Differential cardiovascular responses to blockade of nNOS or iNOS in rostral ventrolateral medulla of the rat

被引:104
作者
Chan, SHH
Wang, LL
Wang, SH
Chan, JYH [1 ]
机构
[1] Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung 81346, Taiwan
[2] Natl Sun Yat Sen Univ, Ctr Neurosci, Kaohsiung 80424, Taiwan
关键词
nitric oxide; neuronal and inducible nitric oxide synthase; rostral ventrolateral medulla; systemic arterial pressure; heart rate; sympathetic vasomotor outflow;
D O I
10.1038/sj.bjp.0704105
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 We investigated the contribution of neuronal or inducible nitric oxide synthase (nNOS or iNOS) at the rostral ventrolateral medulla (RVLM) to central cardiovascular regulation by endogenous nitric oxide (NO), using Sprague-Dawley rats anaesthetized and maintained with propofol. 2 Microinjection bilaterally into the RVLM of a NO trapping agent, carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxy-1-3-oxide (10, 50 or 100 nmoles) resulted in significant hypotension and bradycardia. 3 Similar application of a selective antagonist of nNOS, 7-nitroindazole (1, 2.5 or 5 pmoles), or selective antagonists of iNOS, aminoguanidine (125, 250 or 500 pmoles), N-6-(1-iminoethyl)-L-lysine (250 pmoles) or S-methylisothiourea (250 pmoles), induced respectively a reduction or on enhancement in systemic arterial pressure, heart rate and power density of the vasomotor components in the spectrum of arterial blood pressure signals, the experimental index for sympathetic neurogenic vasomotor tone. 4 Both hypotension and bradycardia induced by the NO precursor, L-arginine (100 nmoles), were significantly blunted when aminoguanidine (250 pmoles) was co-microinjected bilaterally into the RVLM. On the other hand, co-administered 7-nitroindazole (2.5 pmoles) was ineffective. 5 Whereas low doses of S-nitro-N-acetylpenicillamine (0.25 or 0.5 nmoles) elicited hypertension and tachycardia, high doses of this non-nitrate NO donor (5 nmoles) induced hypotension and bradycardia. 6 Reverse transcription-polymerase chain reaction analysis revealed that both iNOS and nNOS mRNA were expressed in the ventrolateral medulla. 7 We conclude that the prevalence of nNOS over iNOS activity at the RVLM and the associated dominance of sympathoexcitation over sympathoinhibition may underlie the maintenance of sympathetic vasomotor outflow and stable systemic arterial pressure by the endogenous NO.
引用
收藏
页码:606 / 614
页数:9
相关论文
共 51 条
[1]   Formation of guanidinosuccinic acid, a stable nitric oxide mimic, from argininosuccinic acid and nitric oxide-derived free radicals [J].
Aoyagi, K ;
Akiyama, K ;
Shahrzad, S ;
Tomida, C ;
Hirayama, A ;
Nagase, S ;
Takemura, K ;
Koyama, A ;
Ohba, S ;
Narita, M .
FREE RADICAL RESEARCH, 1999, 31 (01) :59-65
[2]   MICROGLIAL-PRODUCED NITRIC-OXIDE AND REACTIVE NITROGEN-OXIDES MEDIATE NEURONAL CELL-DEATH [J].
BOJE, KM ;
ARORA, PK .
BRAIN RESEARCH, 1992, 587 (02) :250-256
[3]   LOCALIZATION OF NITRIC-OXIDE SYNTHASE INDICATING A NEURAL ROLE FOR NITRIC-OXIDE [J].
BREDT, DS ;
HWANG, PM ;
SNYDER, SH .
NATURE, 1990, 347 (6295) :768-770
[4]   ISOLATION OF NITRIC-OXIDE SYNTHETASE, A CALMODULIN-REQUIRING ENZYME [J].
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (02) :682-685
[5]   Differential roles of iNOS and nNOS at rostral ventrolateral medulla during experimental endotoxemia in the rat [J].
Chan, JYH ;
Wang, SH ;
Chan, SHH .
SHOCK, 2001, 15 (01) :65-72
[6]   SUPPRESSION OF ADJUVANT-INDUCED ARTHRITIS BY SELECTIVE-INHIBITION OF INDUCIBLE NITRIC-OXIDE SYNTHASE [J].
CONNOR, JR ;
MANNING, PT ;
SETTLE, SL ;
MOORE, WM ;
JEROME, GM ;
WEBBER, RK ;
TJOENG, FS ;
CURRIE, MG .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1995, 273 (1-2) :15-24
[7]   THE SUBRETROFACIAL VASOMOTOR NUCLEUS - ANATOMICAL, CHEMICAL AND PHARMACOLOGICAL PROPERTIES AND ROLE IN CARDIOVASCULAR REGULATION [J].
DAMPNEY, RAL .
PROGRESS IN NEUROBIOLOGY, 1994, 42 (02) :197-227
[8]   NITRIC-OXIDE SYNTHASE IMMUNOREACTIVITY IN RAT PONTINE MEDULLARY NEURONS [J].
DUN, NJ ;
DUN, SL ;
FORSTERMANN, U .
NEUROSCIENCE, 1994, 59 (02) :429-445
[9]  
Forstermann U, 1995, Adv Pharmacol, V34, P171
[10]   CYTOKINE-INDUCED SYNTHESIS OF NITROGEN-OXIDES IN MACROPHAGES - A PROTECTIVE HOST RESPONSE TO LEISHMANIA AND OTHER INTRACELLULAR PATHOGENS [J].
GREEN, SJ ;
NACY, CA ;
MELTZER, MS .
JOURNAL OF LEUKOCYTE BIOLOGY, 1991, 50 (01) :93-103