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ORIGINAL ARTICLE
Year : 2015  |  Volume : 18  |  Issue : 6  |  Page : 762-770

Effect of Hibiscus sabdariffaon blood pressure and electrolyte profile of mild to moderate hypertensive Nigerians: A comparative study with hydrochlorothiazide


1 Department of Physiology, College of Medicine, University of , Enugu Campus, Enugu, Nigeria
2 Department of Medicine, Enugu State University Teaching Hospital, Parklane, Enugu, Nigeria
3 Department of Ophthalmology,University of Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria
4 Department of Physiology, School of Basic Medical Sciences,University of Benin, Benin City, Edo State, Nigeria
5 Department of Physiology, College of Medicine, University of , Enugu Campus,Parklane, Enugu, Nigeria

Date of Acceptance27-Feb-2015
Date of Web Publication20-Aug-2015

Correspondence Address:
D C Nwachukwu
Department of Physiology, College of Medicine, University of , Enugu Campus, Enugu
Nigeria
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Source of Support: Nil., Conflict of Interest: None


DOI: 10.4103/1119-3077.163278

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   Abstract 

Background: Hibiscus sabdariffa (HS) is widely consumed in Nigeria as a refreshing beverage and also as an antihypertensive agent. Since three decades ago when its antihypertensive activities were reported in several animal experiments, its consumption has greatly increased. Aim: The aim of this study is to investigate the effect of HS consumption on blood pressure (BP) and electrolytes of mild to moderate hypertensive Nigerians and compare it with that of hydrochlorothiazide (HCTZ), a diuretic widely used asfirst-line antihypertensive drug. Subjects and Methods: Eighty newly diagnosed, but untreated mild to moderate hypertensive subjects attending Medical Out-Patients clinic of Enugu State University Teaching Hospital, Enugu, were recruited for the study. They were randomly divided into three groups: A, B and C. Those in Groups A were given placebo; those in Group B took HCTZ while those in Group C were given HS. Treatment lasted for 4 weeks. BP, serum, and urine electrolytes were measured at baseline, weekly during treatment and 1 week after withdrawal of treatment. Results: At the end of treatment, both HCTZ and HS significantly (P < 0.001) reduced systolic BP, diastolic BP, mean arterial pressure and serum Na+ compared to placebo. When compared to each other, HCTZ significantly (P < 0.001) reduced serum Na+ and Cl− compared to HS and significantly (P < 0.001) increased K+ and Cl− output in urine. After withdrawal of treatment, the fall in BP and serum Na+ in HS group were significant compared to HCTZ where they returned to baseline values. No side effect was reported during the study. Conclusion: HS was a more effective antihypertensive agent than HCTZ in mild to moderate hypertensive Nigerians and did not cause electrolyte imbalance. HS showed longer duration of action compared to HCTZ and reduction in serum Na+ may be another antihypertensive mechanism of action of HS.

Keywords: Clinical trial, essential hypertension and electrolytes, Hibiscussabdariffa,hydrochlorothiazide


How to cite this article:
Nwachukwu D C, Aneke E, Nwachukwu N Z, Obika L, Nwagha U I, Eze A A. Effect of Hibiscus sabdariffaon blood pressure and electrolyte profile of mild to moderate hypertensive Nigerians: A comparative study with hydrochlorothiazide. Niger J Clin Pract 2015;18:762-70

How to cite this URL:
Nwachukwu D C, Aneke E, Nwachukwu N Z, Obika L, Nwagha U I, Eze A A. Effect of Hibiscus sabdariffaon blood pressure and electrolyte profile of mild to moderate hypertensive Nigerians: A comparative study with hydrochlorothiazide. Niger J Clin Pract [serial online] 2015 [cited 2019 Nov 18];18:762-70. Available from: http://www.njcponline.com/text.asp?2015/18/6/762/163278




