Nitric oxide synthase inhibition does not affect the exercise-induced arterial hypoxemia in Thoroughbred horses

Abstract

Because sensitivity of equine pulmonary vasculature to endogenous as well as exogenous nitric oxide (NO) has been demonstrated, we examined whether endogenous NO production plays a role in exercise-induced arterial hypoxemia. We hypothesized that inhibition of NO synthase may alter the distribution of ventilation-perfusion mismatching, which may affect the exercise-induced arterial hypoxemia. Arterial blood-gas variables were examined in seven healthy, sound Thoroughbred horses at rest and during incremental exercise protocol leading to galloping at maximal heart rate without (control; placebo = saline) and with N(omega)-nitro-L-arginine methyl ester (L-NAME) administration (20 mg/kg iv). The experiments were carried out in random order, 7 days apart. At rest, L-NAME administration caused systemic hypertension, pulmonary hypertension, and bradycardia. During 120 s of galloping at maximal heart rate, significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, hyperthermia, and acidosis occurred in the control as well as in NO synthase inhibition experiments. However, statistically significant differences between the treatments were not found. In both treatments, exercise caused a significant rise in hemoglobin concentration, but the increment was significantly attenuated in the NO synthase inhibition experiments, and, therefore, arterial O(2) content (Ca(O(2))) increased to significantly lower values. These data suggest that, whereas L-NAME administration does not affect pulmonary gas exchange in exercising horses, it may affect splenic contraction, which via an attenuation of the rise in hemoglobin concentration and Ca(O(2)) may limit performance at higher workloads.

Intrapulmonary arteriovenous shunts of >15 μm in diameter probably do not contribute to arterial hypoxemia in maximally exercising Thoroughbred horses

“…Our findings regarding development of significant hyperthermia, arterial hypoxemia, desaturation of hemoglobin, hypercapnia, and acidosis during galloping at 14 m/s on a 3.5% uphill grade in the present study (Table 1) are consistent with previously reported data in maximally exercising Thoroughbred horses (13)(14)(15)(16). It has also been reported that submaximal exercise performed at 8 m/s on a 3.5% uphill grade did not result in arterial hypoxemia (13)(14)(15)(16); this was also true in the present study (Table 1).…”

“…Vigorously agitated, ultrasonicated suspension of 15-m-diameter stable isotope-labeled microspheres was injected into the right atrium at 30 s of galloping at 14 m/s on a 3.5% uphill grade, when exercise-induced arterial hypoxemia is known to be well developed in Thoroughbred horses (13)(14)(15)(16). Blood withdrawal from the aorta and the pulmonary artery continued until 90 s postinjection of microspheres.…”

“…10 -12)] and 2) the exercise-induced arterial hypoxemia tends to be more pronounced in racehorses [arterial O 2 tension and hemoglobin O 2 saturation in maximally exercising racehorses usually decreasing (from near 100 mmHg and ϳ98 -99%, respectively, at rest) to ϳ75 mmHg and ϳ85%, respectively; Refs. [13][14][15][16], it was hypothesized that dormant intrapulmonary arteriovenous shunts similar to those described in exercising human subjects (5, 22a) may become functional in strenuously exercising racehorses, thereby contributing to the observed arterial hypoxemia and desaturation of hemoglobin. Thus our primary objective in the present study was to determine whether intrapulmonary arteriovenous shunts become functional in the lungs of Thoroughbred horses performing short-term, high-intensity exercise capable of eliciting maximal heart rate, stress failure of pulmonary capillaries leading to exercise-induced pulmonary hemorrhage (EIPH), and significant arterial hypoxemia and desaturation of hemoglobin.…”

“…This is because, assuming that a constant fraction of total pulmonary blood flow bypasses the gas-exchange areas of the equine lungs via intrapulmonary arteriovenous shunts during 30 -120 s of maximal exertion, the observed significant reductions in mixed venous blood oxygenation should cause a significant reduction in arterial O2 tension, which was not the case in our horses. Thus it is suggested that intrapulmonary arteriovenous shunting probably does not contribute to the exercise-induced arterial hypoxemia in racehorses.blood gas tensions during exertion; arterial desaturation during exercise; pulmonary microcirculation; microspheres IT IS WELL KNOWN THAT STRENUOUSLY EXERCISING racehorses experience significant arterial hypoxemia and desaturation of hemoglobin, and it is reported that these changes in arterial oxygenation limit athletic performance (1,3,8,(13)(14)(15)(16)24). A significant arterial hypercapnia is also observed in strenuously exercising Thoroughbred horses despite significantly increased alveolar ventilation.…”

“…blood gas tensions during exertion; arterial desaturation during exercise; pulmonary microcirculation; microspheres IT IS WELL KNOWN THAT STRENUOUSLY EXERCISING racehorses experience significant arterial hypoxemia and desaturation of hemoglobin, and it is reported that these changes in arterial oxygenation limit athletic performance (1,3,8,(13)(14)(15)(16)24). A significant arterial hypercapnia is also observed in strenuously exercising Thoroughbred horses despite significantly increased alveolar ventilation.…”