Asymmetric dimethylarginine levels in dipper and nondipper hypertensive patients

Abstract

Objectives: Asymmetric Dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthesis and also is an indicator of endothelial dysfunction. Patients who have nondipper blood pressure pattern have been shown to exhibit more endothelial dysfunction than patients who has dipper blood pressure pattern. However, other en­dogenous markers, but not ADMA, are used to assess endothelial function in these studies. In our study, we used ADMA levels to compare differences in endothelial function between each groups. Materials and methods: This study includes 87 patients who admitted to Düzce University internal medicine and Cardiology outpatient clinics throughout 6 months and have been diagnosed previously as essential hyperten­sion and followed with medical therapy. Patients were di­vided into two groups as non-dippers and dippers, using ambulatory blood pressure measurement. Patients\' body mass index, Systolic blood pressure and diastolic blood pressure, triglycerides, total cholesterol, low density lipo­protein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and ADMA levels were measured. Results: Age, BMI, and lipid values did not differ sig­nificantly between groups (p>0.05). Mean ADMA level was 1.29±0.13 in dippers, and that of non-dippers was 1.27±0.13μmol/L. ADMA levels did not differ significantly between the non-dipper and dipper groups (p=0.575). Conclusion: ADMA levels were found to be higher in hypertensive patients due to endothelial dysfunction. En­dothelial dysfunction was more frequent in patients who had nondipper blood pressure pattern than patients who had dipper blood pressure pattern. In our study, ADMA levels did not differ significantly between two patterns.

Keywords

• Dipper-Hypertension, Non-Dipper-Hyperten­sion, ADMA

Dipper ve nondipper hipertansiyon hastalarında asimetrik dimetil arjinin düzeyleri

Abstract

Amaç: Asimetrik dimetil arjinin (ADMA), nitrik oksit sen­tezinin endojen bir inhibitörü olup aynı zamanda endotel disfonksiyonunun bir göstergesidir. Non-dipper hipertan­siyon (HT) tipine sahip hastalarda yapılan çalışmalarda endotel disfonksiyonun dolayısıyla hedef organ hasarının dipper HT tipi olan hastalardan daha fazla olduğu göste­rilmiştir. Biz çalışmamızda bu iki grup arasında endotel fonksiyonu değişikliklerini ADMA seviyelerine bakarak karşılaştırdık. Gereç ve yöntem: Bu çalışmaya 6 ay içerisinde Düzce Üniversitesi Tıp Fakültesi iç hastalıkları ve kardiyoloji po­likliniğine başvuran ve daha önceden esansiyel HT tanı­sı konulup medikal tedavi ile takip edilen 87 hasta dahil edildi. Hastalar ambulatuar kan basıncı ölçümü yapıla­rak dipper ve non-dipper olmak üzere iki gruba ayrıldı. Hastaların vucut kitle indeksi(VKİ), sistolik kan basıncı ve diyastolik kan basıncı, trigliserid, total kolesterol, dü­şük dansiteli lipoprotein(LDL) kolesterol, yüksek dansiteli lipoprotein(HDL) kolesterol ve ADMA ölçümleri yapıldı. Bulgular: Grupların yaş, VKİ ve lipid değerleri arasında istatistiksel olarak fark yoktu (p>0.05). Dipper grubunda bakılan ADMA seviyeleri 1.29±0.17 μmol/L, non-dipper grubunda ise 1.27±0.13 μmol/L idi. Dipper ve non-dipper grupları arasında ADMA açısından anlamlı farlılık yoktu (p=0.575). Sonuç: ADMA seviyeleri HT hastalarında bozulmuş en­dotel fonksiyonuna bağlı olarak yüksek olarak bulunur. Kan basıncının non-dipper tipinde endotel disfonksiyonu dipper tipi olanlara göre daha fazladır. Çalışmamızda iki tip arasında ADMA seviyelerinde farklılık bulunamamış­tır.

