The effect of angiotensin II microinjection into the bed nucleus of the stria terminalis on serum lipid peroxidation and nitric oxide metabolite levels

Author

Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Overactivity of renin-angiotensin system is involved in the pathophysiology of renal and cardiovascular diseases. It is suggested that endothelial cells can release nitric oxide (NO) and reactive oxygen species in response to angiotensin II (Ang II). Angiotensin type 1 (AT1) receptor of Ang II has been found in the bed nucleus of the stria terminalis (BST). BST is involved in autonomic function. This study was performed to find the role of central Ang II in serum lipid peroxidation product and in releasing NO into circulation.
Materials and Methods: Twenty-one catheterized rats were placed in stereotaxic instrument. A hole was drilled above BST. In the control group, saline 0.9% (100 nl) was microinjected into the BST. In the second group, Ang II (100 μM, 100–150 nl) was microinjected into the BST. In the third group losartan (an AT1 antagonist) was microinjected (100 μM, 200 nl) before Ang II into the BST. Systolic blood pressure was recorded. The NO metabolite (nitrite) and malondialdehyde (MDA) were measured in the rat's serum.




Results: The data indicated that microinjection of Ang II into the BST produced a pressor response (P < 0.0001). It also increased MDA and nitrite levels of the serum significantly (P < 0.001, P < 0.0001). Pretreatment with losartan before Ang II microinjection attenuated serum's levels of MDA and nitrite (P < 0.001, P < 0.0001).
Conclusion: Our findings suggest that central effect of Ang II on blood pressure is accompanied with increased levels of MDA and nitrite in the circulation.

Keywords

1.
Dilauro M, Burns KD. Angiotensin-(1-7) and its effects in the kidney. Sci World J 2009;9:522-35.  Back to cited text no. 1
    
2.
De Mello WC, Danser AH. Angiotensin II and the heart: On the intracrine renin-angiotensin system. Hypertension 2000;35:1183-8.  Back to cited text no. 2
    
3.
Zucker IH, Xiao L, Haack KK. The central renin-angiotensin system and sympathetic nerve activity in chronic heart failure. Clin Sci (Lond) 2014;126:695-706.  Back to cited text no. 3
    
4.
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-9.  Back to cited text no. 4
    
5.
Thethi T, Kamiyama M, Kobori H. The link between the renin-angiotensin-aldosterone system and renal injury in obesity and the metabolic syndrome. Curr Hypertens Rep 2012;14:160-9.  Back to cited text no. 5
    
6.
Lund LH, Benson L, Dahlström U, Edner M. Association between use of renin-angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction. JAMA 2012;308:2108-17.  Back to cited text no. 6
    
7.
McKinley MJ, Albiston AL, Allen AM, Mathai ML, May CN, McAllen RM, et al. The brain renin-angiotensin system: Location and physiological roles. Int J Biochem Cell Biol 2003;35:901-18.  Back to cited text no. 7
    
8.
Xia H, Sriramula S, Chhabra KH, Lazartigues E. Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension. Circ Res 2013;113:1087-96.  Back to cited text no. 8
    
9.
Seyedi N, Xu X, Nasjletti A, Hintze TH. Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation. Hypertension 1995;26:164-70.  Back to cited text no. 9
    
10.
Dandona P, Kumar V, Aljada A, Ghanim H, Syed T, Hofmayer D, et al. Angiotensin II receptor blocker valsartan suppresses reactive oxygen species generation in leukocytes, nuclear factor-kappa B, in mononuclear cells of normal subjects: Evidence of an antiinflammatory action. J Clin Endocrinol Metab 2003;88:4496-501.  Back to cited text no. 10
    
11.
Giles TD, Sander GE, Nossaman BD, Kadowitz PJ. Impaired vasodilation in the pathogenesis of hypertension: Focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins. J Clin Hypertens 2012;14:198-205.  Back to cited text no. 11
    
12.
Terpolilli NA, Kim SW, Thal SC, Kataoka H, Zeisig V, Nitzsche B, et al. Inhalation of nitric oxide prevents ischemic brain damage in experimental stroke by selective dilatation of collateral arterioles. Circ Res 2012;110:727-38.  Back to cited text no. 12
    
