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Am J Physiol Heart Circ Physiol 284: H2269-H2276, 2003. First published January 16, 2003; doi:10.1152/ajpheart.00774.2002
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Vol. 284, Issue 6, H2269-H2276, June 2003

Oxytocinergic regulation of cardiovascular function: studies in oxytocin-deficient mice

Lisete C. Michelini1, Marialuisa C. Marcelo2, Janet Amico3, and Mariana Morris2

1 Department of Physiology and Biophysics, Biomedical Sciences Institute, University of Sao Paulo, 05508-900, Sao Paulo, Brazil; 2 Department of Pharmacology and Toxicology, Wright State University School of Medicine, Dayton, Ohio 45401; and 3 Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

Oxytocin (OT) has been implicated in the cardiovascular responses to exercise, stress, and baroreflex adjustments. Studies were conducted to determine the effect of genetic manipulation of the OT gene on blood pressure (BP), heart rate (HR), and autonomic/baroreflex function. OT knockout (OTKO -/-) and control +/+ mice were prepared with chronic arterial catheters. OTKO -/- mice exhibited a mild hypotension (102 ± 3 vs. 110 ± 3 mmHg). Sympathetic and vagal tone were tested using beta 1-adrenergic and cholinergic blockade (atenolol and atropine). Magnitude of sympathetic and vagal tone to the heart and periphery was not significantly different between groups. However, there was an upward shift of sympathetic tone to higher HR values in OTKO -/- mice. This displacement combined with unchanged basal HR led to larger responses to cholinergic blockade (+77 ± 25 vs. +5 ± 15 beats/min, OTKO -/- vs. control +/+ group). There was also an increase in baroreflex gain (-13.1 ± 2.5 vs. -4.1 ± 1.2 beats · min-1 · mmHg-1, OTKO -/- vs. control +/+ group) over a smaller BP range. Results show that OTKO -/- mice are characterized by 1) hypotension, suggesting that OT is involved in tonic BP maintenance; 2) enhanced baroreflex gain over a small BP range, suggesting that OT extends the functional range of arterial baroreceptor reflex; and 3) shift in autonomic balance, indicating that OT reduces the sympathetic reserve.

heart rate; blood pressure; autonomic nervous system; peptides; genetic models; brain


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