Hypertension is a major public health problem that adversely affects the health status of individuals, families and communities. L-arginine levels of a total of 90 consecutively-recruited hypertensive subjects and 50 age-matched non-hypertensive controls were studied. Plasma from subjects and control participants were analyzed for L-arginine. The mean values of L-arginine level were significantly lower among the hypertensive subjects which are (174.33 ± 78.31 μmol/L) compared to those of the 50 non-hypertensive controls (237.82 ± 261.16 μmol/L) (p = 0.04). There was no statistically significant difference in the L-arginine levels of hypertensive subjects based on gender, age and ethnici-ty (p = 0.87, 0.23 and 0.57) respectively. The L-arginine level was significantly higher among married hypertensive subjects (181.71 ± 78.17 μmol/L) compared to single or unmarried subjects (130.62 ± 65.99 μmol/L) (p = 0.03). The mean value of L-arginine level was significantly higher among hypertensive subjects with mild blood pressure (187.63 ± 77.93 μmol/L) compared to those with high blood pressure (156.93 ± 76.31 μmol/L). The difference however was not statistically significant (p = 0.05). The findings from this study confirm that the level of L-arginine is lower among hypertensive subjects compared to non-hypertensive controls. Age, gender and ethnicity did not have a significant effect on the L-arginine levels of hypertensive subjects. L-arginine level was significantly lower among single hypertensive patients and those with markedly raised blood pressure. It is recommended the L-arginine supplement be prescribed to hypertensive patient as a prophylactic measure. There is a need to enlighten hypertensive patients in the area on the need to maintain a balanced diet containing sufficient level of L-arginine.
Hypertension (HTN or HT), also known as high blood pressure or arterial hypertension, is a chronic medical condition in which the blood pressure in the arteries is elevated. Blood pressure is expressed by two measurements, the systolic and diastolic pressures, which are the maximum and minimum pressures, respectively, in the arterial system. The systolic pressure occurs when the left ventricle is most contracted; the diastolic pressure occurs when the left ventricle is most relaxed prior to the next contraction. Normal blood pressure at rest is within the range of 100 - 140 mmHg systolic and 60 - 90 mmHg diastolic. Hypertension is present if the blood pressure is persistently at or above 140/90 millimeters mercury (mmHg) for most adults. In most people with established essential hypertension, increased resistance to blood flow (total peripheral resistance) accounts for the high pressure while cardiac output remains normal. Some individuals develop the typical features of established essential hypertension in later life as their cardiac output falls and peripheral resistance rises with age. The increased peripheral resistance in established hypertension is mainly attributable to structural narrowing of small arteries and arterioles although a reduction in the number or density of capillaries may also contribute. Hypertension is also associated with decreased peripheral venous compliance which may increase venous return, increase cardiac preload and, ultimately, cause diastolic dysfunction. It is defined as a transitory or sustained elevation of systemic arterial blood pressure to induce cardiovascular damage or other adverse consequences. This has become a chronic condition and a major public health problem that adversely affects health status of individuals, families and communities [
The prevalence of hypertension has been found to be 44% in Western Europe and 28% in North America [
The endogenous source of NO in the body has been shown to be due to the secondary effect of L-arginine metabolism by a family of enzymes known as NO synthases (NOSs). These enzymes utilize the substrates L-arginine, molecular oxygen, and NADPH to produce L-citrulline and NO. The arginine/NOS/NO pathway appears to be very important in regulating vascular tone and remodelling in systemic hypertension. Changes in NOS expression and increased NO generation are generally interpreted to be a protective compensatory response to the underlying disease processes that increase pulmonary vascular resistance. Decreases in NO bioavailability contribute to the development of hypertension. The vasodilatory properties of NO are well characterized and are clearly important in the setting of systemic hypertension [
L-arginine is an amino acid that is necessary for the body to make protein and is found in red meat, poultry, fish, and dairy foods. L-arginine has been shown to reduce pulmonary vascular resistance in humans with hypertension [