13.
Drechsel DA, Estévez AG, Barbeito L, Beckman JS. Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS. Neurotox Res 2012;22:251-64.  Back to cited text no. 13
    
14.
Hitomi H, Kiyomoto H, Nishiyama A. Angiotensin II and oxidative stress. Curr Opin Cardiol 2007;22:311-5.  Back to cited text no. 14
    
15.
Schröder K, Zhang M, Benkhoff S, Mieth A, Pliquett R, Kosowski J, et al. Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase. Circ Res 2012;110:1217-25.  Back to cited text no. 15
    
16.
Schürmann C, Rezende F, Kruse C, Yasar Y, Löwe O, Fork C, et al. The NADPH oxidase Nox4 has anti-atherosclerotic functions. Eur Heart J 2015;36:3447-56.  Back to cited text no. 16
    
17.
Chrissobolis S, Banfi B, Sobey CG, Faraci FM. Role of Nox isoforms in angiotensin II-induced oxidative stress and endothelial dysfunction in brain. J Appl Physiol 2012;113:184-91.  Back to cited text no. 17
    
18.
Chrissobolis S, Faraci FM. The role of oxidative stress and NADPH oxidase in cerebrovascular disease. Trends Mol Med 2008;14:495-502.  Back to cited text no. 18
    
19.
Wang D, Chen Y, Chabrashvili T, Aslam S, Borrego Conde LJ, Umans JG, et al. Role of oxidative stress in endothelial dysfunction and enhanced responses to angiotensin II of afferent arterioles from rabbits infused with angiotensin II. J Am Soc Nephrol 2003;14:2783-9.  Back to cited text no. 19
    
20.
Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002;89:3A-9A.  Back to cited text no. 20
    
21.
Nickenig G, Harrison DG. The AT(1)-type angiotensin receptor in oxidative stress and atherogenesis: Part I: Oxidative stress and atherogenesis. Circulation 2002;105:393-6.  Back to cited text no. 21
    
22.
Allen AM, Zhuo J, Mendelsohn FA. Localization and function of angiotensin AT1 receptors. Am J Hypertens 2000;13(1 Pt 2):31S-8S.  Back to cited text no. 22
    
23.
Crestani CC, Alves FH, Gomes FV, Resstel LB, Correa FM, Herman JP. Mechanisms in the bed nucleus of the stria terminalis involved in control of autonomic and neuroendocrine functions: A review. Curr Neuropharmacol 2013;11:141-59.  Back to cited text no. 23
    
24.
Cruz F, Alves F, Leao R, Planeta CD, Crestani C. Role of the bed nucleus of the stria terminalis in cardiovascular changes following chronic treatment with cocaine and testosterone: A role beyond drug seeking in addiction? Neuroscience 2013;253:29-39.  Back to cited text no. 24
    
25.
Granjeiro EM, Gomes FV, Alves FH, Crestani CC, Corrêa FM, Resstel LB. Bed nucleus of the stria terminalis and the cardiovascular responses to chemoreflex activation. Auton Neurosci 2012;167:21-6.  Back to cited text no. 25
    
26.
Alves FH, Resstel LB, Correa FM, Crestani CC. Bed nucleus of the stria terminalis a1- and a2-adrenoceptors differentially modulate the cardiovascular responses to exercise in rats. Neuroscience 2011;177:74-83.  Back to cited text no. 26
    
27.
Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: What is the clinical significance? Hypertension 2004;44:248-52.  Back to cited text no. 27
    
28.
Alexander RW. Theodore cooper memorial lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: A new perspective. Hypertension 1995;25:155-61.  Back to cited text no. 28
    
29.
Baltatu OC, Campos LA, Bader M. Local renin-angiotensin system and the brain – A continuous quest for knowledge. Peptides 2011;32:1083-6.  Back to cited text no. 29
    
