Aims
There is a high prevalence of hypertension in the African population and it is known that
vascular dysfunction (including nitric oxide (NO) bio-availability markers) play an important
role in the development of cardiovascular diseases. Since very little is known regarding the
role of markers of NO bio-availability in Africans, the aim of this study was to compare
markers of NO bio-availability (namely L-arginine, L-citrulline, asymmetric dimethylarginine
(ADMA) and symmetric dimethylarginine (SDMA)), ambulatory blood pressure (BP) and
markers of end organ damage between African and Caucasian school teachers. Additionally,
we also aimed to determine whether these markers of NO bio-availability are associated with
ambulatory BP and markers of end organ damage in both ethnic groups.
Methods
The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study was a
cross-sectional study, including urbanised African (N=181) and Caucasian (N=209) men and
women, between the ages of 25 and 65 years. Cardiovascular measurements included
ambulatory blood pressure, pulse wave velocity (PWV), electrocardiographic Cornell product
and carotid intima media thickness (cIMT). Anthropometric measurements included height,
weight and waist circumference.
Various bio-markers were analysed, including glucose, L-arginine, ADMA, SDMA, Lcitrulline,
reactive oxygen species, albumin-to-creatinine ratio (ACR) and estimated
creatinine clearance (eCCR).
Characteristics of groups were compared with independent T-tests and Chi-square tests.
Single and partial analyses were used to investigate associations between NO bioavailability
markers with ambulatory BP measurements and markers of end organ damage.
Analyses of covariance (ANCOVA) were used for comparison of variables between groups
to determine significant differences, while adjusting for age, body mass index and antihypertensive
medication. Forward stepwise multiple regression analyses were performed to
determine if independent associations exist between ambulatory BP measurements or
markers of end organ damage with either- L-arginine, L-citrulline, ADMA or SDMA as the
main independent variable.
Results and conclusion
The Africans and Caucasians were of similar ages. However, the Africans had higher blood
pressure therefore their cardiovascular profile was unfavourable compared to that of the
Caucasians.
The inhibitors of NO biosynthesis, ADMA and SDMA, were significantly lower in the Africans
(p=0.046; p<0.001, respectively). However, the NO bio-availability markers, L-arginine and
L-citrulline, were higher in the African compared to the Caucasian participants (all p values
<0.05) regarded as significant.
When performing unadjusted analyses, we found significant negative associations between
eCCR and L-citrulline in all four subgroups: African men (r=-0.27; p=0.013), African women
(r=-0.24; p=0.021), Caucasian men (r=-0.21; p=0.044) and Caucasian women (r=-0.28;
p=0.003). The association of eCCR with L-citrulline was confirmed to be independent of
confounders in all groups: African men (R2=0.46; β=-0.23; p=0.006), African women
(R2=0.68; β= -0.12; p=0.046), Caucasian men (R2=0.62; β= -0.24; p<0.001) and Caucasian
women (R2=0.72; β= -0.13; p=0.029). This implicates that renal function may be
detrimentally affected by L-citrulline concentrations.
In the Caucasian men and women negative correlations between eCCR and SDMA were
found before adjustments (r=-0.33; p=0.003 and r=-0.26; p=0.006, respectively). This
phenomenon was confirmed in the forward stepwise multiple regression analysis in
Caucasian men (R2=0.75; β= -0.27; p<0.001) and women (R2=0.73; β= -0.21; p<0.001),
while no associations were found in the Africans. This result is not unexpected, since SDMA
can only be eliminated by the kidneys and is therefore an important risk marker for the early
detection of renal dysfunction.
In Caucasian men we found that ADMA correlated with ACR (r=0.36; p=0.001), night-time
SBP (r=0.34; p=0.002) and night-time DBP (r=0.25; p=0.023) with single linear regression
analyses. A similar trend was shown in African men with night-time SBP (r= 0.20; p=0.089)
and night-time DBP (r= 0.21; p=0.078) respectively, but this association was absent in the
Caucasian and African women. After adjustments for age and body mass index, the
associations with ADMA, ACR and SBP in the Caucasian men remained. However, a
negative association between eCCR and ADMA also became evident in the African men (r=-
0.24; p=0.025) and remained significant in the forward stepwise multiple regression analysis
(R2=0.44; β= -0.18; p=0.034). It is, however, not clear why our results were gender specific,
but we could speculate that the female sex hormones may play a part in protecting the
vascular endothelium.
Apart from the associations described above, there were no significant independent
associations between the markers of the NO cycle (such as L-arginine) and PWV, cIMT,
eCCR, ACR or Cornell product.
In conclusion, although Africans presented a more vulnerable cardiovascular profile, we
found a consistent negative association between renal function and L-citrulline in all
participants, which has only been reported previously in patients with chronic renal disease.
Additionally we found a gender-specific link between renal function and ADMA in African and
Caucasian men. Our results may indicate that in the general population, markers of NO bioavailability
may be associated with early changes in renal function, accompanying elevated
blood pressure. / Thesis (MSc (Physiology))--North-West University, Potchefstroom Campus, 2013
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:nwu/oai:dspace.nwu.ac.za:10394/8719 |
| Date | January 2012 |
| Creators | Loots, Ilisma |
| Publisher | North-West University |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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