scholarly journals ANTIHYPERTENSIVE EFFECT OF THE PUNICA GRANATUM JUICE IN DEOXYCORTICOSTERONE ACETATE–SALT MODEL OF HYPERTENSION IN RATS

Author(s):  
Chaudhari Pankaj M ◽  
Baviskar Dheeraj T ◽  
Mahajan Sachin N

 Objective: Hypertension an important global health challenge is the prevalent cause of cardiovascular disease. Natural products are emerging as new therapeutic tools in the management of hypertension due to side effects and the patient’s adherence of the existing treatments. In the present study, we investigated the antihypertensive effect of the Punica granatum juice in deoxycorticosterone acetate (DOCA)–salt model of hypertension in rats.Methods: Antihypertensive activity was evaluated in P. granatum juice extract (PGJ) (PJ-100 mg/kg and 300 mg/kg; p.o.) for 4 weeks in DOCA treated rats. Blood pressure by non-invasive (indirect) method and invasive method was measured. Further, vascular reactivity to noradrenaline (1 μg/kg), adrenaline (1 μg/kg), phenylephrine (1 μg/kg), serotonin (1 μg/kg), and angiotensin II (25 ng/kg) was recorded. Antioxidant studies such as thiobarbituric acid reactive substances (TBARS); while enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) in kidney tissue was also carried out.Results: Administration of PGJ (PJ-100 mg/kg and 300 mg/kg; p.o.) for 4 weeks in DOCA treated rats significantly (p<0.05) reduced the mean arterial blood pressure and vascular reactivity changes to various catecholamines. PJ treatment significantly (p<0.05) decreased the levels of TBARS; while enzyme activity of SOD, CAT, and GSH in kidney tissue was significantly increased.Conclusion: Results of the present work suggest that PGJ has an antihypertensive action in unilateral nephrectomized DOCA-salt hypertensive rats and could be possible starting point for treatment of hypertension with increased patient adherence.

1975 ◽  
Vol 48 (2) ◽  
pp. 147-151
Author(s):  
C. S. Sweet ◽  
M. Mandradjieff

1. Renal hypertensive dogs were treated with hydrochlorothiazide (8−2 μmol/kg or 33 μmol/kg daily for 7 days), or timolol (4.6 μmol/kg daily for 4 days), a potent β-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period. 2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide. 3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered. 4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic.


1980 ◽  
Vol 48 (2) ◽  
pp. 308-312 ◽  
Author(s):  
P. J. Leuenberger ◽  
S. A. Stalcup ◽  
L. M. Greenbaum ◽  
R. B. Mellins ◽  
G. M. Turino

To determine if angiotension converting enzyme activity is altered by acute pathophysiological insults, we assessed angiotensin I conversion using a blood pressure response technique in anesthetized dogs studied during acute 100% O2 breathing and acute acid-base derangements. Also, we determined systemic vascular reactivity to angiotensin II by measuring the magnitude and duration of the arterial blood pressure response to intra-arterial injections of angiotensin II under these same conditions. Angiotensin I conversion found in normoxia [91 +/- 7 (SD)%] was unchanged by acute acidosis, alkalosis, and hyperoxia. During acute hyperoxia the mean half time of the hypertensive response increased from 68 +/- 25 (SD) s at a PaO2 of 112 +/- 18 (SD) Torr to 100 +/- 34 (SD) s at a PaO2 of 491 +/- 47 (SD) Torr (P less than 0.01). No other pathophysiological condition studied had any effect on reactivity of systemic vasculature to angiotensin II. We conclude that, except during acute hypoxia as previously shown, converting enzyme activity is resistant to other pathophysiological insults and that vascular responsiveness to angiotensin II is enhanced by hyperoxia.


Author(s):  
El-Ouady Fadwa ◽  
Mohamed Eddouks

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.


2020 ◽  
Vol 20 (8) ◽  
pp. 1253-1261
Author(s):  
Mourad Akdad ◽  
Mohamed Eddouks

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.


Author(s):  
Mohammed Ajebli ◽  
Mohamed Eddouks

Aims and objective: The aim of the study was to investigate the effect of aqueous aerial part extract of Mentha pulegium L. (Pennyrile) (MPAE) on arterial pressure parameters in rats. Background: Mentha pulegium is a medicinal plant used to treat hypertension in Morocco. Material and methods: In the current study, MPAE was prepared and its antihypertensive activity was pharmacologically investigated. L-NAME-hypertensive and normotensive rats have received orally MPAE (180 and 300 mg/kg) during six hours for the acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. While, in the in vitro experiment, isolated denuded and intact thoracic aortic rings were suspended in a tissue bath system and the tension changes were recorded. Results: A fall in blood pressure was observed in L-NAME-induced hypertensive treated with MPAE. The extract also produced a dose-dependent relaxation of aorta pre-contracted with NE and KCl. The study showed that the vasorelaxant ability of MPAE seems to be exerted through the blockage of extracellular Ca2+ entry. Conclusion: The results demonstrate that the extract of pennyrile exhibits antihypertensive activity. In addition, the effect may be, at least in part, due to dilation of blood vessels via blockage of Ca2+ channels.


