Biomaterial Database

Neuronal norepinephrine responses of the rostral ventrolateral medulla and nucleus tractus solitarius neurons distinguish the I1- from the alpha2-receptor-mediated hypotension in conscious SHRs. 2005

Guichu Li, and Xu Wang, and Abdel A Abdel-Rahman

Department of Pharmacology, Brody School of Medicine, Greenville, North Carolina 27858-4353, USA.

We tested the hypothesis that the I1 receptor mediates the reduction in rostral ventrolateral medulla (RVLM) neuronal norepinephrine (NE; index of sympathetic activity) that leads to hypotension independent of other brainstem areas or the alpha2-adrenergic receptor. To this end, we developed a model that permitted measurement of real-time changes in neuronal NE in the RVLM or nucleus tractus solitarius (NTS) along with blood pressure and heart rate in the conscious SHR in response to localized microinjections of selective I1 (rilmenidine) or alpha2-adrenergic (alpha-methylnorepinephrine; alpha-MNE) agonist versus the mixed I1/alpha2 agonist clonidine. To further support the hypothesis, we investigated the effects of localized selective alpha2- (SK&F86466) or I1 (efaroxan) blockade on the reductions in neuronal NE and blood pressure elicited by intra-RVLM rilmenidine. In the latter experiment, changes in RVLM neuronal c-Fos (another marker of sympathetic neural activity) were also investigated. Intra-RVLM rilmenidine (40 nmol) or clonidine (1 nmol) similarly reduced RVLM NE and blood pressure; these responses were approximately 2-fold greater than those elicited by the pure alpha2-adrenergic agonist alpha-MNE (10 nmol). By contrast, intra-NTS rilmenidine or clonidine had no effect on NTS NE or blood pressure versus significant reductions in both parameters by alpha-MNE. Intra-RVLM rilmenidine decreased c-Fos expression, and these responses were abolished by efaroxan but not by SK&F 86466. These findings suggest: (1) in the RVLM, I1-receptor signaling suppresses cardiovascular neuron activity, which leads to lowering of blood pressure; (2) although the alpha2-adrenergic receptor in the RVLM serves a similar role, it does not exert a tonic neuronal inhibitory effect and is not essential, as a downstream signaling entity, for the I1-evoked neurobiological effects in the brainstem. The potential confounding effects of anesthetics on the I1 and/or alpha2 receptor-mediated neuronal and cardiovascular responses were circumvented in the present study.

UI	MeSH Term	Description	Entries
D007022	Hypotension	Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.	Blood Pressure, Low,Hypotension, Vascular,Low Blood Pressure,Vascular Hypotension
D007093	Imidazoles	Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007375	Interleukin-1	A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.	IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008297	Male		Males
D008771	Nordefrin	A norepinephrine derivative used as a vasoconstrictor agent.	Methylnorepinephrine,3,4-Dihydroxynorephedrine,4-(2-Amino-1-hydroxypropyl)-1,2-benzenediol,4-(2-Amino-1-hydroxypropyl)-1,2-benzenediol Hydrochloride, (R,R)-(+,-)-Isomer,4-(2-Amino-1-hydroxypropyl)-1,2-benzenediol Hydrochloride, (R,S)-(+-)-Isomer,4-(2-Amino-1-hydroxypropyl)-1,2-benzenediol Tartrate, (R,R), (R,R)-Isomer,4-(2-Amino-1-hydroxypropyl)-1,2-benzenediol Tartrate, (R,S), (R,R)-Isomer,4-(2-Amino-1-hydroxypropyl)-1,2-benzenediol, (R,R)-Isomer,4-(2-Amino-1-hydroxypropyl)-1,2-benzenediol, (R,S)-Isomer,Cobefrine,Corbadrine,Levonordefrin,Neo-Cobefrin,Nordefrin Hydrochloride,Nordefrin Hydrochloride, (R,R)-(+,-)-Isomer,Nordefrin Hydrochloride, (R,S)-(+,-)-Isomer,Nordefrin Tartrate, (R,R), (R,R) Isomer,Nordefrin Tartrate, (R,S), (R,R) Isomer,Nordefrin, (R,R)-Isomer,Nordefrin, (R,S)-Isomer,Norephrine,alpha-Methylnoradrenaline,alpha-Methylnorepinephrine,3,4 Dihydroxynorephedrine,Hydrochloride, Nordefrin,Neo Cobefrin,NeoCobefrin,alpha Methylnoradrenaline,alpha Methylnorepinephrine
D009043	Motor Activity	Body movements of a human or an animal as a behavioral phenomenon.	Activities, Motor,Activity, Motor,Motor Activities
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010080	Oxazoles	Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.	Oxazole,1,3-Oxazolium-5-Oxides,Munchnones,1,3 Oxazolium 5 Oxides
D011918	Rats, Inbred SHR	A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke.	Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats