorelaxant effect was not affected. Conclusion: This study showed that Micromeria graeca possesses a potent antihypertensive effect and relaxes the vascular smooth muscle through β-adrenergic and cGMP pathways.

scholarly journals Aqueous Extract of Matricaria pubescens Exhibits Antihypertensive Activity in L-NAME-induced Hypertensive Rats through its Vasorelaxant Effect

2019 ◽  
Vol 17 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Ayoub Amssayef ◽  
Mohamed Eddouks
Keyword(s):  
Aqueous Extract ◽  
North Africa ◽  
Antihypertensive Activity ◽  
Hypertensive Rats ◽  
Vasorelaxant Effect ◽  
Aerial Parts ◽  
Arterial Blood ◽  
Vasodilator Activity ◽  
Beneficial Action ◽  
Vasorelaxant Activity

Background: Matricaria pubescens is a medicinal plant from North Africa. This plant is widely used in alternative medicine as a remedy against rheumatism, inflammation, diabetes and hypertension. Aim: The aim of the study was to evaluate the possible antihypertensive and vasodilator activity of the aqueous extract of Matricaria pubescens (M. pubescens). Material and Methods: In the current study, the aqueous extract of the aerial parts of M. pubescens (AEMP) was prepared and its antihypertensive activity was examined in N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Results: The results indicated that AEMP reduced the systolic, diastolic, mean arterial blood pressure in hypertensive rats but not in normotensive rats. The data revealed that AEMP exhibits its antihypertensive effect through vasorelaxant activity. More interestingly, this study approved that the vasorelaxant capacity of AEMP seems to be mediated through vascular cyclooxygenase pathway, the opening of K+ channels and sGC-cGMP induction pathway. Conclusion: The study illustrates the beneficial action of M. pubescens as an antihypertensive agent.

scholarly journals Quantified Piper sarmentosum Roxb. Leaves Aqueous Leaf Extract and Its Antihypertensive Effect in Dexamethasone-Induced Hypertensive Rats

2021 ◽  
Vol 50 (1) ◽  
pp. 171-179
Author(s):  
Muhammad Firdaus Azmi ◽  
Amilia Aminuddin ◽  
Jamia Azdina Jamal ◽  
Adila A Hamid ◽  
Azizah Ugusman
Keyword(s):  
Blood Pressure ◽  
Heavy Metal ◽  
Antioxidant Activity ◽  
Aqueous Extract ◽  
Antihypertensive Effect ◽  
Underlying Mechanism ◽  
Antihypertensive Activity ◽  
Hypertensive Rats ◽  
Chromatography Method ◽  
Herbal Products

The quality control of raw herbal materials is important to ensure the safety, efficacy, and reproducibility of herbal products. Herbal products with consistent efficacy should be standardized and quantified based on their bioactive phytochemical compounds. Piper sarmentosum Roxb. has been reported for its antihypertensive activity. However, its antihypertensive effect on dexamethasone-induced hypertension still lacks information. In this study, the quality of two batches of raw P. sarmentosum leaf materials was assessed for heavy metal and microbial contents, and their aqueous extracts were assayed for antioxidant activity. The aqueous extract of the second batch of P. sarmentosum leaves was the only extract that passed the heavy metal and microbial limits and had the highest antioxidant activity (50.00 ± 2.88%); therefore, this extract was used for subsequent studies. The extract was quantified for two phytochemical markers, rutin (0.09 ± 0.002%) and vitexin (0.23 ± 0.007%), using a validated ultrahigh performance liquid chromatography method. The quantified extract (500 mg/kg/day orally) was able to lower the systolic blood pressure, diastolic blood pressure, and mean arterial pressure of dexamethasone-induced hypertensive rats comparable to the positive control drug, captopril. In summary, the quantified aqueous extract of P. sarmentosum based on rutin and vitexin lowers the blood pressure of dexamethasone-induced hypertensive rats, but its underlying mechanism warrants further investigation.

