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Effect of Chronic Inhibition of Nitric Oxide on Blood Pressure and Apoptosis in the Blood Pressure-Associated with Organs  

Bae, Hyung-Joon (Department of Laboratory, Georgia Medical Center)
Abstract
Sprague-Dawley(SD) rats were orally administered with $N^G$-nitro-L-arginine methyl ester(L-NAME) which inhibits or blocks the production of nitric oxide from L-arginine in vascular endothelial cells and vessel tissue to statistically examine the effects of nitric oxide on some physiological changes such as blood pressure and heart rate, and to confirm the apoptosis induced by the suppressed nitric oxide activity in some related organs under light microscope. Systolic blood pressure significantly increased 28.5% by the chronic treatment of L-NAME for 8 weeks (P<0.001), no significant difference, however, was observed in heart rate between the control group and the L-NAME-treated group regardless of their age. Hematoxylin-eosin staining showed some histological alterations only in kidney among the examined organs; heart, liver, pancreas, and adrenal gland from the L-NAME-treated group. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) test showed a strong positive reaction, representing that the chronic treatment of L-NAME facilitates apoptosis, in the cortex and medulla of kidney, but not any significance detectable in the other organs. These results conclude that chronic treatment of L-NAME significantly increases blood pressure, and that the followed inhibition of nitric oxide synthesis occurs a typical inducement of apoptosis in kidney.
Keywords
L-NAME; Nitric oxide; Chronic inhibition; Blood pressure; Apoptosis; TUNEL test; PCNA;
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1 Morris GF, Mathews MB. Regulation of proliferating cell nuclear antigen during the cell cycle. J Bioi Chem. 1989. 264: 13856 -13864.
2 Cotran RS, Kumar V, Robbins SL. Pathologic basis of disease. Pathologic basis of disease. 1994. pp. 17-21. WB Saunders Co. Philadelphia, USA.
3 Chung M-J, Jang K-Y, Kang M-J, Lee D-G, Oh B-C. Expression of apoptosis, bcl-2, and PCNA in uterine cervical intraepithelial neoplasia and invasive carcinoma. Kor J Pathol. 1997. 31(10): 1180-1189.
4 Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nuclear antigen in proliferating cells. J Immunol. 1978. 121: 2228-2234.
5 Moncada S, Higgs EA. Molecular mechanism and therapeutic strategies related to nitric oxide. FASEB J. 1995. 9: 1319-1330.   DOI
6 Martin-Partido G, Alvarez IS, Rodriguez-Gallardo L, Navascues J. Differential staining of dead and dying embryonic cells with a simple new technique. J Microsc. 1986. 142: 101-106.   DOI
7 Bursh W, Taper HS, Lauer B, Schulte-Hermann R. Quantitive histological and histochemical studies on the occurrence and stages of controlled cell death(apoptosis) during regression of rat liver hyperplasia. Arch Cell Pathol. 1985. 50: 153-166.
8 Bursztyn M, Raz I, Meker J, Ishay BD. Effect of acute N-nitro-L-arginine methyl ester (L-NAME) hypertension on glucose tolerance, insulin levels, and $\left[^{3}H \right]$-deoxyslucose muscle uptake. Am J Hypertens. 1997. 10(6): 683-686.   DOI   ScienceOn
9 Brune B, von Knethen A, Sandau KB. Nitric oxide (NO): an effect of apoptosis. Cell Death Differ. 1999. 6: 969-975.   DOI   ScienceOn
10 Busse R, Fleming I, Schini VB. Nitric oxide formation in the vascular wall: regulation and function implications Annu Rev Pharmacol Toxicol. 1995. 35: 7-18.
11 Kelly JJ, Tam SH, Williamson PM, Lawson J, Whitworth JA. The nitric oxide system and cortisol-induced hypertension in humans. Clin Exp Pharmacol Physiol. 1998. 25(11): 945-946.   DOI   ScienceOn
12 Baylis C, Mitruka B, Deng A. Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage. J Clin Invest. 1992. 90: 278-281.   DOI
13 Lin KF, Chao L, Chao J. Prolonged reduction of high blood pressure with human nitric oxide synthase gene delivery. Hypertension. 1997. 30(3): 307-313.   DOI   ScienceOn
14 Arnal IF, Warin L, Michel JB. Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase. J Clin Invest. 1992. 90: 647-652.   DOI
15 Liu L, Stamler JS. NO: an inhibitor of cell death. Cell Death Differ. 1999. 6: 937-942.   DOI   ScienceOn
16 Lanthelme P, Lo M, Sassard J. Decreased cardiac baroreflex sensitivity is not due to cardiac hypertrophy in $N^{G}$-nitro-Larginine methyl ester-induced hypertension. J Hypertens. 1994.12(7): 791-795.