   Introduction Top


Hypertension is the most common cardiovascular disease in Nigeria (Ajayi and Akintomide, 1995)[1] and is a major cause of morbidity and mortality worldwide (Catanzaro and Kurtz, 2002).[2] Approximately 20% of the world's adults are estimated to have hypertension. It is responsible for over 7.1 million deaths annually (Cooper et al., 1997).[3] Hypertension is more severe and associated with more severe sequelae in blacks when compared with white patients (Whittle et al., 1991; Rayner and Becker, 2006).[4],[5] Nigerians are particularly susceptible to hypertension and its complications such as disabling and fatal strokes remain a major cause of morbidity and mortality (Nwosu et al., 1992;[6] Iman and Olorunfemi, 2002; Akinkugbe, 2003).[7][8][9] Etiologically, hypertension is regarded as a multi-factorial disease condition in which a myriad of physiological mechanisms participate to elevate and maintain blood pressure (BP) (Kaplan, 1994; Beevers et al., 2001).[10],[11]

The role of electrolytes in the pathogenesis and maintenance of essential hypertension has received considerable attention, debate and study (Blaustein et al., 1991; Kuller, 1997; Milan et al., 2002).[12][13][14] These studies have implicated Na+, K+, Cl− in both Caucasians and blacks with their values being higher in black hypertensives (Aderounmu and Salako, 1979; Worthington et al., 1993)[15],[16] and have also shown that intracellular and plasma (or serum) Na+ and Cl− concentration are significantly higher in hypertensives than normotensives. Human and animal models of hypertension have shown that Na+ and Cl− must act in concert to induce BP rise (Whitescarver et al., 1986).[17] In various human population, K+ is an important predictor of mean arterial pressure (MAP); hypertensives have been reported to have lower plasma (or serum) and total body K+ as well as lower urinary K+ excretion levels than normotensives (Kurtz et al., 1987; Morton and Abraham, 1987; Krishna et al., 1989).[18][19][20]

In spite of the many hypotheses that have been advanced in respect of the possible mechanisms for essential hypertension, it is not clear whether the kidney provides the causative factors or bears the brunt of the vascular disease (Coleman et al., 1981).[21] Kidney regulates electrolyte balance in the body and diseases that adversely affect this balance may lead to hypertension (Blaustein et al., 1991; Beevers et al., 2001; Vikrant and Tiwari, 2001).[11],[12],[22] Electrolyte imbalance has been reported among Nigerians with essential hypertension (Iyalomhe et al., 2008)[23] and this may be responsible for the susceptibility of Nigerians to hypertension and its complications (Ukoh and Obasohan, 1992).[24]

Several animal studies (Obiefuna et al., 1994; Adegunloye et al., 1996; Mojiminiyi et al., 2000)[25][26][27] and human studies (Jonadet et al., 1990; Herrera–Arellano et al., 2004; McKay et al., 2010)[28][29][30] have reported the antihypertensive activities of Hibiscus sabdariffa (HS). These studies have suggested several mechanisms of action such as vasodilatory effect, inhibition of Ca2+ influx, inhibition of ACE among others. None of these studies have examined the effect of HS on electrolyte balance and its clinical implication. Electrolyte imbalance has been implicated in the pathogenesis of hypertension and the speculation that HS has antihypertensive effect has greatly increased its consumption both at home and social gatherings in Nigeria by hypertensives and nonhypertensives alike (Onyenekwe et al., 1999).[31] This study is designed to investigate the effect of HS on BP and electrolyte profile of mild to moderate hypertensive Nigerians and compare it with that of hydrochlorothiazide (HCTZ), a diuretic widely used in the treatment of hypertension, with a view to determining its therapeutic usefulness.


   Subjects and Methods Top


Study setting

Enugu is located in the South-East Zone of Nigeria. It is the capital of Enugu State in Nigeria. It is a cosmopolitan city and used to be the regional capital of Eastern Nigeria. It has an estimated population of over one million people, and most of the inhabitants are predominantly civil servants, traders, and artisans. The study lasted for 5 weeks.

Human subjects

Sample size

This was determined using the formula below:



Zα = 1.96 for 5% level of significance

Z1-β = 0.84 at 80% statistical power

r = n1/n2 = 1 for equal sample size

σ = common standard deviation

d = difference between mean values in previous study (Herrera-Arellano et al., 2004).[29]

Eighty mild to moderate hypertensive subjects (aged 31–70 years) attending Medical Out-Patient clinic of Enugu State University Teaching Hospital, Parklane, Enugu, were recruited for the study, but only 75 completed it. Five subjects withdrew for nonmedical reasons. The study was carried out in line with the guidelines of the Helsinki Declaration for human studies (as amended) and approved by the Institutional Ethical Committee (EC: ESUTTH/EC/11002).

