Effect of Systemic Administration of the Nitric Oxide Synthase Inhibitor L-NMMA on the Human Ventilatory Response to Hypoxia

Although it is well known that nitric oxide (NO) production is involved in several physiological functions (e.g., vasodilatation, platelet inhibition, immune responses, cell adhesion and neurotransmission), its role in the regulation of respiration is less clear. In carotid body studies, most studies indicate that NO appears to play an inhibitory role in response to hypoxia (Gozal, Gozal, Gozal and Torres 1996a; Gozal, Torres, Gozal and Littwin 1996b; Iturriaga, Villanueva and Mosqueira 2000; Trzebski, Sato, Suzuki and Sato 1995; Valdes, Mosqueira, Rey, Del Rio and Iturriaga 2003). However, there is less agreement for studies carried out in the nucleus tractus solitarius (NTS), with some studies indicating that NO may play an excitatory role in response to hypoxia (Kline, Yang, Huang and Prabhakar 1998; Vitagliano, Berrino, D'Amico, Maione, De Novallis and Rossi 1996) and others suggesting that NO plays an inhibitory role (Haxhiu, Chang, Dreshaj, Erokwu, Prabhakar and Cherniack 1995; Ogawa, Mizusawa, Kikuchi, Hida, Miki and Shirato 1995). Further, the aforementioned studies have been carried out in experimental animal models and it is unclear whether NO is involved in the regulation of respiration in humans. Thus, we sought to elucidate the effects of systemic administration of N^g-Monomethyl-L-arginine (L-NMMA) on the response of ventilation (Ve) to 20 min of isocapnic hypoxia in human volunteers.