Measurement of hemodynamic parameters and antidepressant activity in hypertensive rats following two weeks consumption of Acacia tortilis leaves extract

2021 ◽  
Vol 11 ◽  
Author(s):  
Abdulhalim Serafi ◽  
Aisha Azmat ◽  
Muhammad Ahmed ◽  
Mohammed Bafail ◽  
Zahir Hussain
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Salt Intake ◽  
Forced Swim Test ◽  
Antidepressant Activity ◽  
Antihypertensive Activity ◽  
Acacia Tortilis ◽  
Dietary Salt ◽  
Hypertensive Rats ◽  
Arterial Blood

Background: Depression is common in hypertensive patients, and monotherapy may contribute for controlling depression in hypertensive patients and improving the socioeconomic outcomes. Previous studies have shown that Acacia tortilis possesses hypotensive activity. Objectives: Hence, the present study was planned to evaluate the hemodynamic activity and antidepressant effects of an ethanolic extract of Acacia tortilis leaves (ATEL) in salt-induced hypertensive rats. Methods: Sprague-Dawley rats were divided into 5 groups for experiments. The rats received respective treatment for 15 days: G1: Control (C); G2: Hypertensive control (HC: high dietary salt, 4% 10ml/kg); G3-5: HC+ ATEL (50, 100, 150mg/kg respectively). Cardiac hemodynamics (mean arterial blood pressure: MAP and heart rate: HR) were measured in the anaesthetized rats by an invasive method. For this method, one carotid artery was catheterized, a pressure catheter (pressure volume Millar microtip catheter connected to the Mikro-Tip Pressure-Volume System from Ultra Foundation Systems, PowerLab) was inserted, and the blood pressure (MAP in mm Hg) and HR (beats/min) were monitored continuously during the experiment. For the neuropharmacological studies, antidepressant activity was assessed by forced swim test on the 15th day. Results: A dose-dependent significant increase in mobility time was observed in rats (G3-5) treated with HC + different doses of ATEL (p < 0.05). However, the mobility time was significantly reduced by HC (G2) treatment compared with that of the control (p< 0.05). The hypertensive control (high dietary salt: HC) group showed significant increases in SP, DP, MAP, and HR (p<0.05) compared to the control (G1) group. At all doses (50, 100 and 150 mg/kg), MAP and HR were found to decrease significantly (p<0.05) when compared with the values in the HC (G2) group. Further analysis revealed an improvement in heart rate variability (HRV) in ATEL-treated hypertensive rats. Conclusion: The present research suggests that increased dietary salt intake not only increases blood pressure significantly but also increases depression. ATEL contains some efficacious constituents, N, N-dimethyltryptamine (DMT: a 5-HT1A agonist) with predominant antidepressant and antihypertensive activity. Hence, ATEL appears to be a valuable plant extract that can be useful, at least as an adjunct, for therapy in patients who suffer from both depression and hypertension. Objectives: Hence, the present study was planned to evaluate the hemodynamic activity and antidepressant effects of an ethanolic extract of Acacia tortilis leaves (ATEL) in salt-induced hypertensive rats. Methods: Sprague-Dawley rats were divided into 5 groups for experiments. The rats received respective treatment for 15 days: G1: Control (C); G2: Hypertensive control (HC: high dietary salt, 4% 10ml/kg); G3-5: HC+ ATEL (50, 100, 150mg/kg respectively). Cardiac hemodynamics (mean arterial blood pressure: MAP and heart rate: HR) were measured in the anaesthetized rats by an invasive method. For this method, one carotid artery was catheterized, a pressure catheter (pressure volume Millar microtip catheter connected to the Mikro-Tip Pressure-Volume System from Ultra Foundation Systems, PowerLab) was inserted, and the blood pressure (MAP in mm Hg) and HR (beats/min) were monitored continuously during the experiment. For the neuropharmacological studies, antidepressant activity was assessed by forced swim test on the 15th day. Results: A dose-dependent significant increase in mobility time was observed in rats (G3-5) treated with HC + different doses of ATEL (p < 0.05). However, the mobility time was significantly reduced by HC (G2) treatment compared with that of the control (p< 0.05). The hypertensive control (high dietary salt: HC) group showed significant increases in SP, DP, MAP, and HR (p<0.05) compared to the control (G1) group. At all doses (50, 100 and 150 mg/kg), MAP and HR were found to decrease significantly (p<0.05) when compared with the values in the HC (G2) group. Further analysis revealed an improvement in heart rate variability (HRV) in ATEL-treated hypertensive rats. Conclusion: The present research suggests that increased dietary salt intake not only increases blood pressure significantly but also increases depression. ATEL contains some efficacious constituents, N, N-dimethyltryptamine (DMT: a 5-HT1A agonist) with predominant antidepressant and antihypertensive activity. Hence, ATEL appears to be a valuable plant extract that can be useful, at least as an adjunct, for therapy in patients who suffer from both depression and hypertension.

