This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lewis, S. J. Articles by Brody, M. J. Search for Related Content PubMed PubMed Citation Articles by Lewis, S. J. Articles by Brody, M. J.

Hypertension, Vol 13, 759-765, Copyright © 1989 by American Heart Association

ARTICLES

Cardiovascular effects of the N-methyl-D-aspartate receptor antagonist MK-801 in conscious rats

SJ Lewis, C Barres, HJ Jacob, H Ohta and MJ Brody
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242.

Evidence from microinjection studies in anesthetized rats suggests that central excitatory amino acid pathways using N-methyl-D-aspartate receptors are involved in the regulation of the cardiovascular system. To test the hypothesis that these pathways are tonically involved in the maintenance of or the baroreceptor reflex regulation of cardiovascular function, we have examined the effects of intravenous injection of the centrally acting, noncompetitive N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine (MK-801), on the mean arterial pressure, heart rate, renal sympathetic nerve activity, and behavior of conscious, freely moving sham-operated and sinoaortic baroreceptor- denervated rats. Administration of MK-801 produced, within 5 minutes, dose-dependent elevations in mean arterial pressure, heart rate, and renal sympathetic nerve activity that were sustained for 0.5 to 2.5 hours. For an equivalent dose, MK-801 produced approximately twice the peak changes in mean arterial pressure and heart rate in the sinoaortic baroreceptor-denervated rats than in the sham-operated rats. Pretreatment results were as follows: 1) The ganglion blocker chlorisondamine markedly attenuated the hypertension and tachycardia in the sham-operated and sinoaortic baroreceptor-denervated rats, 2) pretreatment with the alpha 1-adrenergic receptor antagonist prazosin virtually abolished the hypertension, and 3) the beta 1-adrenergic receptor antagonist atenolol markedly reduced the tachycardia. MK-801 also produced stereotypic behaviors and ataxia in the sham-operated and sinoaortic baroreceptor-denervated rats; however, qualitatively and quantitatively similar changes in behavior were induced in the latter by doses approximately five time lower than required in sham operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				E. J. Whalen, T. G. Beltz, S. J. Lewis, and A. K. Johnson AV3V lesions attenuate the cardiovascular responses produced by blood-borne excitatory amino acid analogs Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1409 - H1415. [Abstract] [Full Text] [PDF]

				P. J. Ohtake, J. E. Torres, Y. M. Gozal, G. R. Graff, and D. Gozal NMDA receptors mediate peripheral chemoreceptor afferent input in the conscious rat J Appl Physiol, March 1, 1998; 84(3): 853 - 861. [Abstract] [Full Text] [PDF]

				M. M. Knuepfer and Q. Gan Effects of Proposed Treatments for Cocaine Addiction on Hemodynamic Responsiveness to Cocaine in Conscious Rats J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 592 - 603. [Abstract] [Full Text]

				D. S. Feldman and J. J. Buccafusco Spinal Muscarinic, Glutamatergic and GABAergic Receptor Systems in Cardiovascular Regulation J. Pharmacol. Exp. Ther., April 1, 1997; 281(1): 274 - 283. [Abstract] [Full Text]