J Appl Physiol 102: 2075a-2076a, 2007;
doi:10.1152/japplphysiol.01258c.2006
8750-7587/07 $8.00
POINT-COUNTERPOINT
REBUTTAL FROM DRS. ROCHEFORT AND MICHELAKIS
Opening his argument, our opponent calls you, the readers, to a gambling exercise; admittedly a safe bet. Because in one of his reviews on the subject, only four papers found the endothelium to be nonessential for HPV, compared to the 15 that found it to be essential (1), he asks you to bet your money on his side of the argument. However, even in Las Vegas you get in trouble if you play safe bets, but with weighted dice! To support their side of the story in that review, the authors listed (in Table 1 of that review) apparently all the papers that were studying sustained HPV (more than 20 min of hypoxia) (1). We do not understand the basis on which 20 min was used as the cutoff between acute and "sustained HPV." But, even using this rule, several papers were omitted from that table and argument, which, interestingly, strongly suggest a nonessential role of the endothelium. For example, Wang et al. (3) studied isolated lamb pulmonary arteries: even up to 120 min of hypoxia, caused the same constriction in the vessels with and without endothelium. In fact, the endothelium-denuded vessels had a faster constriction to hypoxia. Jane Madden's work [including the paper that we discussed in our argument and in our Fig. 1A (2)] is also not included in the 4/15 argument. We could improve the odds more by adding papers from our group (published before and after that review), but lucky you, you are scientists and not gamblers.
Nevertheless, this Point:Counterpoint series proves to be much easier to settle than expected. For example, our opponent alerts you to the fact that we would try to downgrade the importance of endothelial-derived factors by presenting them as modulators of HPV. But we do not really have to. He has done this for us, in the "gambler's guide to HPV," that he offered you (2). The conclusion of this review reads: "mediators derived from the pulmonary vascular endothelium exert a powerful modulating influence on the response of the pulmonary circulation to hypoxia." We could not agree more.
In his current argument, our opponent concludes: "It is, therefore, possible that the activation of Rho kinase during sustained HPV represents the bridge between physiological HPV... and the pathophysiological consequences of chronic hypoxia."
REFERENCES
- Aaronson PI, Robertson TP, Ward JP. Endothelium-derived mediators and hypoxic pulmonary vasoconstriction. Respir Physiol Neurobiol 132: 107–120, 2002.[CrossRef][ISI][Medline]
- Madden JA, Vadula MS, Kurup VP. Effects of hypoxia and other vasoactive agents on pulmonary and cerebral artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 263: L384–L393, 1992.[Abstract/Free Full Text]
- Wang Y, Coe Y, Toyoda O, Coceani F. Involvement of endothelin-1 in hypoxic pulmonary vasoconstriction in the lamb. J Physiol 482: 421–434, 1995.[Abstract/Free Full Text]
Copyright © 2007 by the American Physiological Society.