1979 ◽  
Vol 57 (s5) ◽  
pp. 387s-389s ◽  
Author(s):  
J. S. Floras ◽  
P. Fox ◽  
M. O. Hassan ◽  
J. V. Jones ◽  
P. Sleight ◽  
...  

1. Twenty-four hour intra-arterial blood pressure measurements and electrocardiograms were obtained from 12 subjects with untreated essential hypertension. 2. The patients kept records of their activity, paying particular attention to times of retiring to bed, and times of waking in the morning. 3. All subjects were treated with a single daily dose of atenolol (50 to 200 mg) for between 2 and 9 months, and then underwent a second 24 h blood pressure study. 4. Arterial blood pressure was lowered significantly throughout the 24 h period with a single daily dose of atenolol.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Mohammad Alshuniaber ◽  
Omar Alhaj ◽  
Qasem Abdallah ◽  
Haitham Jahrami

Purpose This study aims to investigate the antihypertensive effect of camel milk hydrolysate in rats with fructose-induced hypertension. Design/methodology/approach The antihypertensive effect of fermented camel milk was determined using 6 groups comprising 36 Wistar male rats. Blood pressure of rats was altered via exposure to a 10% fructose (w/v) diet in drinking water for 3 weeks before conducting 21 days of treatment. The authors conducted the experiment for short and long term using different doses of 800 and 1,200 mg/kg body weight. Serum was used to assay total cholesterol (TC), triglyceride (TG), glucose and insulin levels using standard biochemical kits. Findings The group that received 1,200 mg hydrolysate camel milk (HM) has significantly (p = 0.003) reduced systolic and diastolic blood pressure after a short exposure time (4–8 h). These effects were significantly (p = 0.005) comparable to the nifedipine (NIF) drug group. Similar long-term (21 days) effects on blood pressure were observed in 1,200 mg HM and NIF groups. Angiotensin-converting enzyme (ACE) activity and levels were also reduced in a correlation with blood pressure reduction only in HM1200 and HM800 treated groups. The authors observed no significant effect on blood pressure in groups receiving the 800 mg HM or 1,200 mg unhydrolyzed camel milk (UM). Rats receiving the 10% fructose diet showed significant differences from control rats regarding their blood biochemistry, including TG, TC, blood glucose and insulin levels. Rats in groups NIF, HM1200 and HM800 showed a significant (p < 0.05) reduction in serum glucose, insulin, TG and TC levels toward the baseline level. Research limitations/implications Further mechanistic investigation on the HM antihypertensive activity is highly recommended before suggesting HM as a product to reduce blood pressure. While drug–food interaction between HM and antihypertensive drugs, especially ACE inhibitors, is probable, UM seems not to affect blood pressure or ACE activity and therefore is expected to have no or minimal effects on the activity of other antihypertensive drugs. Investigation of ACE expression from various organs including lungs and leukocytes is highly recommended in future works using sodium dodecyl-sulfate polyacrylamide gel electrophoresis and western blot analysis or reverse transcription polymerase chain reaction. Originality/value No previous studies have measured the antihypertensive activity of milk hydrolysate mediated by the reduction of ACE activity and levels in plasma. Mechanisms involved in attenuating the levels of ACE warrant further investigation.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Lodi C Roksnoer ◽  
Joep H van Esch ◽  
Richard van Veghel ◽  
Ingrid M Garrelds ◽  
Usha M Bhaggoe ◽  
...  

Objective: Neprilysin inhibitors (NEPi) prevent the breakdown of natriuretic peptides, promoting vasodilation and natriuresis. However, they also increase angiotensin and endothelin-1 (ET1). This study compared the combination of an AT1 receptor antagonist (irbesartan, IRB) ± a low or a high dose of the NEPi thiorphan in renin-overexpressing, hypertensive TGR(mREN2)27 rats. Methods: TGR(mREN2)27 rats were treated for three weeks with vehicle, IRB (15 mg/kg.day) or IRB + thiorphan (0.1 or 1.0 mg/kg.day; TH0.1 and TH1.0). Hemodynamics were evaluated by telemetry, and vascular reactivity was determined in isolated mesenteric arteries (Mulvany myograph). Results: Baseline mean arterial blood pressure (MAP) was 168±3 mmHg. All treatments lowered MAP by ≈50 mmHg around day 4. After 7 days, MAP started to increase during treatment with IRB or IRB+TH1.0 (to 141±10 mmHg and 133±10 mmHg, respectively, on day 21), while MAP in rats treated with IRB+TH0.1 remained low at 104±5 mmHg on day 21. Heart weight/body weight ratio, cardiac ANP expression and myocyte size decreased only in the IRB+TH0.1 group. Plasma ET1 was increased only by TH1.0 versus IRB alone, and this increase was accompanied by an increase in renal sodium-hydrogen exchanger 3 (NHE3) protein expression: ET1-induced constriction was reduced by IRB+TH0.1 only. Vascular ET B R expression levels and studies with the ET1 type B receptor (ET B R) antagonist BQ788 revealed that this reduction was most likely due to ET B R upregulation. Conclusion: TH0.1 enhanced the blood pressure-lowering effects of irbesartan and diminished cardiac hypertrophy. Higher doses of thiorphan resulted in significant ET1 rises and renal NHE3 upregulation, thereby increasing blood pressure and sodium reabsorption. The simultaneously occurring upregulation of vasodilatory ET B R was insufficient to overcome this effect. Clearly therefore, too much NEPi on top of AT1 receptor antagonism might be harmful.