The study was conducted in the Department of Medicine Specialist Hospital Sokoto and samples were analyzed in the Department of Haematology and Blood Transfusion Science in the Faculty of Medical Laboratory Science of Usmanu Danfodio University Sokoto (UDUS). The Department and the collaborating Specialist Hospital Sokoto have enabling environment (human and material endowment) to carry out this study. Sokoto State is located in the extreme North Western part of Nigeria, near to the confluence of the Sokoto River and the Rima River. With an annual average temperature of 28.3˚C (82.9˚F), Sokoto is, on the whole, a very hot area. However, maximum daytime temperatures are for most of the year is generally under 40˚C (104.0˚F). The warmest months are February to April when daytime temperatures can exceed 45˚C (113.0˚F). The rainy season is from June to October during which showers are a daily occurrence. There are two major seasons, wet and dry which are distinct. Report from the 2007 National Population Commission indicated that the state had a population of 3.6 million [
The study population comprised of hypertensive patients men and women attending the general outpatient clinic of Specialist Hospital Sokoto and non-hy- pertensive healthy men and women recruited from among student, staff of Usmanu Danfodiyo University Sokoto (UDUS) and Specialist Hospital Sokoto, Nigeria.
This case-control study involved 140 consecutively-recruited participants made up of 90 hypertensive patients (subjects) presenting to the Department of Medicine of Specialist Hospital, Sokoto, Nigeria and 50 healthy, age and gender matched non-hypertensive individuals (controls) recruited from among staff of Usmanu Danfodiyo University Sokoto (UDUS) and Specialist Hospital Sokoto, Nigeria. Fifty controls were included due to cost constraints with the reagent.
The study included all consenting, consecutively recruited legal adults (≥18 years) and confirmed hypertensive patients (by a qualified physician) attending Medical Clinic in Specialist Hospital Sokoto.
The following persons who did not meet the inclusion criteria; non-adult (<18 years), non-hypertensive patients and non-consenting hypertensive patients were excluded from participating in this study.
The data collected was recorded on an Excel spread sheet and later subjected to statistical analysis using statistical software (SPSS Version 20.0). Results were expressed as a mean and standard deviation. Differences in values based on socio-demographic variables of subjects was determined and compared statistically. A p-value of ≤0.05 was considered as significant in all statistical comparisons.
Ethical clearance was obtained from the ethical committee of Specialist Hospital Sokoto. The study was carried out in accordance with the Code of Ethics for Biomedical Research involving human subjects.
Written informed consent was obtained from all hypertensive patients and non-hypertensive individuals participating in the study. Socio-demographic information (age, gender, marital status and ethnicity) was collected using a questionnaire.
Three (3 ml) millilitres of whole blood will be collected from each subject into an EDTA anticoagulated tubes. The specimens were centrifuged to separate the plasma from the red cells. The plasma sample was used for plasma L-arginine estimation. L-arginine testing was carried out using the Immunodiagnostic AG (Germany) ELISA plasma L-arginine kits. This assay is based on the method of competitive enzyme linked immunoassays. The sample preparation includes the addition of a derivatization reagent for L-arginine derivatization. Afterwards, the treated samples and the polyclonal L-arginine antiserum was incubated in wells of a microtiter plate coated with an L-arginine-derivative (tracer). During the incubation period, the target L-arginine in the sample competes with the tracer immobilized on the wall of the microtiter wells for the binding of the polyclonal antibodies. The L-arginine in the sample displaces the antibodies out of the binding to the tracer. Therefore, the concentration of the tracer bound antibody is inverse proportional to the L-arginine concentration in the sample. During the second incubation step, a peroxidase-conjugated antibody was added to each microtiter well to detect the anti-L-arginine antibodies. After washing away the unbound components tetramethylbenzidine (TMB) was added as a peroxidase substrate. Finally, the enzymatic reaction is terminated by an acidic stop solution. The color changes from blue to yellow, and the absorbance is measured in a photometer at 450 nm. The intensity of the yellow colour is inversely proportional to the L-arginine concentration in the sample. This means that high L-arginine concentration in the sample reduces the concentration of tracer- bound antibodies and lowers the photometric signal. A dose response curve of absorbance unit (optical density, OD at 450 nm) versus concentration was generated using the values obtained from the standards. L-arginine present in the patient samples was determined directly from this curve.
