Abstract
Activation of the sympathetic nervous system and renin-angiotensin system has been suggested to contribute to the hypertension caused by chronic nitric oxide synthase inhibition. The aim of the present study was to determine whether angiotensin within the nucleus tractus solitarii (NTS) plays a role in activation of the sympathetic nervous system in this model. Rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg. kg(-1). d(-1) in drinking water) for 2 weeks. Experiments were performed on anesthetized rats with denervated arterial and cardiopulmonary baroreceptors. Arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were measured. Microinjection of an angiotensin II type 1 (AT(1)) receptor antagonist (CV11974) or an angiotensin II type 2 (AT(2)) receptor antagonist (PD123319) into the depressor region within the NTS (identified by prior injection of L-glutamate) was performed. Microinjection of CV11974, but not of PD123319, produced greater decreases in arterial pressure, heart rate, and RSNA in L-NAME-treated rats than in control rats. The administration of hexamethonium resulted in a larger fall in arterial pressure in L-NAME-treated rats than in control rats. The ACE mRNA level in the brain stem was greater in L-NAME-treated rats than in control rats. These results suggest that increased sympathetic nerve activity plays a role in hypertension caused by chronic nitric oxide synthase inhibition and that activation of the renin-angiotensin system in the NTS is involved at least in part in this increased sympathetic nerve activity via AT(1) receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin Receptor Antagonists
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Angiotensins / physiology*
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Animals
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Antihypertensive Agents / pharmacology
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Benzimidazoles / pharmacology
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Biphenyl Compounds
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Blood Pressure / drug effects
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Brain Stem / drug effects
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Brain Stem / metabolism
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Cerebral Ventricles / drug effects
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Cerebral Ventricles / physiopathology
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation / drug effects
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Heart Rate / drug effects
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Hexamethonium / pharmacology
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Hypertension / enzymology
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Hypertension / physiopathology*
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Imidazoles / pharmacology
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Kidney / innervation
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Kidney / physiopathology
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Male
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NG-Nitroarginine Methyl Ester / pharmacology
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase Type I
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Peptidyl-Dipeptidase A / genetics
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Pyridines / pharmacology
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred WKY
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Receptor, Angiotensin, Type 1
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Receptor, Angiotensin, Type 2
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Receptors, Angiotensin / genetics
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Solitary Nucleus / drug effects
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Solitary Nucleus / physiopathology*
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Sympathetic Nervous System / drug effects
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Sympathetic Nervous System / physiopathology
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Tetrazoles / pharmacology
Substances
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Angiotensin Receptor Antagonists
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Angiotensins
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Antihypertensive Agents
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Benzimidazoles
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Biphenyl Compounds
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Enzyme Inhibitors
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Imidazoles
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Pyridines
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RNA, Messenger
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Receptor, Angiotensin, Type 1
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Receptor, Angiotensin, Type 2
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Receptors, Angiotensin
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Tetrazoles
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PD 123319
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Hexamethonium
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nos1 protein, rat
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Peptidyl-Dipeptidase A
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candesartan
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NG-Nitroarginine Methyl Ester