Ascent to altitude presents a significant challenge to the human body. Specifically, it is associated with an increased ventilation and pulmonary vasoconstriction. In healthy subjects these are related such that a high ventilatory drive is associated with blunted pulmonary vasoconstriction. Adults born prematurely and given supplemental oxygen at birth have a blunted ventilatory response to hypoxia. We hypothesized that the hypoxic ventilatory and pulmonary vasoconstrictor responses would be unrelated following perinatal supplemental oxygen exposure. To test our hypothesis, we used a well-established rat model of 80% O2 (80%) exposure for 14 days post-natally, with 21% O2 exposure as a control (21%). We assessed the ventilatory response to graded hypoxia using barometric plethysmography 6-9 months post hyperoxia exposure. The left and right ventricles were catheterized to evaluate the hemodynamic response to 10 minutes of 12% O2 (hypoxia). To our surprise we found that 80% animals did not demonstrate a depressed ventilatory response to hypoxia. However, these animals experienced increased right ventricular systolic pressure in response to 12% O2. An increase in cardiac output was the primary driving force behind the increase in right ventricular end systolic pressure, not an increase in vascular resistance. We found no relationship between the hypoxic ventilatory drive and right ventricular pressure. In 21% animals exposed to hypoxia, the increase in right ventricular pressure was driven primarily by vasoconstriction and, as previous studies have shown, there was a relationship between the ventilatory and pressure responses. These data suggest that neonatal supplemental oxygen alters the hemodynamic response to hypoxia, possibly through enhanced sympathetic drive. The relationship between ventilation and pulmonary pressure may not translate to individuals born prematurely.

La prise en charge d’une hypertension artérielle est un enjeu majeur dans certaines situations à risque telles que la pré-éclampsie ou chez les patients avec une pathologie respiratoire pour lesquels la vasoconstriction hypoxique pulmonaire est bénéfique. L’urapidil est un antihypertenseur d’action mixte associant une action antagoniste sur les récepteurs alpha-1 adrénergiques post synaptiques périphériques et une baisse du tonus sympathique par action centrale qui pourrait impliquer à la fois un blocage des récepteurs alpha-1 et une activité agoniste sérotoninergique sur les récepteurs 5HT1A qui limite la survenue d’une tachycardie reflexe. La première étude indique que les récepteurs 5HT1A périphériques ne semblent pas impliqués dans les effets vasculaires périphériques de l’urapidil, qui seraient principalement le résultat du blocage des récepteurs alpha 1 adrénergiques. La deuxième étude montre que l’urapidil préserve la VHP contrairement à la nicardipine et la clévidipine qui l’inhibent. / Urapidil, a vasodilator, is widely used in the treatment of hypertension mostly due to better patient tolerance. Urapidil has a dual action: firstly it works as a selective alpha1- adrenoreceptor antagonist and secondly as an agonist of 5-HT1A receptors in the central nervous system. Thus, the present findings, while confirming that urapidil is a potent inhibitor of alpha 1-adrenoceptor-induced contraction targeting preferentially arteries with an endothelial dysfunction, do not support the role of 5-HT1A receptor activation in the control of the vascular tone in response to urapidil in the three types of blood vessels studied. In conclusion, this trial showed that in our experimental setting, urapidil preserved the hypoxia triggered vasoconstriction in isolated pulmonary vessels. Conversely, both calcium channel inhibitors nicardipine and clevidipine blunted the vasocontrictor reaction to hypoxia. These findings may have important clinical consequences that deserve further evaluation.