This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Makaritsis, K. P. Articles by Gavras, H. Search for Related Content PubMed PubMed Citation Articles by Makaritsis, K. P. Articles by Gavras, H. Related Collections Genetically altered mice Autonomic, reflex, and neurohumoral control of circulation Receptor pharmacology

(Hypertension. 2000;35:609.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Role of ₂-Adrenergic Receptor Subtypes in the Acute Hypertensive Response to Hypertonic Saline Infusion in Anephric Mice

Konstantinos P. Makaritsis; Conrado Johns; Irene Gavras; Haralambos Gavras

From the Hypertension and Atherosclerosis Section of the Department of Medicine, Boston University School of Medicine, Boston, Mass.

Correspondence to Haralambos Gavras, MD, Hypertension and Atherosclerosis Section, Boston University School of Medicine, 715 Albany St, Boston, MA 02118. E-mail hgavras{at}bu.edu

Abstract—Experimental evidence suggests that the acute hypertensive response induced in anephric animals by infusion of a hypertonic saline solution is mediated by disinhibition of the presynaptic sympathoinhibitory ₂-adrenergic receptors (₂-AR) of the central nervous system. The purpose of the present experiments was to dissect the role of the 3 distinct ₂-AR subtypes (_2A-, _2B, - and _2C-AR) in this response. Groups of genetically engineered mice deficient in each one of these ₂-AR subtype genes were submitted to bilateral nephrectomy followed by a 0.4-mL infusion of 4% saline over a 2-hour period, with constant direct blood pressure (BP) monitoring. The _2A-AR–deficient and _2C-AR–deficient mice responded with significant BP elevations (by 11.8±2.5 and 16.7±1.7 mm Hg, respectively), and so did their wild-type counterparts (17.8±2.5 and 11.8±2.0 mm Hg, respectively) and the wild-type _2B +/+ (13.1±2.4 mm Hg). However, the _2B-AR–deficient mice were unable to raise their BP and had a slightly lowered BP (by -3.0±4.0 mm Hg) at the end of the infusion period. All 6 groups exhibited elevated plasma norepinephrine levels ranging between 0.8 and 1.8 ng/mL at the end of the infusion. In all cases, the ₂-AR–deficient groups tended to have higher norepinephrine levels than their wild-type counterparts. Surprisingly, this difference was significant only in the _2B-AR–deficient mice, which, despite the elevated norepinephrine, were unable to raise their BP. The data suggest that a full complement of the _2B-AR is needed to mediate the hypertensive response to acute saline load, even though its absence does not prevent the release of norepinephrine under these conditions.

Key Words: receptors • genes • hypertension, experimental

This article has been cited by other articles:

				M. Kumagai, T. Horiguchi, T. Nishikawa, Y. Masaki, and Y. Tobe Intravenous Dexmedetomidine Decreases Lung Permeability Induced by Intracranial Hypertension in Rats Anesth. Analg., August 1, 2008; 107(2): 643 - 647. [Abstract] [Full Text] [PDF]

				J. Tank, J. Jordan, A. Diedrich, M. Obst, R. Plehm, F. C. Luft, and V. Gross Clonidine Improves Spontaneous Baroreflex Sensitivity in Conscious Mice Through Parasympathetic Activation Hypertension, May 1, 2004; 43(5): 1042 - 1047. [Abstract] [Full Text] [PDF]

				O. Madsen, D. Willemsen, B. M. Ursing, U. Arnason, and W. W. de Jong Molecular Evolution of the Mammalian Alpha 2B Adrenergic Receptor Mol. Biol. Evol., December 1, 2002; 19(12): 2150 - 2160. [Abstract] [Full Text] [PDF]

				C. Plut, C. Ribiere, Y. Giudicelli, and J.-P. Dausse Gender Differences in Hypothalamic Tyrosine Hydroxylase and alpha 2-Adrenoceptor Subtype Gene Expression in Cafeteria Diet-Induced Hypertension and Consequences of Neonatal Androgenization J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 525 - 531. [Abstract] [Full Text] [PDF]

				M. Philipp, M. Brede, and L. Hein Physiological significance of alpha 2-adrenergic receptor subtype diversity: one receptor is not enough Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2002; 283(2): R287 - R295. [Abstract] [Full Text] [PDF]

				B. J. A. Janssen and J. F. M. Smits Autonomic control of blood pressure in mice: basic physiology and effects of genetic modification Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1545 - R1564. [Abstract] [Full Text] [PDF]

				M. Khalid, Y. Giudicelli, and J.-P. Dausse An Up-Regulation of Renal alpha 2A-Adrenoceptors Is Associated with Resistance to Salt-Induced Hypertension in Sabra Rats J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 928 - 933. [Abstract] [Full Text] [PDF]

				E. Kintsurashvili, I. Gavras, C. Johns, and H. Gavras Effects of Antisense Oligodeoxynucleotide Targeting of the {alpha}2B-Adrenergic Receptor Messenger RNA in the Central Nervous System Hypertension, November 1, 2001; 38(5): 1075 - 1080. [Abstract] [Full Text] [PDF]