Papaverine injection into the hindlimb circulation stimulates ventilation in sheep

To test the hypothesis, previously suggested by Huszczuk et al. (1993), that distention of the peripheral microvascular network could, per se, stimulate ventilation, the ventilatory effects of papaverine-induced muscular vasodilation were studied in ten anaesthetized sheep. Because systemic action of papaverine may involve the arterial baro- and chemoreceptors, the animals were surgically prepared for a reversible isolation of the hindlimb circulation. Papaverine injection (1-2 mg/kg) into the arterial inflow of the isolated limbs provoked a 13 +/- 6 sec-delayed increase in VE by 1.8 +/- 0.2 L min-1 (p < 0.01) with a concomitant decrease in peripheral vascular resistance and no decrease in the systemic arterial blood pressure. Identical control injection into a jugular vein prior to the hindlimb circulatory separation yielded an increase of VE by 4.95 +/- 0.58 L min-1 with a latency of 21 +/- 2 sec and a coinciding moderate decrease of the systemic arterial pressure. The present data suggest that papaverine injection into the hindlimb circulation can stimulate ventilation independently of its possible effects on the arterial baro- or chemoreceptors, supporting the hypothesis that muscular vasodilation could contribute to the control of breathing through a neural link.