Subjects for this case control study included 90 consecutively-recruited hypertensive patients aged 20 - 89 years with mean age 43.76 ± 14.04.
Parameter | Hypertensive Subjects and Non-Hypertensive Controls | t-value | p-value | |
---|---|---|---|---|
Subjects Mean ± SD N = 90 | Controls Mean ± SD N = 50 | |||
L-arginine (µmol/L) | 174.33 ± 78.31 | 237.82 ± 261.16 | −2.11 | 0.04 |
Parameter | Gender | t-value | p-value | |
---|---|---|---|---|
Male Mean ± SD N = 62 | Female Mean ± SD N = 28 | |||
L-arginine (µmol/L) | 176.58 ± 84.53 | 173.31 ± 84.53 | −160 | 0.87 |
Parameter | Age | t-value | p-value | |
---|---|---|---|---|
20 - 39 Years Mean ± SD N = 47 | 40 - 89 Years Mean ± SD N = 43 | |||
L-arginine (µmol/L) | 164.83 ± 79.70 | 184.71 ± 76.32 | −1.23 | 0.23 |
Parameter | Marital Status | t-value | p-value | |
---|---|---|---|---|
Married Mean ± SD N = 77 | Single Mean ± SD N = 13 | |||
L-arginine (µmol/L) | 181.71 ± 78.17 | 130.62 ± 65.99 | 2.23 | 0.03 |
hypertensive subjects was investigated. The L-arginine level was significantly higher among married hypertensive subjects (181.71 ± 78.17 µmol/L) compared to single or unmarried subjects (130.62 ± 65.99 µmol/L) (p = 0.03).
Hypertension has become a chronic condition and a major public health problem that adversely affects health status of individuals, families and communities. Worldwide hypertension is estimated to cause 7.1 million premature deaths and 4.5% of the disease burden. The population of global disease burden attributable to hypertension is substantial.
This study investigated the level of L-arginine among hypertensive subjects and non-hypertensive controls. The result obtained from this study showed that the mean L-arginine level was significantly lower (p = 0.04) among the hypertensive subjects compared to the non-hypertensive controls. Our finding is consistent with a previous report which indicated that L-arginine levels are reduced in Pre-eclampsia (PE), a syndrome of pregnancy-induced hypertension [
This study also considered effect of gender on the L-arginine level among hypertensive subjects. The L-arginine level was marginally higher among males compared to female hypertensive subjects (p = 0.87). The reason for lower level of L-arginine observed among female hypertensive subjects is not known. It is not known whether menstrual cycle, pregnancy, hormones and lactation may
Parameter | Ethnic Group | t-value | p-value | |
---|---|---|---|---|
Hausa Mean ± SD N = 67 | Fulani Mean ± SD N = 23 | |||
L-arginine (µmol/L) | 177.12 ± 79.73 | 166.21 ± 75.11 | 0.57 | 0.57 |
Parameter | Blood Pressure Level | t-value | p-value | |
---|---|---|---|---|
High BP Mean ± SD N = 39 | Mild BP Mean ± SD N = 51 | |||
L-arginine (µmol/L) | 156.93 ± 76.31 | 187.63 ± 77.93 | −1.93 | 0.05 |
play a role. However, the incidence of uncontrolled hypertension has been shown to be greater in men than in women [
Our study also investigated the effect of age on the L-arginine level among hypertensive patient subjects. The L-arginine was marginally higher among older subjects (40 - 82 years) compared to younger hypertensive subjects (20 - 39 years) (p = 0.23). The reason for this age-related difference in the L-arginine and nitric oxide among hypertensive subjects is unknown. Socioeconomic status, psychosocial stressors/risks, and other environmental factors may play a role. Previous report shows that aging in rats is associated with a reduction in NO substrate (L-arginine) and excretion of NO metabolites [
The effect of marital status on the L-arginine of hypertensive was investigated. The L-arginine level was significantly higher (p = 0.03) among married hypertensive subjects compared to those who were single. The reason for this marital status-related difference is not known. Less psychosocial distress and better access to dietary sources of L-arginine including meat, fish, soy, beans, lentils, whole grains and nuts among married hypertensive subjects may be responsible [
