Effect of Lisinopril on Left Ventricular and Vascular Function in Nitric Oxide-Deficient Rats

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Metee Iampanichakul
Nisita Chaihongsa
Benchaporn Saengak
Weerapon Sangartit
Putcharawipa Maneesa
Parichat Prachaney
Poungrat Pakdeechote


Background and Objective: Lisinopril, angiotensin-converting enzyme inhibitors (ACEIs), is widely used to treat hypertension and heart failure. This study investigated whether lisinopril could prevent Nω-Nitrol-arginine methyl ester (L-NAME)-induced hypertension, left ventricular (LV) and vascular dysfunction in rats.

Methods: Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg/day) in drinking water only or together with lisinopril (2.5 mg/kg/day) for five weeks while control rats received distilled water (n=5). Blood pressure and cardiac function were measured. Aortic rings were isolated for vascular function test.

Results: Rats treated with L-NAME had high blood pressure and impairment of cardiac function and acetylcholine (ACh)-induced vasorelaxation in isolated aortic rings. Vascular response to sodium nitroprusside (SNP) did not differ among groups. Interestingly, lisinopril significantly prevented L-NAME-induced hypertension and alleviated L-NAME-induced cardiac and vascular dysfunction (p<0.05).

Conclusion: These findings suggested that lisinopril prevented the development of hypertension and partially prevented cardiac and vascular endothelial dysfunction induced by L-NAME.


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1. Azevedo PS, Polegato BF, Minicucci MF, Paiva SA, Zornoff LA. Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment. Arq Bras Cardiol. 2016; 106: 62-9.
2. Aronow WS, Ahn C, Kronzon I, Koenigsberg M. Congestive heart failure, coronary events and atherothrombotic brain infarction in elderly blacks and whites with systemic hypertension and with and without echocardiographic and electrocardiographic evidence of left ventricular hypertrophy. Am J Cardiol. 1991; 67: 295-9.
3. Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv Exp Med Biol. 2017; 956: 511-40.
4. Tsuda K. Renin-Angiotensin system and sympathetic neurotransmitter release in the central nervous system of hypertension. Int J Hypertens. 2012; 2012: 474870.
5. Ghiadoni L, Taddei S, Virdis A. Hypertension and endothelial dysfunction: therapeutic approach. Curr Vasc Pharmacol. 2012; 10(1): 42-60.
6. Jacobsen JC, Hornbech MS, Holstein-Rathlou NH. Significance of microvascular remodelling for the vascular flow reserve in hypertension. Interface Focus. 2011; 1: 117-31.
7. Abdel-Rahman RF, Hessin AF, Abdelbaset M, Ogaly HA, Abd-Elsalam RM, Hassan SM. Antihypertensive Effects of Roselle-Olive Combination in L-NAME-Induced Hypertensive Rats. Oxid Med Cell Longev. 2017; 2017: 9460653.
8. Wunpathe C, Maneesai P, Rattanakanokchai S, Bunbupha S, Kukongviriyapan U, Tong-un T, et al. Tangeretin mitigates L-NAME-induced ventricular dysfunction and remodeling through AT1R/pERK1/2/pJNK signaling pathway in rats. Food & Function. 2020.
9. Maneesai P, Prasarttong P, Bunbupha S, Kukongviriyapan U, Kukongviriyapan V, Tangsucharit P, et al. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in L-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT(1)R Expression. Nutrients. 2016; 8(3): 122.
10. Messerli FH, Bangalore S, Bavishi C, Rimoldi SF. Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use? Journal of the American College of Cardiology. 2018; 71: 1474-82.
11. Robles N, Cerezo I, Gallego R. Renin-Angiotensin System Blocking Drugs. Journal of cardiovascular pharmacology and therapeutics. 2013; 19.
12. Powers ER, Chiaramida A, DeMaria AN, Giles TD, Hackshaw B, Hart W, et al. A double-blind comparison of lisinopril with captopril in patients with symptomatic congestive heart failure. J Cardiovasc Pharmacol. 1987; 9 Suppl 3: S82-8.
13. De Gennaro Colonna V, Fioretti S, Rigamonti A, Bonomo S, Manfredi B, Muller EE, et al. Angiotensin II type 1 receptor antagonism improves endothelial vasodilator function in L-NAME-induced hypertensive rats by a kinin-dependent mechanism. Journal of Hypertension. 2006; 24: 95-102.
14. Cunha RS, Cabral AM, Vasquez EC. Evidence that the autonomic nervous system plays a major role in the L-NAME-induced hypertension in conscious rats. Am J Hypertens. 1993; 6(9): 806-9.
15. Souza HC, Ballejo G, Salgado MC, Da Silva VJ, Salgado HC. Cardiac sympathetic overactivity and decreased baroreflex sensitivity in L-NAME hypertensive rats. Am J Physiol Heart Circ Physiol. 2001; 280: H844-50.
16. Potue P, Wunpathe C, Maneesai P, Kukongviriyapan U, Prachaney P, Pakdeechote P. Nobiletin alleviates vascular alterations through modulation of Nrf-2/HO-1 and MMP pathways in l-NAME induced hypertensive rats. Food Funct. 2019; 10: 1880-92.
17. Jin S, Teng X, Xiao L, Xue H, Guo Q, Duan X, et al. Hydrogen sulfide ameliorated L-NAME-induced hypertensive heart disease by the Akt/eNOS/NO pathway. Exp Biol Med (Maywood). 2017; 242: 1831-41.
18. Jan-On G, Sangartit W, Pakdeechote P, Kukongviriyapan V, Sattayasai J, Senaphan K, et al. Virgin rice bran oil alleviates hypertension through the upregulation of eNOS and reduction of oxidative stress and inflammation in L-NAME-induced hypertensive rats. Nutrition. 2019; 69: 110575.
19. Combe C, McCullough KP, Asano Y, Ginsberg N, Maroni BJ, Pifer TB. Kidney Disease Outcomes Quality Initiative (K/DOQI) and the Dialysis Outcomes and Practice Patterns Study (DOPPS): nutrition guidelines, indicators, and practices. Am J Kidney Dis. 2004; 44(5 Suppl 2): 39-46.