Structural changes in cerebral arteries following nitric oxide deprivation: a comparison between normotensive and hypertensive rats

Nan K. Hsieh; Jia Y. Wang; Jiang C. Liu; Wei H. Lee; Hsing I. Chen

doi:10.1160/TH03-10-0610

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(01): 162-170
DOI: 10.1160/TH03-10-0610

Cell Signalling and Vessel Remodelling

Schattauer GmbH

Structural changes in cerebral arteries following nitric oxide deprivation: a comparison between normotensive and hypertensive rats

Authors

Nan K. Hsieh

¹Graduate Institute of Medical Sciences, National Defense Medical Center, National Defense University, Taipei, Taiwan
Jia Y. Wang

²Department of Physiology, National Defense Medical Center, National Defense University, Taipei, Taiwan
Jiang C. Liu

³Department of Biology and Anatomy, National Defense Medical Center, National Defense University, Taipei, Taiwan
Wei H. Lee

⁴Department of Pathology, National Defense Medical Center, National Defense University, Taipei, Taiwan
Hsing I. Chen

⁵Institute of Medical Sciences, Tzu Chi University; Hualien, Taiwan

Abstract

Summary

Chronic inhibition of nitric oxide (NO) synthesis with Nωnitro-L-arginine methyl ester (L-NAME) has become a model of hypertension. The purpose of this study was to evaluate the morphological changes of cerebral arteries in rats with genetic hypertension and hypertension induced by chronic NO deprivation. Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto strain (WKY) were given L-NAME (1 mg·ml-1) from age 5 to 7 or 9 weeks. We assessed vascular remodelling and arteriolar injury score (AIS) in various cerebral arteries using different immunohistochemical staining techniques. In WKY and SHR, L-NAME caused an elevation in tail cuff pressure (TCP). The increase in TCP was larger in SHR than in WKY. L-NAME decreased body weight, but increased heart weight in SHR.The lumen diameter and media cross-section area of internal carotid artery (ICA) in SHR were smaller than those in WKY, and further reduced in SHR and WKY after L-NAME treatment. These findings indicate that cerebral vascular remodelling occurs following chronic hypertension either from genetic origin or NO deprivation. L-NAME increased the media thickness in SHR, but not in WKY. This agent also caused an increase in cell volume density, AIS, and inflammatory cells infiltration in perivascular space with a negative growth index in ICA. The media/lumen ratio was higher in SHR than WKY, and further increased following L-NAME treatment. Diversified vascular remodelling occurred in hypertensive rats, but not in untreated WKY. In summary, these results suggest that NO deprivation and genetic hypertension cause vascular changes in various cerebral arteries.

Keywords

Hypertension - vascular remodelling - nitric oxide blockade - inflammatory cell - stroke

