PMID- 12235252
OWN - NLM
STAT- MEDLINE
DCOM- 20021021
LR  - 20181130
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 303
IP  - 1
DP  - 2002 Oct
TI  - The hypotensive action of rilmenidine is dependent on functional 
      N-methyl-D-aspartate receptor in the rostral ventrolateral medulla of conscious 
      spontaneously hypertensive rats.
PG  - 204-10
AB  - Rilmenidine is a second-generation centrally acting antihypertensive drug that 
      acts mainly through the activation of the imidazoline (I(1)) receptor in the 
      rostral ventrolateral medulla (RVLM). To investigate the contribution of the 
      N-methyl-D-aspartate receptor (NMDAR) to the hypotensive action of rilmenidine, 
      experiments were undertaken in conscious male spontaneously hypertensive rats 
      (SHRs). Microinjection of cumulative doses of rilmenidine (10, 20, and 40 nmol) 
      at 10- to 15-min intervals, into the RVLM elicited dose-dependent hypotensive and 
      bradycardic response. Pretreatment with intra-RVLM 2-amino-5-phosphonopentanoic 
      acid (AP5) (2 nmol), a selective NMDAR antagonist, not only abolished the 
      hypotensive response elicited by intra-RVLM rilmenidine (40 nmol) but also 
      converted it to a pressor response (-24 +/- 1 versus 17 +/- 7 mm Hg; P < 0.05) 
      and significantly attenuated the bradycardic response (-72 +/- 18 versus -24 +/- 
      20 bpm; P < 0.05). The blood pressure response to intra-RVLM N-methyl-D-aspartate 
      (NMDA) depended on the dose applied. Whereas intra-RVLM NMDA (>20 pmol) produced 
      the expected pressor response, a lower dose (10 pmol) reduced mean arterial 
      pressure (MAP) (-14 +/- 3 mm Hg) and heart rate (-21 +/- 12 bpm). The divergent 
      MAP responses were attenuated by intra-RVLM AP5 (2 nmol), which implicates the 
      NMDAR in the pressor as well as the depressor response. The present findings 
      suggest that the NMDAR in the RVLM of the SHR 1) exerts dual effects on blood 
      pressure, with the response type depending on the level of NMDAR activation, and 
      2) plays a pivotal role in the hypotension mediated by I(1) receptor activation 
      in the RVLM.
FAU - Zhang, Jian
AU  - Zhang J
AD  - Department of Pharmacology, The Brody School of Medicine at East Carolina 
      University, Greenville, North Carolina 27858, USA.
FAU - Abdel-Rahman, Abdel A
AU  - Abdel-Rahman AA
LA  - eng
GR  - R01 AA007839/AA/NIAAA NIH HHS/United States
GR  - AA 07839/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Oxazoles)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - P67IM25ID8 (Rilmenidine)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/pharmacology
MH  - Animals
MH  - Antihypertensive Agents/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Hemodynamics/*drug effects
MH  - Hypertension/drug therapy/*physiopathology
MH  - Male
MH  - Medulla Oblongata/drug effects/physiology/*physiopathology
MH  - Microinjections
MH  - N-Methylaspartate/pharmacology
MH  - Oxazoles/administration & dosage/*pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/*physiology
MH  - Rilmenidine
EDAT- 2002/09/18 10:00
MHDA- 2002/10/22 04:00
CRDT- 2002/09/18 10:00
PHST- 2002/09/18 10:00 [pubmed]
PHST- 2002/10/22 04:00 [medline]
PHST- 2002/09/18 10:00 [entrez]
AID - 10.1124/jpet.102.037333 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2002 Oct;303(1):204-10. doi: 10.1124/jpet.102.037333.