Inclusion criteria

  • Newly diagnosed but untreated mild to moderate hypertension using WHO/ISH (2003) classification [Table 1]
  • The subjects were adequately briefed about the study and oral consent obtained.
Table 1: WHO/ISH (2003) classification of hypertension

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Exclusion criteria

  • Patients with diabetes, nephropathy, cardiopathy, hepatic disease and cancer were excluded from this study
  • Pregnant women, individuals with evidence of secondary hypertension, chronic smokers and alcoholics were excluded
  • Those who did not complete the study were also excluded.


All participants were prohibited from participating in other clinical studies throughout the duration of the study.

Block randomization was used to divide subjects who met the inclusion criteria into three Groups (A, B and C) using Quickcalcs (GraphPad Software, Armonk, NY: IBM Corp). The group they belong to and the type of treatment given were concealed from the subjects as well as the physicians that took the measurements.

Group A

Subjects were given equivalent dose (150 mg/kg) in volume of placebo taken orally before breakfast daily for 4 weeks.

Group B

Subjects were given 25 mg HCTZ (Esidrex®, Novarvatis, Switzerland) orally once daily before breakfast for 4 weeks.

Group C

Subjects were given HS infusion (150 mg/kg) orally once daily before breakfast for 4 weeks.

All the subjects were given weekly appointments and a week worth of infusion/medication.

Blood pressure, serum and urine electrolytes were measured at baseline, weekly during treatment for 4 weeks and 1-week after withdrawal of treatment. Clinical evaluation and treatment adherence were evaluated weekly via oral submission by subjects and close relatives and by inspection of plastic containers given to them.

Plant collection

Dried calyces of HS were purchased from Ogbete Main Market, Enugu. They were authenticated by Mr. A. Ozioko of the herbarium section of Botany Department, University of Nigeria, Nsukka and a specimen voucher number UNH/314b was assigned to it for future reference.

Preparation of Hibiscus sabdariffainfusion

The method of Herrara-Arellano et al. (2004)[29] was used with two modifications.

20 g of dry calyces were weighed and ground in an electric mill to obtain particles < 2 mm. It was used to make an infusion by adding 1 L of boiling clean bottle water (Aquafina, Pepsi Nig. Ltd.) and allowed to stand for 30 min.

The solution was filtered using Whatman's No. 1 filter paper. The filtrates were stored in clean plastic containers at room temperature.

The following two modifications were made:

  • Infusions were prepared and given to patients
  • Time allowed for extraction was extended from 10 to 30 min.


Placebo preparation

Blackcurrant (Glaxosmithkline®, UK) was used as placebo. It was diluted with clean bottle water (Aquafina, Pepsi Nig. Ltd.) to obtain approximately the same color as HS infusion. Blackcurrant was chosen among other drinks because it has a similar color as the locally prepared "Zobo" drink and preliminary investigation using 20 healthy subjects who were given equivalent dose of it for 2 weeks showed no effect on BP.

Hibiscus sabdariffadosage calculation

Daily dose = 150mg/kg

1kg = 150mg

Weight of Patient = W kg

W kg = 150×W mg = 0.15×W g

From extraction,

20g = 1l

Thus,

0.15×W g = (0.15×W/20×1)l = (0.007×W)l

150 mg/kg was chosen because it produced approximately the same color as the locally brewed HS ("Zobo") drink and is far below the LD50 of HS (>5000 mg/kg).

Hibiscus sabdariffaextract standardization

The HS extract was standardized using the colorimeter method of Fuleki and Francis (1968).[32] This method was based on the ability of anthocyanin (the active component of HS) to produce a color at pH 1.0 that disappears at pH 4.5. This special characteristic is produced by a pH dependent structural transformation of the chromophore. The colored oxonium ion predominates at pH 1.0, while the noncolor hemiketal is presented at pH 4.5. This method ensures accurate and fast determination of total anthocyanins, in spite of the presence of polymeric pigments and other compounds. This procedure was done with 1 ml of the HS solution (20 g of dried HS calyx extracted with 1 L of water). Two samples were gauged to 5 ml solution at pH 1.0 and 4.5, respectively. These solutions were filtered through a 0.45 mm membrane (Gelman acrodisk) and analyzed with a spectrophotometer at 510 and 700 nm, respectively. The total anthocyanins concentration is obtained using the formula:

Concentration (mg/ml) = A × MW × FD × 1000/(ɛ × 1).

