Relationship of lisinopril with kallikrein-kinin system in hypertensive patients in Erbil city, Iraq
Background and objective: Hypertension is characterized by a persistent, progressive elevation in blood pressure. Oxidative stress and endothelial dysfunction have a role in the pathogenesis of hypertension through interaction with the elements of the renin-angiotensin system. This study aimed to examine the effects of lisinopril on mean arterial pressure and biosubstances of Kallikrein-kinin-system (bradykinin), endothelial dysfunction (nitric oxide), and oxidative stress (malondialdehyde).
Methods: A clinical trial was conducted in Erbil city from December 1st, 2015 to August 10th, 2016. The study included 65 patients with essential hypertension and 25 apparently healthy subjects; their ages were in between 18 and 55 years. The patients were receiving 10 mg lisinopril orally per day for six weeks as a starting dose.
Results: At hypertension diagnosis, patients were with lower bradykinin and nitric oxide levels when compared with apparently healthy subjects; however, malondialdehyde level showed no significant difference when compared with of healthy subjects. After six weeks patients treatment, comparing bradykinin, nitric oxide, and malondialdehyde mean levels with their baselines, showed that significantly increased in bradykinin and nitric oxide (P <0.01) and significantly decreased in malondialdehyde (P <0.01). On the other hand, the differences between after treatment and healthy subjects had no significant difference, except bradykinin. Eventually, during treatment, the mean arterial pressure was significantly lowered.
Conclusion: in addition to the significant lowering of blood pressure, lisinopril 10 mg daily for six weeks can significantly elevate kallikrein-kinin system and endothelial dysfunction markers, and significantly lowered in oxidative stress marker in hypertensive Kurd patients in Erbil city.
Williams SF, Nicholas SB, Vaziri ND, Norris KC. African Americans, hypertension and the renin angiotensin system. World J Cardiol 2014; 6(9):878–89.
Dufton J. The pathophysiology and pharmaceutical treatment of hypertension. PharmCon, Inc; 2011.
Kasko M, Budaj M, Hulin I. Harmful or helpful hypertension–pathophysiological basis. Slovakia: Bratislava Comenius University. Genetics and Pathophysiology of Essential Hypertension. Khullar M, editors. Hypertension, 1st ed. Rijeka, Croatia: InTech; 2012. P. 9.
Moon JY. Recent update of renin-angiotensin-aldosterone system in the pathogenesis of hypertension. Electrolyte Blood Press 2013; 11(2):41–5.
Unger T, Paulis L, Sica DA. Therapeutic perspectives in hypertension: novel means for renin–angiotensin–aldosterone system modulation and emerging device-based approaches. Eur Heart J 2011; 32(22):2739–47.
Flores-Munoz M, Work LM, Douglas K, Denby L, Dominiczak AF, Graham D, et al. Angiotensin- (1-9) attenuates cardiac fibrosis in the stroke-prone spontaneously hypertensive rat via the angiotensin type 2 receptor. Hypertens 2012; 59(2):300–7.
Luo H, Wang X, Chen C, Wang J, Zou X, Li C, et al. Oxidative stress causes imbalance of renal renin angiotensin system (RAS) components and hypertension in obese Zucker rats. J Am Heart Assoc 2015; 4(2):e001559.
Camargo AC, Ianzer D, Guerreiro JR, Serrano SM. Bradykinin-potentiating peptides: beyond captopril. Toxicon 2012; 59(4):516–23.
Virdis A, Ghiadoni L, Taddei S. Effects of antihypertensive treatment on endothelial function. Curr Hypertens Rep 2011; 13(4):276–81.
Bell K, Twiggs J, Olin BR. Hypertension: The Silent Killer: Updated JNC-8 Guideline Recommendations. Alabama pharmacy association: Contining education; 2015. P. 1–8.
Al Ghatrif M, Kuo YF, Al Snih S, Raji MA, Ray LA, Markides KS. Trends in hypertension prevalence, awareness, treatment and control in older Mexican Americans, 1993–2005. Ann Epidemiol 2011; 21(1):15–25.
Gu Q, Burt VL, Dillon CF, Yoon S. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension the National Health and Nutrition Examination Survey, 2001 to 2010. Circ 2012; 126(17):2105–14.
Muslih AI. Reduction of mean arterial pressure and proteinuria by the effect of aceis (lisinopril) in Kurdish hypertensive patients in Hawler city. Glob J Health Sci 2012; 4(5):14.
Saul SM, Duprez DA, Zhong W, Grandits GA, Cohn JN. Effect of carvedilol, lisinopril and their combination on vascular and cardiac health in patients with borderline blood pressure: the DETECT Study. J Hum Hypertens 2013; 27(6):362–7.
Kayashima Y, Smithies O, Kakoki M. Kinins—The Kallikrein-Kinin System and Oxidative Stress. Curr Opin Nephrol Hypertens 2012; 21(1):92–6.
Schulz E, Gori T, Münzel T. Oxidative stress and endothelial dysfunction in hypertension. Hypertens Res 2011; 34(6):665–73.
Regoli D, Gobeil F. Critical insights into the beneficial and protective actions of the kallikrein–kinin system. Vascul Pharmacol 2015; 64:1–10.
Kohno M, Yokokawa K, Minami M, Yasunari K, Maeda K, Kano H, et al. Plasma levels of nitric oxide and related vasoactive factors following long-term treatment with angiotensin-converting enzyme inhibitor in patients with essential hypertension. Metab 1999; 48(10):1256–9.
Kaminskii YG, Suslikov AV, Tikhonova LA, Galimova MK, Ermakov GL, Tsvetkov VD, et al. Arginase, nitrates, and nitrites in the blood plasma and erythrocytes in hypertension and after therapy with lisinopril and simvastatin. Biol Bull 2011; 38(5):446–52.
Kosenko E, Tikhonova L, Suslikov A, Kaminsky Y. Impacts of lisinopril and lisinopril plus simvastatin on erythrocyte and plasma arginase, nitrite, and nitrate in hypertensive patients. J Clin Pharmacol 2012; 52(1):102–9.
Velayutham PK, Adhikary SD, Babu SK, Vedantam R, Korula G, Ramachandran A. Oxidative stress–associated hypertension in surgically induced brain injury patients: Effects of β-blocker and angiotensin-converting enzyme inhibitor. J Surg Res 2013; 179(1):125–31.
Kelly AS, Gonzalez‐Campoy JM, Rudser KD, Katz H, Metzig AM, Thalin M, et al. Carvedilol‐Lisinopril Combination Therapy and Endothelial Function in Obese Individuals With Hypertension. J Clin Hypertens 2012; 14(2):85–91.
Kirbas S. Effect of lisinopril on oxidative stress in brain tissues of rats with L-Name induced hypertension. Turk J Biochem 2013; 38(2):163–8.
Albarwani S, Al-siyabi S, Al-husseini I, Al-ismail A, Al-lawati I, Al-bahrani I, et al. Lisinopril alters contribution of nitric oxide and KCa channels to vasodilatation in small mesenteric arteries of spontaneously hypertensive rats. Physiol Res 2015; 64:39–49.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The copyright on any article published in Zanco J Med Sci is retained by the author(s) in agreement with the Creative Commons Attribution Non-Commercial ShareAlike License (CC BY-NC-SA 4.0).