Published Online
on September 12, 2005

A more recent version of this article appeared on October 1, 2005

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Submitted on April 28, 2005
Revised on May 26, 2005

Hypertension and Exercise Training Differentially Affect Oxytocin and Oxytocin Receptor Expression in the Brain

Adriano S. Martins; Alessandra Crescenzi; Javier E. Stern; Silvana Bordin; and Lisete C. Michelini^*

From the Department of Physiology and Biophysics (A.S.M., A.C., S.B., L.C.M.), Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil, and the Department of Psychiatry (J.E.S.), University of Cincinnati, Cincinnati, Ohio.

^* To whom correspondence should be addressed. E-mail: Michelin{at}usp.br.

Abstract--We have previously shown that exercise training activates nucleus tractus solitarii (NTS) oxytocinergic projections, resulting in blunted exercise tachycardia. The objective of this study was to determine the effects of hypertension and training on oxytocin (OT) and OT receptor expression in the hypothalamic paraventricular nucleus (PVN) and projection areas (dorsal brain stem [DBS]). Male, normotensive, Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were trained (55% maximal exercise capacity, 3 months) or kept sedentary, and pressure was measured weekly. DBS sections were processed for immunohistochemistry (polyclonal guinea pig anti-OT) or in situ hybridization for OT and OT receptor (³⁵S-oligonucleotide probes). Other groups of rats had brains removed and frozen to isolate the DBS and PVN; samples were processed for OT and OT receptor cDNA reverse transcription-polymerase chain reaction amplification with -actin as the housekeeping gene. Training was equally effective in improving running distance in both groups, with pressure reduction only in SHR (-10%, P<0.05). In trained WKY, baseline bradycardia (P<0.05) occurred simultaneously with increased NTS OT immunostaining and mRNA expression (+3.5-fold), without any change in OT receptor mRNA expression. PVN OT mRNA and DBS OT receptor mRNA expressions were significantly lower in SHR versus WKY (-39% and -56%, respectively). Training did not alter DBS OT receptor density in the SHR group but increased OT mRNA in both PVN and DBS areas (+78% and +45%, respectively). Our results show a marked hypertension-induced reduction in OT receptor mRNA expression, not altered by training. In contrast, training increased OT mRNA expression in sedentary and hypertensive rats, which may facilitate training-induced cardiac performance.

Key words: hypothalamus • exercise • rats, spontaneously hypertensive • neurotransmitter • genetics • autonomic nervous system • immunohistochemistry

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