30.
Diz DI, Arnold AC, Nautiyal M, Isa K, Shaltout HA, Tallant EA. Angiotensin peptides and central autonomic regulation. Curr Opin Pharmacol 2011;11:131-7.  Back to cited text no. 30
    
31.
Mollnau H, Wendt M, Szöcs K, Lassègue B, Schulz E, Oelze M, et al. Effects of angiotensin II infusion on the expression and function of NAD(P) H oxidase and components of nitric oxide/cGMP signaling. Circ Res 2002;90:E58-65.  Back to cited text no. 31
    
32.
Lee DY, Wauquier F, Eid AA, Roman LJ, Ghosh-Choudhury G, Khazim K, et al. Nox4 NADPH oxidase mediates peroxynitrite-dependent uncoupling of endothelial nitric-oxide synthase and fibronectin expression in response to angiotensin II: Role of mitochondrial reactive oxygen species. J Biol Chem 2013;288:28668-86.  Back to cited text no. 32
    
33.
Wang G, Coleman CG, Glass MJ, Zhou P, Yu Q, Park L, et al. Angiotensin II type 2 receptor-coupled nitric oxide production modulates free radical availability and voltage-gated Ca2+currents in NTS neurons. Am J Physiol Regul Integr Comp Physiol 2012;302:R1076-83.  Back to cited text no. 33
    
34.
Albrecht D, Nitschke T, Von Bohlen Und Halbach O. Various effects of angiotensin II on amygdaloid neuronal activity in normotensive control and hypertensive transgenic [TGR(mREN-2) 27] rats. FASEB J 2000;14:925-31.  Back to cited text no. 34
    
35.
Rostami B, Nematbakhsh M, Pezeshki Z, Talebi A, Sharifi MR, Moslemi F, et al. Effect of testosterone on Cisplatin-induced nephrotoxicity in surgically castrated rats. Nephrourol Mon 2014;6:e21546.  Back to cited text no. 35
    
36.
Rajaei Z, Hadjzadeh MA, Nemati H, Hosseini M, Ahmadi M, Shafiee S. Antihyperglycemic and antioxidant activity of crocin in streptozotocin-induced diabetic rats. J Med Food 2013;16:206-10.  Back to cited text no. 36
    
37.
Zhang GX, Kimura S, Nishiyama A, Shokoji T, Rahman M, Abe Y. ROS during the acute phase of Ang II hypertension participates in cardiovascular MAPK activation but not vasoconstriction. Hypertension 2004;43:117-24.  Back to cited text no. 37
    
38.
Pagano PJ, Clark JK, Cifuentes-Pagano ME, Clark SM, Callis GM, Quinn MT. Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: Enhancement by angiotensin II. Proc Natl Acad Sci U S A 1997;94:14483-8.  Back to cited text no. 38
    
39.
Braga VA, Colombari E, Jovita MG. Angiotensin II-derived reactive oxygen species underpinning the processing of the cardiovascular reflexes in the medulla oblongata. Neurosci Bull 2011;27:269-74.  Back to cited text no. 39
    
40.
Kafami M, Nasimi A. Cardiovascular and single-unit responses to microinjection of angiotensin II into the bed nucleus of the stria terminalis in rat. Neuroscience 2015;300:418-24.  Back to cited text no. 40
    
41.
Nasimi A, Hatam M. The role of the cholinergic system of the bed nucleus of the stria terminalis on the cardiovascular responses and the baroreflex modulation in rats. Brain Res 2011;1386:81-8.  Back to cited text no. 41
    
42.
Boudaba C, Szabó K, Tasker JG. Physiological mapping of local inhibitory inputs to the hypothalamic paraventricular nucleus. J Neurosci 1996;16:7151-60.  Back to cited text no. 42
    
43.
Choi DC, Furay AR, Evanson NK, Ostrander MM, Ulrich-Lai YM, Herman JP. Bed nucleus of the stria terminalis subregions differentially regulate hypothalamic-pituitary-adrenal axis activity: Implications for the integration of limbic inputs. J Neurosci 2007;27:2025-34.  Back to cited text no. 43
    