Full Text

References

References
1 O’Donell CJ, Ridker PM, Glynn RJ. et al. Hypertension and borderline isolated systolic hypertension increase risks of cardiovascular disease and mortality in male physicians. Circulation 1997; 95: 1132-7.
2 Hansson L, Zanchetti A, Carruthers SG. et al. for the HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. Lancet 1998; 351: 1755-62.
3 Pockley AG. Heat shock proteins, inflammation, and cardiovascular disease. Circulation 2002; 105: 1012-7.
4 Dahlof B, Lindholm LH, Hansson L. et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOPHypertension). Lancet 1991; 338: 1281-5.
5 Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991; 43: 109-42.
6 Mulvany MJ. Resistance vessels in hypertension. In: Swales JD. Eds. Textbook of Hypertension. Oxford: Blackwell Scientific Publications; 1994: 103-19.
7 Loscalzo J. Nitric oxide and vascular disease. N Engl J Med 1995; 333: 251-3.
8 Ribeiro MO, Antunes E, Nucci G. et al. Chronic inhibition of nitric oxide synthesis: A new model of arterial hypertension. Hypertension 1992; 20: 298-303.
9 Chu Y, Heistad DD, Kathryn K. et al. Quantification of Mrna for endothelial NO synthase in mouse blood vessels by real-time polymerase chain reaction. Arterioscl Thromb Vasc Biol 2002; 22: 611-6.
10 Ignarro LJ, Napoli C, Loscalzo J. Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide: An overview. Circ Res 2002; 90: 21-8.
11 Zhao Q, Egashira K, Inoue S. et al. Vascular endothelial growth factor is necessary in the development of arteriosclerosis by recruiting/activating monocytes in a rat model of long-term inhibition of nitric oxide synthesis. Circulation 2002; 105: 1110-5.
12 Baumbach GL, Dobrin PB, Hart MN. et al. Mechanics of cerebral arterioles in hypertensive rats. Circ Res 1988; 62: 56-64.
13 Mulvany MJ, Aalkjær C. Structure and function of small arteries. Physiol Rev 1990; 70: 921-61.
14 Bund SJ, West KP, Heagerty AM. Effects of protection from pressure on resistance artery morphology and reactivity in spontaneously hypertensive and Wistar-Kyoto rats. Circ Res 1991; 68: 1230-40.
15 Wang JY, Fenstermacher JD, Shum AY. Regional variations in structural and functional adaptations in cerebral vasculature in chronic hypertension. J Med Sci 1991; 11: 79-100.
16 Moncada S, Higgs EA. The L-arginine-nitric oxide pathway. N Eng J Med 1993; 329: 2002-13.
17 Hajdu MA, Baumbach G. Mechanics of large and small cerebral arteries in chronic hypertension. Am J Physiol 1994; 266: H1027-H1033.
18 Mulvany MJ, Baumbach GL, Aalkjaer C. et al. Vascular remodeling. Hypertension 1996; 28: 505-6.
19 Viedt C, Vogel J, Athanasiou T. et al. Monocyte chemoattractant protein induces proliferation and interleukin-6 production in human smooth muscle cells by differential activation of nuclear factor-κB and activator protein-1. Arterioscl Thromb Vasc Biol 2002; 22: 914-20.
20 Chen HI, Hu CT. Endogenous nitric oxide on arterial hemodynamics: a comparison between normotensive and hypertensive rats. Am J Physiol 1997; 273: H1816-H1823.
21 Schiffrin EL, Park JB, Intengan HD, Touys T. Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation 2000; 101: 1653-9.
22 Bots ML, Hoes AW, Koudstaal PJ. et al. Common carotid indima-media thickness and risk of stroke and myocardial infarction: the Rotterdam study. Circulation 1997; 96: 1432-7.
23 Ward MR, Pasterkamp G, Yeung AC. et al. Arterial remodeling: mechanisms and clinical implications. Circulation 2000; 102: 1186-91.
24 Dijkstra CD, Dopp EA, Joling P. et al. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1,ED2,and ED3. Immunology 1985; 54: 589-99.
25 Bendeck MP. Mining the myocardium with macrophage drills, a novel mechanism for revascularization. Circ Res 2000; 87: 341-3.
26 Mai M, Geiger H, Hilgers KF. et al. Early interstitial changes in hypertension-induced renal injury. Hypertension 1993; 22: 754-65.
27 Ono H, Ono Y, Frohlich ED. Nitric oxide synthase inhibition in spontaneously hypertensive rats: systemic, renal, and glomerular hemodynamics. Hypertension 1995; 26: 249-55.
28 Arnal JF, Amrani AIE, Chatellier G. et al. Cardiac weight in hypertension induced by nitric oxide synthase blockade. Hypertension 1993; 22: 380-7.
29 Sigmon DH, Carretero OA, Beierwaltes WH. Endothelium-derived relaxing factor regulates renin release in vivo. Am J Physiol 1992; 263: 256-61.
30 Alberola A, Pinilla JM, Quesada T. et al. Role of nitric oxide in mediating renal response to volume expansion. Hypertension 1992; 19: 780-4.
31 Raij L. Nitric oxide in hypertension: relationship with renal injury and left ventricular hypertrophy. Hypertension 1998; 31: 189-93.
32 Roman Mj, Saba PS, Pini R. et al. Parallel cardiac and vascular adaptation in hypertension. Circulation 1992; 86: 1909-18.
33 Godin D, Ivan E, Johnson C. et al. Remodeling of carotid artery is associated with increased expression of matrix metalloproteinases in mouse blood flow cessation model. Circulation 2000; 102: 2861-6.
34 Schiffrin EL. Effect of antihypertensive therapy on small artery structure in hypertensive patients. Hypertension 1995; 26: 716-7.
35 Koyanagi M, Egashira K, Kitamoto S. et al. Role of monocyte chemoattractant protein-1 in cardiovascular remodeling induced by chronic blockade of nitric oxide synthesis. Circulation 2000; 102: 2243-8.
36 McDonald DM, Munn L, Jain RK. Vasculogenic mimicry: how convincing, how novel, and how significant?. Am J Pathol 2000; 156: 383-7.
37 Moldovan NI, Goldschmidt-Clermont PJ, Parker-Thornburg J. et al. Contribution of monocytes/macrophages to compensatory neovascularization: the drilling of metalloelastase-positive tunnels in ischemic myocardium. Circ Res 2000; 87: 378-84.
38 Yang ZY, Duckers HJ, Sullivan NJ. et al. Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury. Nat Med 2000; 06: 886-90.
39 Langille BL. Arterial remodeling: relation to hemodynamics. Can J Physiol Pharmacol 1996; 74: 834-41.
40 Diep QN, Mabrouk ME, Cohn JS. et al. Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: Role of peroxisome proliferator-activated receptor-γ. Circulation 2002; 105: 2296-302.
41 Lowe G, Rumley A, Norrie J. et al. WOSKOP-S. Blood rheology, cardiovascular risk factors and cardiovascular disease: The West of Scotland Coronary Prevention Study. Thromb Haemost 2000; 84: 553-8.
42 Niu X, Smith CW, Kubes P. Intracellular oxidative stress induced by nitric oxide synthesis inhibition increases endothelial cell adhesion to neutrophils. Circ Res 1994; 74: 1133-40.