Case Study in Discrepancies

As a final note to this chapter, it is fitting to show how studying the same process in different models can lead to different results and different conclusions. In piglet pulmonary artery and vein rings inhibiting NO synthase completely blocked alkalosis-induced relaxation. However, in isolated piglet lungs, NO synthase inhibition had no effect on the vasodilation. In an effort to determine which factors contributed to this discordance the contribution of pressor stimuli, (hypoxia versus the thromboxane mimetic U46619), perfusate composition, (blood versus physiological saline solution), and flow were assessed (15). Effects of NO synthase inhibition on the alkalosis-induced vasodilation were compared in intact piglets, and in 150-350 Jim cannulated arteries and by angiography of 150-900 Jim in situ arteries. Neither pressor stimulus, perfusate composition nor flow affected the results, i.e., NO synthase inhibition fully abolished alkalosis-induced vasodilation in the cannulated arteries but failed to do so in the isolated lungs. These data indicated that other factors such as perivascular tissue (adventitia and parenchyma) and remote signalling pathways may contribute to the discordant responses. Regardless ofthe mechanism involved in the response to alkalosis, this study illustrates the limitations of applying conclusions derived from a reductionist model to the whole animal.

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