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Response of nitric oxide pathway to l-arginine infusion at the altitude of 4,350 m

¹ Association pour la Recherche en Physiologie de l'Environnement, UFR Médecine, 93017, Bobigny, France, ² UFR Médecine Necker, 75014, Paris, France

CORRESPONDENCE: J-P. Richalet, ARPE UFR Médecine, 74, rue M. Cachin, 93017, Bobigny cedex, France. Fax: 33 148387777

Keywords: cyclic guanosine 3',5'-monophosphate, hypoxia, l-citrulline, nitric oxide

Received: August 18, 2000
Accepted March 26, 2001

It was hypothesized that hypoxia may inhibit nitric oxide (NO) production by reducing the availability of endothelial NO synthase (NOS III) substrate.

To evaluate the effect of l-arginine on the NO release in high altitude, 11 subjects were infused with l-arginine (0.5 g·kg^–1) during 30 min in normoxia and after 36 h at 4,350 m (hypoxia). The l-citrulline and cyclic guanosine monophosphate (cGMP) concentrations were measured to investigate NO synthesis and guanylyl cyclase activity respectively. l-citrulline concentration, arterial oxygen saturation (S_a,O2), systemic blood pressure, heart rate and acute mountain sickness (AMS) score were measured at rest and 15, 30 and 45 min after starting infusion.

The results showed that baseline l-citrulline was lower in hypoxia (p<0.05). l-arginine infusion increased l-citrulline concentration in both conditions. However, in hypoxia l-citrulline concentration remained lower than in normoxia (p<0.05). The concentration of cGMP was lower in hypoxia (p<0.05). In hypoxia, S_a,O2 increased from 15 min after the start of the infusion to 45 min (p<0.05). Blood pressure and heart rate were not affected by l-arginine infusion.

Subjects who experienced symptoms of AMS showed a slight decrease in AMS score with l-arginine.

The decreased l-citrulline suggests a hypoxia-induced impairment of nitric oxide synthase III or a decrease in l-arginine availability. The improvement of arterial oxygen saturation by pretreatment with l-arginine could be ascribed to an enhancement of the ventilation/perfusion ratio. Collectively, these results are consistent with a decrease in nitric oxide production in hypoxia that could be antagonized by supplying nitric oxide synthase cosubstrate.

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