Hypertension is a major global health problem and is often termed the “silent killer” [1].  Worldwide, it is responsible for approximately 7.5 million deaths annually, accounting for 12.8% of all deaths. According to the WHO, the global prevalence is 24.1% in men and 20.1% in women. In India, prevalence rates range from 20–40% in urban areas and 12–17% in rural areas [2].

Despite advances in understanding, the pathophysiology of essential hypertension, which constitutes over 90% of cases, remains incompletely defined. Endothelial dysfunction plays a central role, contributing to increased vascular resistance, target organ damage, and cardiovascular morbidity[3,4].

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS) from L-arginine, is a critical mediator of vasodilation, platelet inhibition, and vascular smooth muscle regulation. Reduced bioavailability of NO is a consistent feature in hypertensives [5].

Asymmetric dimethylarginine (ADMA), a naturally occurring methylated arginine derivative, is an endogenous inhibitor of NOS. Elevated ADMA impairs NO synthesis, promotes vasoconstriction, and accelerates vascular injury. Several studies have linked ADMA to endothelial dysfunction and cardiovascular risk, but limited Indian data exist [6,7].

This study was designed to assess serum ADMA and NO levels in hypertensive patients versus healthy controls, and to determine their correlation.

This hospital-based case–control study was conducted over a period of two years in a Government Medical College.

• Cases (n = 110): Essential hypertensive patients, subdivided into:

• Group I: Hypertensives without microalbuminuria (n = 59).
• Group II: Hypertensives with microalbuminuria (n = 51).
• Controls (n = 62): Age- and sex-matched normotensive volunteers.

Inclusion Criteria

• Adults diagnosed with essential hypertension (JNC-8 criteria).
• Patients providing written informed consent.

Exclusion Criteria

• Secondary hypertension (renal, endocrine, cardiovascular).
• Diabetes mellitus or endocrine disorders.
• Alcoholics, smokers, congenital CVD, or known CVD.

Sample Collection

• Blood samples: 5 ml fasting venous blood collected.
• Biochemical assays:
• Serum ADMA by ELISA.
• Serum NO by Griess method.
• Lipid profile, urea, creatinine by enzymatic kits.

Statistical Analysis

SPSS v19 was used. Data expressed as mean ± SD. Student’s t-test and ANOVA applied. Correlations tested with Pearson’s r. p < 0.05 considered significant.

Table 1: Baseline Characteristics and Blood Pressure

Figure 1: Comparison of mean SBP and DBP among controls, Group I and Group II.

Table 2: Serum ADMA and NO Concentrations

Figure 2: Mean serum ADMA and NO concentrations across groups.

Correlation Analysis

• ADMA vs NO: r = –0.732, p < 0.001 (strong negative correlation).

Figure 3: Scatter plot showing inverse correlation of ADMA and NO.

Our findings show significantly elevated serum ADMA levels and reduced NO concentrations in hypertensives compared to controls, with a strong inverse correlation.

This aligns with a study by Cooke et al., in 2000, who proposed ADMA as a key mediator of endothelial dysfunction [6]. Sibal et al., in 2010 and Perticone et al. in 2005 demonstrated raised ADMA in essential hypertension, confirming our observations [7,8].

Reduced NO levels are consistent with findings by Sun J et al. in 2003 and Helms & Kim-Shapiro in 2013, suggesting impaired NO synthesis and increased oxidative degradation in hypertensives [9,10].

Mechanistically, ADMA competes with L-arginine for NOS, leading to reduced NO production. Additionally, ADMA may enhance oxidative stress and activate the renin-angiotensin system, further elevating blood pressure.

Clinical Implications

• ADMA could be a non-invasive biomarker for endothelial dysfunction.
• Monitoring ADMA may allow early identification of high-risk hypertensives.
• Therapeutic strategies targeting ADMA metabolism (e.g., DDAH activators) may restore endothelial function.

Essential hypertension is associated with elevated ADMA and reduced NO, confirming endothelial dysfunction. ADMA is strongly inversely correlated with NO, reinforcing its role as a potential biomarker and therapeutic target in hypertension.

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