Alterations to the nitric oxide pathway in the spontaneously hypertensive rat

被引:80
作者
Nava, E
Farré, AL
Moreno, C
Casado, S
Moreau, P
Cosentino, F
Lüscher, TF
机构
[1] Univ Zurich Hosp, CH-8091 Zurich, Switzerland
[2] Univ Murcia, Sch Med, Dept Physiol, Murcia, Spain
[3] Fdn Jimenez Diaz, Lab Nephrol & Hypertens, E-28040 Madrid, Spain
关键词
spontaneous hypertension; nitric oxide synthase; nitric oxide; nitrate; cyclic GMP;
D O I
10.1097/00004872-199816050-00008
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Objectives To examine the role of nitric oxide in the cardiovascular system in spontaneous hypertension. In particular, we wanted to know whether the production of nitric oxide in the cardiovascular system of the spontaneously hypertensive rat is different from that of the normotensive Wistar-Kyoto rat and whether nitric oxide is biologically effective in this system. Design We studied various aspects of the L-arginine-nitric oxide pathway in the cardiovascular system of spontaneously hypertensive rats and Wistar-Kyoto rats. Methods To address the first objective we analysed the expression of endothelial nitric oxide synthase in the heart by Western blotting and the activity of constitutive nitric oxide synthase in resistance microvessels obtained from the mesenterium, both from spontaneously hypertensive rats and Wistar-Kyoto rats aged 14-18 weeks. We also analysed the concentration of the oxidative product of nitric oxide, nitrate, in plasma from these rats. To address the second objective, that is, to assess the bioactivity of nitric oxide, we studied the accumulation in tissue of cyclic guanosine 3',5'-monophosphate (GMP), as well as the acute and chronic effects of withdrawing the nitric oxide vasodilatory tone with the inhibitor of nitric oxide synthesis N-G-nitro-L-arginine methyl ester on Wistar-Kyoto rats and spontaneously hypertensive rats. Results We found that the expression of endothelial nitric oxide synthase in the heart, the activity of constitutive nitric oxide synthase in resistance microvessels and the concentration of nitrate in plasma were all significantly higher in the spontaneously hypertensive rats. In contrast, neither cyclic GMP levels nor the effects of N-G-nitro-L-arginine methyl ester were greater in the spontaneously hypertensive rat than they were in the Wistar-Kyoto rat. Conclusions The nitric oxide pathway is upregulated in the resistance circulation and the heart of the spontaneously hypertensive rat by a mechanism involving induction of the constitutive nitric oxide synthase and overproduction of nitric oxide. However, nitric oxide is not sufficiently bioactive to stimulate the formation of cyclic GMP and to maintain an adequate nitric oxide-dependent vasodilatory tone. (C) 1998 Lippincott-Raven Publishers.
引用
收藏
页码:609 / 615
页数:7
相关论文
共 19 条
[1]   DETERMINANTS OF AORTIC CYCLIC GUANOSINE-MONOPHOSPHATE IN HYPERTENSION INDUCED BY CHRONIC INHIBITION OF NITRIC-OXIDE SYNTHASE [J].
ARNAL, JF ;
WARIN, L ;
MICHEL, JB .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (02) :647-652
[2]   BLOOD HYPERVISCOSITY IN SPONTANEOUSLY HYPERTENSIVE RATS [J].
DECLERCK, F ;
BEERENS, M ;
VANGORP, L ;
XHONNEUX, R .
THROMBOSIS RESEARCH, 1980, 18 (1-2) :291-295
[3]   IMPAIRED ENDOTHELIUM-DEPENDENT RELAXATIONS IN HYPERTENSIVE RESISTANCE ARTERIES INVOLVE CYCLOOXYGENASE PATHWAY [J].
DIEDERICH, D ;
YANG, ZH ;
BUHLER, FR ;
LUSCHER, TF .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (02) :H445-H451
[4]   Endothelial cells inhibit NO generation by vascular smooth muscle cells - Role of transforming growth factor-beta [J].
Farre, AL ;
Mosquera, JR ;
deMiguel, LS ;
Millas, I ;
deFrutos, T ;
Monton, M ;
Sierra, MP ;
Riesco, A ;
Casado, S .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1996, 16 (10) :1263-1268
[5]   BIOTRANSFORMATION OF ORGANIC NITRATES TO NITRIC-OXIDE BY VASCULAR SMOOTH-MUSCLE AND ENDOTHELIAL-CELLS [J].
FEELISCH, M ;
KELM, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 180 (01) :286-293
[6]   ENDOTHELIUM-DEPENDENT CONTRACTIONS TO ACETYLCHOLINE IN THE AORTA OF THE SPONTANEOUSLY HYPERTENSIVE RAT [J].
LUSCHER, TF ;
VANHOUTTE, PM .
HYPERTENSION, 1986, 8 (04) :344-348
[7]   CHRONIC TREATMENT WITH POLYETHYLENE-GLYCOLATED SUPEROXIDE-DISMUTASE PARTIALLY RESTORES ENDOTHELIUM-DEPENDENT VASCULAR RELAXATIONS IN CHOLESTEROL-FED RABBITS [J].
MUGGE, A ;
ELWELL, JH ;
PETERSON, TE ;
HOFMEYER, TG ;
HEISTAD, DD ;
HARRISON, DG .
CIRCULATION RESEARCH, 1991, 69 (05) :1293-1300
[8]   STRUCTURE AND FUNCTION OF SMALL ARTERIES [J].
MULVANY, MJ ;
AALKJAER, C .
PHYSIOLOGICAL REVIEWS, 1990, 70 (04) :921-961
[9]   DOES SUPEROXIDE UNDERLIE THE PATHOGENESIS OF HYPERTENSION [J].
NAKAZONO, K ;
WATANABE, N ;
MATSUNO, K ;
SASAKI, J ;
SATO, T ;
INOUE, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (22) :10045-10048
[10]   INCREASED ACTIVITY OF CONSTITUTIVE NITRIC-OXIDE SYNTHASE IN CARDIAC ENDOTHELIUM IN SPONTANEOUS HYPERTENSION [J].
NAVA, E ;
NOLL, G ;
LUSCHER, TF .
CIRCULATION, 1995, 91 (09) :2310-2313