17 Zou AP, Jr Cowely AW. Nitric oxide in renal cortex and medulla: an in vivo microdialysis study. Hypertension. 1997. 29(2): 194 -198.   DOI
18 Kohl V, Seizner M, Madden JF, Bentley RC, Clavien PA. Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver. Transplantation. 1999. 67: 1099-1105.   DOI   ScienceOn
19 Kerr JFR. Some lysosome functions in liver cells reacting to sublethal injury. In: Dingle JT, Fell HB eds. Lysosomes in biology and pathology. 1972. pp. 126-142. North-Holland. Amsterdam, Denmark.
20 Yin N, Kaestle S, Yin J, Hentschel T, Pries AR, Kuppe H, Kuebler WM. Inhaled nitric oxide versus aerosolized iloprost for the treatment of pulmonary hypertension with left heart disease. 2009. Crit Care Med 37(3): 980-986.   DOI   ScienceOn
21 Wijsman JH, Jonker RR, Keijzer R, Van De velde CJH, Comelisse CJ, Van dierendonck JH. A new method to detect apoptosis in paraffin sections: in suit end-labelling of fragmented DNA. J Histochem Cytochem. 1993. 41: 7-12.   DOI   ScienceOn
22 Wang YF, Tian H, Tang CS, Jin HF, Du JB. Nitric oxide modulates hypoxic pulmonary smooth muscle cell proliferation and apoptosis by regulating carbon monoxide pathway. Acta Pharmacol Sin. 2007. 28(1): 28-35.   DOI   ScienceOn
23 Susin SA, Zamzami N, Castedo M. Daugas E, Wang HG, Geley S. Fassy F, Reed JC, Kroemer Reed. The central execution of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-l/CD95 and ceramide-induced apoptosis. J Exp Med. 1997. 186: 25-37.   DOI   ScienceOn
24 Thomas GL, Yang B, Wagner BE, Savill J, El Nahas AM. Celluar apoptosis and proliferation in experimental renal fibrosis. 1998. Nephrol Dial Transplant. 13(9): 2216-2226.   DOI
25 Sigmon DH, Beierwaltes WH. Influence of nitric oxide in the chronic phase of two-kidney, one clip renovascular hypertension. Hypertension. 1998. 31: 649-656.   DOI   ScienceOn
26 Hockenbery D. Defining apoptosis. Am J Pathol. 1995. 146: 16-19.
27 Kaneto H, Jujii J, Seo HG, Suzuki K, Matsuoka T, Nakamura M, Tatsumi H, Yamasaki Y, Kamada T, Taniguchi N. Apoptotic cell death triggered by nitric oxide in pancreatic beta-cells. Diabetes. 1995. 44: 733-738.   DOI   ScienceOn
28 Jover B, Herizi A, Ventre F, Dupont M, Mimran A. Sodium and angiotensin in hypertension induced by long-term nitric oxide blockade. Hypertension. 1993. 21: 944-948.   DOI   ScienceOn
29 Jang TJ, Jung W-H, Lee K-G. The relation between cell proliferation and apoptosis according to the histologic types in chemically induced rat mammary tumorigenesis. Kor J Pathol. 1998. 32(3): 174-185.
30 Ikeda K, Jr Gutierrez OG, Yamori Y. Dietary $N^{G}$-nitro-L-arginine induces sustained hypertension in normotensive Wistar-Kyoto rats. Clin Exp Pharmacol Physiol. 1992. 19(8): 583-586.   DOI
31 Olatunji LA, Soladove AO. Oral contraceptive administration aggravates nitric oxide synthesis inhibition-induced high blood pressure in female rats. 2008. Pathophysiology. 15(4): 221-226.   DOI   ScienceOn
32 Muhl H, Sandau K, Brune B, Briner VA, Pfeilschifter J. Nitric oxide donors induce apoptosis in glomerular mesangial cells, epithelial cells and endothelial cells. Eur J Pharmacol. 1996. 317: 137-149.   DOI   ScienceOn
33 Gazitt Y, Erdos Gw. Fluctuations and ultrastructural localization of oncoproteins and cell cycle regulatory proteins during growth and apoptosis of synchronized AGF cells. Cancer Res. 1994. 54: 950-956.
34 Goldberg MT, Tackaberry LE, Hardy MH, Noseworthy JH. Nuclear aberrations in hair follicle cells of patients receiving cyclophosphamide. Arch Toxicol. 1990. 64: 116-121.   DOI   ScienceOn
35 English HF, Kyprianou N, Isaacs JT. Relationship between DNA fragmentation and apoptosis in the programmed cell death in the rat prostate following castration. Prostate. 1989. 15: 233 -250.   DOI   ScienceOn
36 Erdely A, Freshour G, Baylis C. Resistance to renal damage by chronic nitric oxide synthase inhibition in the Wistar-Furth rat. 2006. Am J Physiol Intergr Comp Physiol. 290(1): R66 -72.   DOI