(A = Absorbance of diluted sample; MW = Molecular weight of anthocyanin; FD = Dilution factor; ɛ = Molar absorptivity)

From this method, the total anthocyanin contained in 20 g of HS dissolved in 1 L was 10.04 mg.

Measurements

Blood pressure measurement

Sitting BP was measured using Accoson® mercury sphygmomanometer. Systolic BP (SBP) was taken asfirst appearance of Korotkov sounds and the diastolic BP (DBP) the point of disappearance of the sounds (Phase V). Two consecutive readings were taken from each subject at 5 min interval and the average of these was taken as the mean blood pressure reading. Measurement was taken between 8.00 am and 10.00 am. Any constrictive clothing on the arm was removed before measurement was taken.

Measurement of serum electrolytes

Venous blood (5 ml) was withdrawn from medial cubital vein into a vacutainer and allowed to stand undisturbed for 25 min. The clot formed was removed by centrifuging at 2000 rpm for 10 min. The resulting supernatant (serum) was transferred to a clean polypropylene tube using Pasteur pipette. Serum electrolytes (Na+, K+ and Cl) were determined by ion selective electrode using Audicom automated electrolyte analyzer (AC9000 series) China.

Measurement of urine electrolytes

Urine samples were collected and Na+, K+ and Cl were measured with an ion-selective electrode analyzer; Audicom automated Electrolyte analyzer (AC9000 Series), China.

Statistical analysis

Results were presented as mean ± standard error of mean data was classified by groups and weeks of treatment and analyzed using SPSS Version 20 by IBM Corp. One-way analysis of variance was used to compare differences between groups, and further analysis was carried out using Bonferroni test. P ≤ 0.05 was considered significant.


   Results Top


Blood pressure changes

At the end of treatment (week 4), SBP decreased by 12.9 ± 4.31 mmHg and 17.08 ± 5.12 mmHg in HCTZ and HS group respectively; similarly, DBP decreased by 9.50 ± 2.06 mmHg and 11.12 ± 3.12 mmHg respectively. The percentage decline in SBP in HCTZ group was 8.55 ± 1.64% while that of HS was 11.38 ± 2.53%. DBP decreased by 9.59 ± 1.60% and 12.13 ± 2.48 in HCTZ and HS groups respectively [Table 2]. These changes were significant (P < 0.001) in both treatment groups when compared with of placebo. MAP followed a similar pattern with HS group recording a higher percentage decrease of 11.74 ± 2.12% than HCTZ where 9.14 ± 1.62% decrease was obtained [Table 2]. 1-week after withdrawal of treatment, the fall in SBP, DBP and MAP in HS group were still significant (P < 0.001) compared to those of placebo while BP returned to baseline levels in HCTZ group.
Table 2: Clinical characteristics of subjects

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When compared to HCTZ, there was significant difference in the reduction in SBP (P < 0.01), DBP (P < 0.01) and MAP (P < 0.01) in HS group at week 5 [Figure 1]-[Figure 3].
Figure 1: Systolic blood pressure measurements following the administration ofplacebo (control), hydrochlorothiazide andHibiscus sabdariffa on mild to moderate hypertensive subjects. Each point on the graph represents the average of atleast 25 independent measurements. Error bars are SEM; *P< 0.05, **P< 0.01, ***P< 0.001, ⊠P< 0.05, ⊠P< 0.01 (two way ANOVA with Bonferroni posttest, using Graphpad prism 5.0). Inset is a comparison of thetreatment groups

