1. ^*School of Physical Therapy, Chung Shan Medical University, Taichung, Taiwan
2. ^†First Department of Medicine, Asahikawa Medical College, Asahikawa, Japan
3. ^‡Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, New York

Correspondence: Gaspar A. Farkas, Department of Exercise and Nutrition Sciences, 405 Kimball Tower, University at Buffalo, 3435 Main Street, Buffalo, NY 14214-3079. E-mail: farkas@buffalo.edu

^**The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 19 April 2004; Accepted 20 December 2004.

Abstract

Objectives: The goal of our study was to determine whether altered adenosinergic mechanisms contribute to the depressed ventilatory response observed in obese Zucker rats.

Research Methods and Procedures: Eight lean and eight obese Zucker rats were studied at 7 to 8 weeks of age. Ventilation (V_E) during room air, during 5-minute hypercapnic (7% CO₂, balance O₂), and during 30-minute sustained hypoxic (10% O₂) exposures were sequentially measured by the barometric method on three separate occasions after the randomized blinded administration of equal volumes of either saline (control), 8-(p-sulfophenyl)-theophylline (8-PST, 7 mg/kg, peripheral adenosine antagonist), or aminophylline (AMPH, 15 mg/kg, peripheral and central adenosine antagonist).

Results: During room air and hypercapnic exposures, AMPH (but not 8-PST) significantly (p < 0.05) increased V_E in both lean and obese rats. During acute (2 minute) hypoxic exposure, 8-PST (but not AMPH) significantly depressed V_E in lean rats. In contrast, AMPH (but not 8-PST) selectively increased V_E in obese rats. During sustained (10 to 30 minutes) hypoxic exposure, neither AMPH nor 8-PST administration altered V_E in lean rats. In contrast, AMPH (but not 8-PST) selectively increased V_E during the late response in obese rats.

Discussion: Our findings indicate that obese rats possess altered adenosinergic modulation of ventilatory responses to acute and sustained hypoxia in two opposite ways. We conclude that the reduced hypoxic ventilatory response observed in obese Zucker rats is attributed to depressed adenosinergic peripheral excitatory mechanisms and to enhanced adenosinergic central depression mechanisms, both of which contribute to the blunted ventilatory response in obesity.