Keywords

• Dipper Hipertansiyon, Non-Dipper Hipertansiyon, ADMA

References

1. Millar-Craig MW, Bishop CN, Raftery EB. Circadian varia- tion of blood-pressure. Lancet 1978;1:795-7.
2. Seo WS, Oh HS. The circadian rhythms of blood pressure and heart rate in the hypertensive subjects: dippers and non- dippers. Yonsei Med J 2002;43:320-8.
3. Fujii T, Uzu T, Nishimura M, Takeji M, et al. Circadian rhythm of natriuresis is disturbed in nondipper type of es- sential hypertension. Am J Kidney Dis 1999;33:29-35.
4. Kurpesa M, Trzos E, Drozdz J, Bednarkiewicz Z, Krzemins- ka-Pakula M. Myocardial ischemia and autonomic activity in dippers and non-dippers with coronary artery disease: as- sessment of normotensive and hypertensive patients. Int J Cardiol 2002; 83:133-42.
5. Vallance P. Importance of asymmetrical dimethylarginine in cardiovascular risk. Lancet 2001;358:2096-7.
6. Surdacki A, Nowicki M, Sandmann J, et al. Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension. J Cardiovasc Pharmacol 1999; 33: 652-8.
7. Boeger RH, Bode-Boeger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): A novel risk factor for endothe- lial dysfunction: Its role in hypercholesterolemia. Circula- tion 1998; 98: 1842-7.
8. Miyazaki H, Matsuoka H, Cooke JP, et al. Endogenous nitric oxide synthase inhibitor: A novel marker of atherosclerosis. Circulation 1999; 99: 1141-6.

9. Boeger RH, Bode-Boeger SM, Thiele W, et al. Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 1997; 95: 2068-74.
10. Usui M, Matsuoka H, Miyazaki H, Ueda S, Okuda S, Imaizumi T. Increased endogenous nitric oxide synthase inhibitor in patients with congestive heart failure. Life Sci 1998;62:2425-30.
11. Matsuoka H, Itoh S, Kimoto M, et al. Asymmetrical dimeth- ylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension. Hypertension 1997;29:242-47.
12. Kielstein JT, Bode-Böger SM, Frölich JC, Ritz E, Haller H, Fliser D. Asymmetric dimethylarginine, blood pres- sure, and renal perfusion in elderly subjects. Circulation. 2003;107(14):1891-5.
13. García-Ortiz L, Gómez-Marcos MA, Martín-Moreiras J, et al. Pulse pressure and nocturnal fall in blood pressure are predictors of vascular, cardiac and renal target organ damage in hypertensive patients (LOD-RISK study). Blood Press Monit. 2009;14:145-51.
14. Ito A, Egashira K, Narishige T, Muramatsu K, Takeshita A. Renin-Angiotensin system is involved in the mechanism of increased serum asymmetric dimethylarginine in essential hypertension. Jpn Circ J 2001;65:775-8.
15. Guagnano MT, Ferroni P, Santilli F, et al. Determinants of platelet activation in hypertensives with microalbuminuria. Free Radic Biol Med. 2009;46:922-7.
16. Tsioufis C, Dimitriadis K, Andrikou E, et al. ADMA, C- reactive protein, and albuminuria in untreated essential hypertension: A Cross-sectional Study. Am J Kidney Dis 2010; 55:1050-9.
17. Oguz A, Uzunlulu M. Short term fluvastatin treatment low- ers serum asymmetric dimethylarginine levels in patients with metabolic syndrome. Int Heart J 2008;49:303-11.
18. Higashi Y, Nakagawa K, Kimura M, et al. Circadian varia- tion of blood pressure and endothelial function in patients with essential hypertension: a comparison of dippers and non-dippers. J Am Coll Cardiol 2002;40:2039-43.
19. Kielstein JT, Böger RH, Bode-Böger SM, et al. Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: Relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol 1999; 10: 594-600.
20. Tanaka N, Katayama Y, Katsumata T. Effects of long-term administration of HMG-CoA reductase inhibitor, atorvasta- tin, on stroke events and local cerebral blood flow in stroke- prone spontaneously hypertensive rats. Brain Res 2007; 12: 125-32.
21. Vallance P. The asymmetrical dimethylarginine/dimethy- larginine dimethylamino-hydrolase pathway in the regula- tion of nitric oxide production. Clin Sci 2001; 100: 159- 60.
22. Lentz SR, Rodionov RN, Dayal S. Hyperhomocysteinemia, endothelial dysfunction, and cardiovascular risk: the poten- tial role of ADMA. Atherosclerosis Suppl 2003; 4: 61-5.
23. Erdem S, Ünlü A. Asimetrik dimetilarjinin ve klinik önemi. Selçuk Tıp Derg 2009;25:107-15.