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Figure 2: Diastolic blood pressure measurements following the administrationofplacebo (control), hydrochlorothiazide andHibiscus sabdariffaon mild to moderatehypertensive subjects. Each point on the graphrepresents the averageof at least 25 independent measurements. Error bars are SEM; ***P< 0.001,⊠⊠P< 0.01, ⊠⊠⊠P< 0.001, ⊠⊠P< 0.01(two way ANOVA with Bonferroni posttest, using Graphpad prism 5.0). Inset is a comparison of the treatment groups

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Figure 3: Mean arterial blood pressure measurements following the administration of placebo (control), hydrochlorothiazide and Hibiscus sabdariffa on mild to moderate hypertensive subjects. Each point on the graph represents the average of at least 25 independent measurements. Error bars are SEM; ***P< 0.001, ⊠⊠P< 0.01, ⊠⊠⊠P< 0.001, ⊠⊠P< 0.01 (two way ANOVA with Bonferroni posttest, using Graphpad prism 5.0)

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Serum and urine electrolytes

Both HCTZ and HS reduced serum Na+ and their effect were significant (P < 0.001) compared to that of placebo; HCTZ also reduced serum Na+ significantly (P < 0.01) compared to HS at weeks 3–5 [Figure 4]. Both HCTZ and HS produced significant decrease (P < 0.01) in serum K+ and Cl− at the end of treatment when compared to placebo [Figure 5] and [Figure 6]. HCTZ produced the highest percentage change of −12.83% ± 0.48%, −14.71% ± 1.825% and −15.80% ± 0.65% in serum Na+, K+ and Cl− respectively. At the end of treatment, HS produced a change of −10.36% ±0.32% in serum Na+ which was significant (P < 0.001) compared to placebo but not to HCTZ. 1-week after withdrawal of treatment, the change in serum Na+ produced by HS (−6.71% ± 0.31%) was still significant (P < 0.001) compared to placebo but serum electrolytes returned to their baseline levels in HCTZ group.
Figure 4: Serum Na+ concentration measurements following the administration of placebo (control), hydrochlorothiazide and Hibiscus sabdariffa on mild to moderate hypertensive subjects. Each point onthe graph represents the average of at least 25 independent measurements. Error bars are SEM, ***P< 0.001, ⊠⊠⊠P< 0.001, ⊠P< 0.05, ⊠⊠⊠P< 0.001 (two way ANOVA with Bonferroni posttest, using Graphpad prism 5.0). Inset is a comparison of the treatment groups

Click here to view
Figure 5: Serum K+ concentration measurements following the administration ofplacebo (control), hydrochlorothiazide andHibiscus sabdariffa on mild to moderate hypertensive subjects. Each point on the graph represents the average of at least 25 independent measurements. Error bars are SEM; ***P< 0.001, ⊠⊠⊠P< 0.001, ⊠P< 0.05 (two way ANOVA with Bonferroni posttest, using Graphpad prism 5.0). Inset is acomparison of the treatment groups

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Figure 6: Serum Cl- concentration measurements following the administration ofplacebo (control), hydrochlorothiazide andHibiscus sabdariffa onmild to moderate hypertensive subjects. Each point on the graph represents the average of at least 25 independent measurements. Error bars are SEM; *P< 0.05, ***P' 0.001, ⊠P< 0.05, ⊠⊠⊠P< 0.001, ⊠⊠⊠P< 0.001 (two way ANOVAwith Bonferroni posttest, using Graphpad prism 5.0). Inset is a comparisonof the treatment groups

Click here to view


When compared to HS, HCTZ significantly (P < 0.001) reduced serum K+ at the end of treatment but produced opposite effect on serum Cl [Figure 6].

At the end of treatment, urinary output of Na+ increased significantly only in HCTZ at weeks 3 (P < 0.01) and 4 (P < 0.001) group whereas HS did not produce any significant change in urine Na+ compared to placebo [Figure 7]. Both HCTZ and HS did not produce any significant change in urine Cl. When compared to each other, changes in urine Na+ produced by HCTZ and HS treatments were not significant but that on urine K+ was opposite and significant (P < 0.001); HCTZ increased K+ but HS reduced it [Figure 8]. HCTZ increased urine Cl while HS reduced it; both effects were significant at week 4 (P < 0.01) compared to placebo [Figure 7]; when the effects of both active treatments were compared to each other, they were significant (P < 0.001) throughout the duration of study [Figure 1] [Figure 2] [Figure 3] [Figure 4] [Figure 5] [Figure 6] [Figure 7] [Figure 8] [Figure 9].
Figure 7: Urine Na+ concentration measurements following the administration of placebo (control), hydrochlorothiazide andHibiscus sabdariffa on mild to moderate hypertensive subjects. Each point on the graph represents the average ofat least 25 independent measurements. Errorbars are SEM; **P< 0.01, ⊠⊠P< 0.01, ⊠⊠⊠P< 0.001, ⊠P< 0.05 (two way ANOVA with Bonferroni posttest, using Graphpad prism 5.0). Inset is a comparison of the treatment groups

