Enhanced vascular neuronal nitric-oxide synthase-derived nitric-oxide production underlies the pressor response caused by peripheral N-methyl-D-aspartate receptor activation in conscious rats.

The Journal of Pharmacology and Experimental Therapeutics
Marie A McGee, Abdel A Abdel-Rahman

Abstract

Although the N-methyl-D-aspartate (NMDA) receptor (NMDAR) obligatory unit NMDAR1 is expressed in the vasculature and myocardium, the impact of peripheral NMDAR activation on blood pressure (BP) has received little attention. We demonstrate, for the first time, dose-related pressor responses elicited by systemic NMDA (125, 250, 500, and 1000 μg/kg) in conscious rats. The pressor response was peripheral NMDAR-mediated because: 1) it persisted after ganglion blockade (hexamethonium; 5 mg/kg i.v.); 2) it was attenuated by the selective NMDAR blocker DL-2-amino-5-phosphonopentanoic acid (5 mg/kg, i.v.) or the glycine/NMDAR antagonist R-(+)-3-amino-1-hydroxypyrrolid-2-one [R-(+)-HA-966; 10 mg/kg i.v.]; and 3) NMDA (1.25-10 mM) increased contractile force of rat aorta in vitro. It is noteworthy that ex vivo studies revealed enhanced nitric oxide (NO) and reactive oxygen species (ROS) generation in vascular tissues collected at the peak of the NMDAR-mediated pressor response. Pharmacological, ex vivo, and in vitro findings demonstrated attenuation of the NMDAR-mediated increases in BP and vascular NO and ROS by the nonselective NO synthase (NOS) inhibitor N(ω)-nitro-L-arginine methyl ester hydrochloride (10 mg/kg i.v.) or the neuronal ...Continue Reading

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Citations

Dec 17, 2014·Expert Opinion on Therapeutic Targets·Milica Bozic, José M Valdivielso
Dec 18, 2013·Journal of Cardiovascular Pharmacology·Marie A McGee, Abdel A Abdel-Rahman
Aug 2, 2017·Canadian Journal of Physiology and Pharmacology·Ivan SrejovicVladimir Jakovljevic
Feb 10, 2017·The Journal of Pharmacology and Experimental Therapeutics·Mohamed A Fouda, Abdel A Abdel-Rahman
Dec 26, 2013·American Journal of Physiology. Endocrinology and Metabolism·Mahmoud M El-Mas, Abdel A Abdel-Rahman
Jan 17, 2014·The Journal of Pharmacology and Experimental Therapeutics·Anusha Penumarti, Abdel A Abdel-Rahman
Nov 7, 2019·Alcoholism, Clinical and Experimental Research·Fanrong Yao, Abdel A Abdel-Rahman
Apr 6, 2016·Journal of Cardiovascular Pharmacology·Marie A McGee, Abdel A Abdel-Rahman
Jul 19, 2020·Biomolecules·José M ValdivielsoMilica Bozic
Aug 28, 2021·Frontiers in Psychiatry·Amir MeftahJoshua T Kantrowitz

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