44.
Seifi B, Kadkhodaee M, Bakhshi E, Ranjbaran M, Ahghari P, Rastegar T. Enhancement of renal oxidative stress by injection of angiotensin II into the paraventricular nucleus in renal ischemia-reperfusion injury. Can J Physiol Pharmacol 2014;92:752-7.  Back to cited text no. 44
    
45.
Zimmerman MC, Lazartigues E, Sharma RV, Davisson RL. Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circ Res 2004;95:210-6.  Back to cited text no. 45
    
46.
Gao L, Wang W, Li YL, Schultz HD, Liu D, Cornish KG, et al. Sympathoexcitation by central ANG II: Roles for AT1 receptor upregulation and NAD(P) H oxidase in RVLM. Am J Physiol Heart Circ Physiol 2005;288:H2271-9.  Back to cited text no. 46
    
47.
Sowers JR, Epstein M, Frohlich ED. Diabetes, hypertension, and cardiovascular disease: An update. Hypertension 2001;37:1053-9.  Back to cited text no. 47
    
48.
Nakayama I, Kawahara Y, Tsuda T, Okuda M, Yokoyama M. Angiotensin II inhibits cytokine-stimulated inducible nitric oxide synthase expression in vascular smooth muscle cells. J Biol Chem 1994;269:11628-33.  Back to cited text no. 48
    
49.
Siragy HM, Carey RM. The subtype-2 (AT2) angiotensin receptor regulates renal cyclic guanosine 3', 5'-monophosphate and AT1 receptor-mediated prostaglandin E2 production in conscious rats. J Clin Invest 1996;97:1978-82.  Back to cited text no. 49
    
50.
Pueyo ME, Arnal JF, Rami J, Michel JB. Angiotensin II stimulates the production of NO and peroxynitrite in endothelial cells. Am J Physiol 1998;274(1 Pt 1):C214-20.  Back to cited text no. 50
    
51.
Buga GM, Gold ME, Fukuto JM, Ignarro LJ. Shear stress-induced release of nitric oxide from endothelial cells grown on beads. Hypertension 1991;17:187-93.  Back to cited text no. 51
    
52.
Paniagua OA, Bryant MB, Panza JA. Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature: Diminished activity in hypertensive and hypercholesterolemic patients. Circulation 2001;103:1752-8.  Back to cited text no. 52
    
53.
Hirata Y, Satonaka H. Hypertension and oxidative stress. Japan Med Assoc J 2001;44:540-5.  Back to cited text no. 53
    
54.
Kontos HA, Wei EP, Dietrich WD, Navari RM, Povlishock JT, Ghatak NR, et al. Mechanism of cerebral arteriolar abnormalities after acute hypertension. Am J Physiol 1981;240:H511-27.  Back to cited text no. 54
[PUBMED]    
55.
Ungvari Z, Csiszar A, Huang A, Kaminski PM, Wolin MS, Koller A. High pressure induces superoxide production in isolated arteries via protein kinase C-dependent activation of NAD(P) H oxidase. Circulation 2003;108:1253-8.  Back to cited text no. 55
    
56.
Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P) H oxidase: Role in cardiovascular biology and disease. Circ Res 2000;86:494-501.  Back to cited text no. 56
    
57.
Schnackenberg CG, Welch WJ, Wilcox CS. Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable superoxide dismutase mimetic: Role of nitric oxide. Hypertension 1998;32:59-64.  Back to cited text no. 57
    
58.
Omar R, Nomikos I, Piccorelli G, Savino J, Agarwal N. Prevention of postischaemic lipid peroxidation and liver cell injury by iron chelation. Gut 1989;30:510-4.  Back to cited text no. 58
    
59.
Dimmeler S, Hermann C, Galle J, Zeiher AM. Upregulation of superoxide dismutase and nitric oxide synthase mediates the apoptosis-suppressive effects of shear stress on endothelial cells. Arterioscler Thromb Vasc Biol 1999;19:656-64.  Back to cited text no. 59
    
60.
Fleming I, Busse R. Signal transduction of eNOS activation. Cardiovasc Res 1999;43:532-41.  Back to cited text no. 60