Click here to view
Figure 8: Urine K+ concentration measurements following the administration of placebo (control), hydrochlorothiazide andHibiscus sabdariffa on mild to moderate hypertensive subjects. Each point onthe graph represents the average of at least 25 independent measurements. Error bars are SEM; **P< 0.01, ***P' 0.001, ⊠⊠P' 0.01, ⊠⊠⊠P< 0.001, ⊠⊠⊠P< 0.001 (two way ANOVA with Bonferroni posttest, using Graphpad prism 5.0). Inset is a comparison of the treatment groups

Click here to view
Figure 9: Urine Cl- concentration measurements following the administration ofplacebo (control), hydrochlorothiazide andHibiscus sabdariffa on mild to moderate hypertensive subjects. Each point on the graph represents the average of at least 25 independentmeasurements. Error bars are SEM; **P< 0.01, ***P< 0.001, ⊠P< 0.05, ⊠⊠P< 0.01, ⊠P< 0.05, ⊠⊠⊠P' 0.001 (two way ANOVA with Bonferroni posttest, using Graphpad prism 5.0). Inset is a comparison of the treatment groups

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   Discussion Top


The consumption of botanicals as complimentary/alternative medicine has been encouraged because they are relatively cheap and coupled with the fact that they could significantly contribute to the improvement of human health in terms of cure and prevention of various human disorders in addition to the less frequent side effects reported when compared to modern medicine (Hou et al., 2005).[33] In the present study, HS demonstrated a significant BP lowering effect that was higher than that of HCTZ in mild to moderate hypertensive subjects. SBP, DBP and MAP were significantly (P < 0.001) reduced compared to placebo in both groups. About 76% therapeutic effectiveness was achieved in the HS group compared to 60% in HCTZ group. Therapeutic effectiveness is a direct measure of therapeutic success that is, those whose BP was reduced to < 140 mmHg (SBP) and < 90 mmHg (DBP). Thus, HS exhibited greater antihypertensive effect than HCTZ. This result agrees with the previous report by Herrera–Arellano et al. (2004)[29] which showed HS producing a therapeutic effectiveness of 78.95% in Mexicans. The higher therapeutic effectiveness obtained in the HS treated group may be due to multiple mechanisms of antihypertensive action by HS in contrast to HCTZ which is a thiazide diuretic whose mechanism of action is inhibition of Na+-Cl− symport at the distal convoluted tubule, thereby, depleting the body Na+.

Results from several studies suggest that aqueous extract of HS achieved its antihypertensive activity by at least four specific mechanisms: Diuretic (Onyenekwe et al., 1999; Mojiminiyi et al., 2000);[27],[31] vasodilatation (Obiefuna et al., 1994; Adegunloye et al., 1996),[25],[26] Inhibition of Ca2+ influx (Ajay et al., 2007)[34] and ACE inhibition (Jonadet et al., 1990; Herrarre–Arellano et al., 2004).[28],[29] Another possible antihypertensive mechanism of action of HS is by blockage of AT1 receptors which has been reported in other plant species that has anthocyanins (Caballera-George et al., 2002).[35] ACE inhibition and AT1 receptor blocking were due to the action of anthocyanins present in HS which was also demonstrated in the present study. The vasorelaxant effect of HS are mediated through cholinergic and/or histaminergic mechanisms produced by membrane stabilization and stimulation of vascular Na+-K+ ATPase activity and inhibition of Ca2+ release from intracellular stores (Adegunloye et al., 1996)[26] and may also be mediated by endothelium-dependent and independent mechanisms (Obiefuna et al., 1994).[25] The endothelium-dependent vasodilator effect was due to activation of endothelium-derived nitric oxide/cGMP-relaxant pathway (Ajay et al., 2007)[34] and that the endothelium-independent effect was possibly due to inhibition of Ca2+ influx by the action of quercetin and eugenol present in the HS (Salah et al., 2002).[36]