The L-arginine level of hypertensive subjects were compared based on ethnicity. The L-arginine was marginally higher among the Hausa ethnic group compared to the Fulani ethnic group (p = 0.57). Our finding of an ethnic variation in the level of L-arginine among hypertensive subjects of African descent in Sokoto is consistent with previous report which indicated that the L-arginine is affected by psychosocial distress with higher susceptibility in Black Africans. This interaction may contribute to the higher cardiovascular disease risk in Black Africans [
Hypertension, also known as high blood pressure or arterial hypertension, is a chronic medical condition in which the blood pressure in the arteries is elevated. Blood pressure is expressed by two measurements, the systolic and diastolic pressures, which are the maximum and minimum pressures, respectively, in the arterial system. The systolic pressure occurs when the left ventricle is most contracted; the diastolic pressure occurs when the left ventricle is most relaxed prior to the next contraction. Normal blood pressure at rest is within the range of 100 - 140 mmHg systolic and 60 - 90 mmHg diastolic. Hypertension is present if the blood pressure is persistently at or above 140/90 millimeters mercury (mmHg) for most adults; different criteria apply to children [
Arginine is involved in several important physiological processes, many of which impact vascular function. Arginine deficiency or lack of availability, and changes in arginine metabolism, has the potential to contribute to increased blood pressure and endothelial cell dysfunction. The question often arises―is arginine supplementation effective in preventing or treating hypertension, and if so, what is the mechanism? Potential role of L-arginine supplementation as a new effective strategy of improving endothelial function in patients with hypertension is recently under consideration. Previous report indicates that L-arginine supplementation increases plasma arginine, citrulline and TAS in patients with mild arterial hypertension. Augmented concentrations of L-arginine stimulate NO biosynthesis which leads to reduction of oxidative stress [
In conclusion, the findings in this study confirmed that the level of L-arginine and Nitric Oxide is lower among hypertensive patient compared to non-hyper- tensive controls. The level L-arginine was lower among unmarried hypertensive patients compared to married hypertensive patients and among hypertensive patients with markedly raised blood pressure compared to those with mildly raised blood pressure level.
We recommend that a further research study should be conducted involving a larger population of hypertensive patient to determine the level of and L-argi- nine. We also recommend that L-arginine supplements be prescribed routinely to hypertensive patient as a prophylaxic measure. There is need for public enlightenment programme to educate hypertensive patients on the need to maintain a balanced diet containing sufficient amount of L-arginine containing food. It is recommended that facilities for the routine monitoring of L-arginine among hypertensive in the area be provided.
Erhabor, O., Ibrahim, A.B., Abdulrahaman, Y., Chiroma, A.H., Imoru, M., Udomah, F.P., Ahmed, M., Ibrahin, K., Buhari, H., Okwesili, A., Onuigwe, O., Liman, H.M., Van Dyke, K., Egenti, N.B. and Iwueke, I.P. (2017) L- Arginine Levels among Hypertensive Patients in Sokoto, North Western Nigeria. Open Journal of Blood Diseases, 7, 1-15. http://dx.doi.org/10.4236/ojbd.2017.71001