2020 ◽  
Vol 21 (21) ◽  
pp. 8349
Author(s):  
Ivona Kosovic ◽  
Natalija Filipovic ◽  
Benjamin Benzon ◽  
Ivana Bocina ◽  
Merica Glavina Durdov ◽  
...  

Our study analyzed the expression pattern of different connexins (Cxs) and renin positive cells in the juxtaglomerular apparatus (JGA) of developing, postnatal healthy human kidneys and in nephrotic syndrome of the Finnish type (CNF), by using double immunofluorescence, electron microscopy and statistical measuring. The JGA contained several cell types connected by Cxs, and consisting of macula densa, extraglomerular mesangium (EM) and juxtaglomerular cells (JC), which release renin involved in renin-angiotensin- aldosteron system (RAS) of arterial blood pressure control. During JGA development, strong Cx40 expression gradually decreased, while expression of Cx37, Cx43 and Cx45 increased, postnatally showing more equalized expression patterning. In parallel, initially dispersed renin cells localized to JGA, and greatly increased expression in postnatal kidneys. In CNF kidneys, increased levels of Cx43, Cx37 and Cx45 co-localized with accumulations of renin cells in JGA. Additionally, they reappeared in extraglomerular mesangial cells, indicating association between return to embryonic Cxs patterning and pathologically changed kidney tissue. Based on the described Cxs and renin expression patterning, we suggest involvement of Cx40 primarily in the formation of JGA in developing kidneys, while Cx37, Cx43 and Cx45 might participate in JGA signal transfer important for postnatal maintenance of kidney function and blood pressure control.


1998 ◽  
Vol 275 (5) ◽  
pp. H1826-H1833 ◽  
Author(s):  
L. G. Melo ◽  
A. T. Veress ◽  
U. Ackermann ◽  
H. Sonnenberg

Atrial natriuretic peptide (ANP) exerts a chronic hypotensive effect due to a decrease in total peripheral resistance (TPR). This study examines if chronic ANP-dependent vasodilation is attributable to differences in the cardiovascular regulatory activity of vascular endothelium (VE), based on evidence that ANP affects synthesis/release and target cardiovascular effects of endothelin-1 (ET-1), C-type natriuretic peptide (CNP), and nitric oxide (NO). To determine if the synthetic activity of resistance vasculature VE is chronically altered by plasma ANP activity, we measured ET-1, CNP, and endothelial constitutive NO synthase (ecNOS) concentration and total NOS enzyme activity in homogenates of kidney, heart, lung, hindquarter skeletal muscle, and brain from hypotensive transgenic mice with elevated plasma ANP, hypertensive knockout mice (−/−) characterized by the absence of ANP, and the corresponding normotensive wild-type (NT, +/+) mice. Tissue distribution and abundance patterns of ET-1, CNP, ecNOS, and NOS enzyme activity were comparable between the different genotypes and did not differ significantly between mutant and control mice. Antagonism of ETA/B receptors in −/− and +/+ mice in vivo with SB-209670 reduced arterial blood pressure (ABP) significantly and comparably in both genotypes (−27 ± 4 and −25 ± 2% change for −/− and +/+ mice, respectively) independent of any significant changes in heart rate (HR) (−6 ± 8 and −4 ± 4% change for −/− and +/+ mice, respectively). Immunoneutralization of CNP-specific guanylate cyclase-linked receptors (GC-B) with monoclonal antibodies (3G12) increased ABP slightly, but not significantly, by similar relative amounts in both −/− (10 ± 6% change) and +/+ mice (8 ± 3% change), without changing HR significantly (4 ± 1% change for both +/+ and −/− mice). Inhibition of NOS activity (by N G-nitro-l-arginine methyl ester) significantly increased ABP, but the changes were comparable between −/− (53 ± 5% change) and +/+ mice (50 ± 6% change) and occurred in the absence of significant changes in HR (−1 ± 5 and 7 ± 5% change for −/− and +/+ mice, respectively). We conclude that the differences in ABP associated with chronic variations in endogenous ANP activity are not due to alterations in synthesis or responsiveness of the cardiovascular system to the effects of ET-1, CNP, or NO.


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