In the present study, HS caused 11.38% and 12.13% decrease in SBP and DBP respectively compared to HCTZ which decreased SBP and DBP by 8.55% and 9.59% respectively. This suggests that apart from diuretic effect via ACE inhibition and AT1receptor blocking, that HS possesses other mechanisms of antihypertensive action as earlier stated. These results agree with those from previous study by Haji-Faraji and Haji-Tarkhani (1999)[37] where HS was reported to produce a decrease of 11% in both SBD and DBP.

The role of serum Na+ in the pathogenesis and maintenance of essential hypertension has been reported in previous studies (Morton and Abraham, 1987; Ukoh and Obasohan, 1992).[19],[24] Serum Na+ was positively associated with BP (Shailendra et al., 2011)[38] thus; agents that lower serum Na+ may have antihypertensive action. Modest dietary salt restriction employed as a definitive or adjunctive treatment of hypertension has been shown to reduce BP or permitted drug treatment to be substantially reduced or discontinued (Alderman et al., 1993; Melander et al., 2007).[39],[40] Serum Na+ was significantly reduced in both HCTZ and HS groups with the reduction in HS group being sustained even after withdrawal of treatment. The prolonged reduction in serum Na+ observed in HS group correlated with fall in BP which underscores the role of Na+ in the pathogenesis of hypertension and suggests that HS has a longer duration of action compared to HCTZ. Thus, similar to HCTZ, reduction in serum Na+ may be another significant antihypertensive mechanism of action of HS especially in a population like ours where people habitually consume salt. Unlike HS, a significant reduction in serum K+ and Cl− was observed in HCTZ group, suggesting that its treatment may cause electrolyte imbalance.

Both HCTZ and HS caused natriuresis, but HCTZ significantly increased K+ loss in the urine whereas HS reduced K+ excretion, which suggests that it may be a K+ sparing diuretic. The result of the present study agrees with that of Herrera–Arellano et al. (2004)[29] who observed a natriuretic effect in hypertensive Mexicans treated with aqueous calyx extract of HS but contradicted that of Mojiminiyi et al. (2000)[27] who reported Na+ retention in HS treated rats. This difference could be because these workers used animals, consumption of HS was not regulated (ad libitum) and the concentration of HS solution was higher in their study. High doses of HS have been shown to affect the structure (Jaiyesimi et al., 2002)[41] and functions (Orisakwe et al., 2004; Aguwa et al., 2004)[42],[43] of the kidney. The relative electrolyte stability in the HS group suggests that it has a comparative advantage over HCTZ as an antihypertensive agent.


   Conclusion Top


The results of this study showed that HS was a more effective antihypertensive agent than HCTZ in mild to moderate hypertensive Nigerians. Higher therapeutic effectiveness and longer duration of action were observed in the HS group. In addition to other reported antihypertensive mechanisms of action of HS, reduction in serum Na+ may be an additional mechanism of action. Unlike HCTZ, HS did not cause electrolyte imbalance and thus demonstrated a comparative advantage over HCTZ. This study also validated the ethno medicinal use of HS as an antihypertensive agent in Nigeria. In spite of the observed antihypertensive effectiveness of HS, the involvement of appropriate government regulatory agencies such as National Agency for Food, Drug Administration and control in regulation of HS consumption is strongly recommended in order to avoid its abuse.

Limitations of the study

  • Inability to quantify anthocyanins using high-performance liquid chromatography that is a more sensitive and accurate method due to unavailability of the equipment in our institution
  • Reliance on subjects and close relatives for treatment adherence.


 
   References Top

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Aderounmu AF, Salako LA. Plasma and erythrocyte cations and permeability of the erythrocyte membrane to cations in essential hypertension. Afr J Med Med Sci 1979;8:45-9.  Back to cited text no. 2
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
 
 
    Tables

  [Table 1], [Table 2]


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