Study of Antihypertensive Activity of Anvillea radiata in L-Name-Induced Hypertensive Rats and HPLC-ESI-MS Analysis

2020 ◽  
Vol 20 (7) ◽  
pp. 1059-1072
Author(s):  
Mourad Akdad ◽  
Mohammed Ajebli ◽  
Andrea Breuer ◽  
Farid Khallouki ◽  
Robert W. Owen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Administration ◽  
Antihypertensive Activity ◽  
Hypertensive Rats ◽  
Esi Ms ◽  
Vasorelaxant Effect ◽  
Aerial Parts ◽  
Arterial Blood ◽  
Ms Analysis ◽  
Ca2 Channels

Objective: This study aimed to evaluate the effect of the aqueous extract of Anvillea radiate (A. radiata) aerial parts (AEAR) on arterial blood pressure in normotensive and hypertensive rats. Methods: The effect of the acute and sub-chronic administration of AEAR on the following blood pressure parameters: systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) was evaluated in normotensive and L-NAME induced hypertensive rats. In the second experiment, the vasorelaxant effect of AEAR was assessed in isolated aortic rings from rats with functional endothelium pre-contracted with epinephrine (EP) or KCl, and six antagonists/ inhibitors were used to explore the mechanisms of action involved in the vasorelaxant effect. In order to determine the phytochemical contents of Anvillea radiata, HPLC-ESI-MS analysis was conducted. Results: Daily oral administration of AEAR (100 mg/kg) provoked a significant decrease in SBP, MBP, and DBP without affecting HR in hypertensive rats. In addition, AEAR (0.08-0.64 mg/ml) revealed a vasorelaxant effect in thoracic aortic rings pre-contracted by EP (10 μM) or KCl (80 mM). This effect was reduced in the presence of Nifedipine, L-Name or Methylene blue. The polyphenolic compounds of AEAR were determined. Conclusion: This study revealed that AEAR possesses a potent antihypertensive activity and its vasorelaxant activity seems to be mediated through Ca2+ channels, direct nitric oxide (NO), and NO/cGMP pathways. Chlorogenic acid and caffeic acid identified in A. radiata could be at least partially responsible for the antihypertensive activity of this extract.

scholarly journals Antihypertensive Activity of Eucommia Ulmoides Oliv: Male Flower Extract in Spontaneously Hypertensive Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Zhen-Jiang Ding ◽  
Chao Liang ◽  
Xiao Wang ◽  
Xin Yao ◽  
Ruo-Han Yang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Aqueous Extract ◽  
Spontaneously Hypertensive Rats ◽  
Male Flower ◽  
Antihypertensive Activity ◽  
Eucommia Ulmoides ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Male Flowers

Eucommia ulmoides Oliv. is a traditional medical plant in Asia; however, it is still unknown whether Eucommia male flowers have an antihypertensive activity. In this study, we found that the aqueous extract of Eucommia ulmoides Oliv. male flowers can lower the blood pressure of SHR in a dose-dependent manner. Mechanistic studies suggested that the aqueous extract of male flowers can promote the mRNA and protein expressions of ACE2 in the kidney of SHR. ELISA assay showed that the plasma levels of ANG II was decreased, while ANG-(1–7) was increased in SHR treated with the aqueous extract of male flowers. ACE2 inhibitor DX600 can reverse the aqueous extract of Eucommia ulmoides Oliv. male flower-induced downregulation of Ang II and upregulation of Ang-(1–7), as well as the reduction of blood pressure in SHR. Moreover, Ang-(1–7)-Mas receptor antagonist A-779 abolished the antihypertensive effects of the aqueous extract of Eucommia ulmoides Oliv. male flower in SHR. The aqueous extract of Eucommia ulmoides Oliv. male flowers exhibited an antihypertensive action through the activation of ACE2-Ang-(1–7)-Mas signaling pathways in spontaneously hypertensive rats.

scholarly journals Cissus quadrangularis Aqueous Extract Attenuates Angiotensin II-Induced Hypertension In Urethane-Anesthetized Rats

