HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/R1149    most recent 90485.2008v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Wang, G. Articles by Pierce, J. P. Search for Related Content PubMed PubMed Citation Articles by Wang, G. Articles by Pierce, J. P.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Sex differences in angiotensin signaling in bulbospinal neurons in the rat rostral ventrolateral medulla

¹Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York; ²Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York; ³Department of Pharmacology, University of Mississippi School of Pharmacy, University of Mississippi, University, Mississippi; and ⁴Division of Pharmacology and Toxicology, University of Texas, Austin, Austin Texas

Submitted 9 June 2008 ; accepted in final form 29 July 2008

Sex differences may play a significant role in determining the risk of hypertension. Bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are involved in the tonic regulation of arterial pressure and participate in the central mechanisms of hypertension. Angiotensin II (ANG II) acting on angiotensin type 1 (AT₁) receptors in RVLM neurons is implicated in the development of hypertension by activating NADPH oxidase and producing reactive oxygen species (ROS). Therefore, we analyzed RVLM bulbospinal neurons to determine whether there are sex differences in: 1) immunolabeling for AT₁ receptors and the key NADPH oxidase subunit p47 using dual-label immunoelectron microscopy, and 2) the effects of ANG II on ROS production and Ca²⁺ currents using, respectively, hydroethidine fluoromicrography and patch-clamping. In tyrosine hydroxylase-positive RVLM neurons, female rats displayed significantly more AT₁ receptor immunoreactivity and less p47 immunoreactivity than male rats (P < 0.05). Although ANG II (100 nM) induced comparable ROS production in dissociated RVLM bulbospinal neurons of female and male rats (P > 0.05), an effect mediated by AT₁ receptors and NADPH oxidase, it triggered significantly larger dihydropyridine-sensitive long-lasting (L-type) Ca²⁺ currents in female RVLM neurons (P < 0.05). These observations suggest that an increase in AT₁ receptors in female RVLM neurons is counterbalanced by a reduction in p47 levels, such that ANG II-induced ROS production does not differ between females and males. Since the Ca²⁺ current activator Bay K 8644 induced larger Ca²⁺ currents in females than in male RVLM neurons, increased ANG II-induced L-type Ca²⁺ currents in females may result from sex differences in calcium channel densities or dynamics.

C1 neurons; reactive oxygen species; NADPH oxidase; calcium channel; estrogen

This article has been cited by other articles:

				H. Girouard, G. Wang, E. F. Gallo, J. Anrather, P. Zhou, V. M. Pickel, and C. Iadecola NMDA Receptor Activation Increases Free Radical Production through Nitric Oxide and NOX2 J. Neurosci., February 25, 2009; 29(8): 2545 - 2552. [Abstract] [Full Text] [PDF]

				R. A. L. Dampney Is the RVLM a key site for sex-related differences in blood pressure regulation? Focus on "Sex differences in angiotensin signaling in bulbospinal neurons in the rat rostral ventrolateral medulla," by Wang et al. Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1147 - R1148. [Full Text] [PDF]