2021 ◽  
Vol 14 (4) ◽  
pp. 1459-1462
Author(s):  
Faiyaz Ahmed
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Aqueous Extract ◽  
Antihypertensive Activity ◽  
Intravenous Route ◽  
Ang Ii ◽  
Arterial Blood ◽  
Cissus Quadrangularis ◽  
Induced Hypertension

Hypertension is a major cardiovascular problem resulting in significant mortality. Cissus quadrangularis having several pharmacological effects has not been evaluated for its ability to modulate blood pressure. Thus, the ability of C. quadrangularis aqueous extract (CQE) to modulate blood pressure was evaluated in normotensive and angiotensin II-induced hypertensive rats under urethane anesthesia. The animals were divided into four groups namely, control (saline injection), CQE (extract alone, 10 mg/kg), Ang II (Ang II alone, 0.5 µg/kg) and Ang II + CQE (Ang II + extract). All treatments were delivered by intravenous route and in Ang II + CQE group, Ang II was injected 30 min after injection of the extract. Hemodynamic parameters, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), and heart rate (HR) were recorded by the BIOPAC system after the cannulation of the carotid artery and jugular vein. The results indicated that CQE lowered SBP, DBP, MABP and heart rate to varying degrees in normotensive rats compared to control groups. In case of angiotensin II-induced hypertension, CQE administration resulted in substantial decrease in SBP, DBP, and MABP which were raised by Ang II. CQE reduced SBP, DBP, and MABP by 12, 59, and 11%, respectively. It is worth noting that, while SBP was not brought down to baseline levels by CQE, DBP was, suggesting significant hypotensive/antihypertensive activity of CQE. Further research is required to determine the molecular mechanism of C. quadrangularis extract’s hypotensive/antihypertensive action and to conduct clinical trials to establish its optimal use as an antihypertensive therapeutic.

Effects of hydralazine on blood pressure, pressor mechanisms, and cardiac hypertrophy in two-kidney, one-clip hypertensive rats

1986 ◽  
Vol 64 (12) ◽  
pp. 1528-1534 ◽  
Author(s):  
James Tsoporis ◽  
Frans H. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Time Course ◽  
Antihypertensive Effect ◽  
Plasma Catecholamines ◽  
Left Ventricular ◽  
Prolonged Treatment ◽  
Internal Diameter ◽  
Hypertensive Rats ◽  
Blood Volumes

In 2-kidney, 1-clip hypertensive rats, the time course of changes in blood pressure (BP), heart rate, activity of the sympathetic nervous system and the renin–angiotensin system, plasma and blood volumes, left ventricular (LV) and right ventricular (RV) weight, and LV dimensions were evaluated during treatment with hydralazine 80 and 120 mg/L drinking water for 2 days or 1, 2, 3, 5, and 8 weeks. Hydralazine induced initially a clear antihypertensive effect (mean BP from 170–180 down to 135–145 mmHg (1 mmHg = 133.32 Pa)), subsequently tolerance developed. Heart rate, plasma catecholamines, and the blood pressure response to hexamethonium were not affected by treatment. Significant increases in plasma renin activity occurred during the initial 1–3 weeks of treatment. Plasma and blood volumes showed only small increases with prolonged treatment. RV weight and LV internal diameter showed significant increases at 3, 5, and 8 weeks of treatment, LV weight at 5 and 8 weeks. LV wall thickness did not change significantly. Thus, treatment with the arterial vasodilator hydralazine causes both RV hypertrophy and eccentric LV hypertrophy. Intravascular volume expansion, associated possibly with redistribution of blood volume to the central compartment, may play a major role in these cardiac effects. Increased renin release but not a generalized increase in sympathetic tone may play a role in the development of tolerance to the antihypertensive effect.

scholarly journals Antihypertensive Effect ofSyzygium cuminiin Spontaneously Hypertensive Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Rachel Melo Ribeiro ◽  
Vicente Férrer Pinheiro Neto ◽  
Kllysmann Santos Ribeiro ◽  
Denilson Amorim Vieira ◽  
Iracelle Carvalho Abreu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Vascular Reactivity ◽  
Antihypertensive Effect ◽  
Maximum Effect ◽  
Syzygium Cumini ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

This study evaluated thein vivopotential antihypertensive effect of hydroalcoholic extract ofSyzygium cuminileaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as itsin vitroeffect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01–4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (Emax⁡) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated thatSyzygium cuminireduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.

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