"We propose to change the default P-value threshold forstatistical significance for claims of new discoveries from 0.05 to 0.005."

PA12 may act as a circulating substrate for cardiac chymase-mediated AngII production, in contrast to ACE-mediated AngII production from AngI.

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Hypoxic vasoconstriction (HV) is an intrinsic response of mammalian pulmonary vascular smooth muscle (VSM). In the present study, HV was examined by myography of vessel rings from three primitive vertebrates: New Zealand hagfish (NZH), Pacific hagfish (PH), and sea lamprey (SL). Hypoxia dilated pre-gill arteries (ventral aorta, afferent branchial) from all species, whereas it contracted systemic arteries [dorsal aorta (DA), efferent branchial, celiacomesenteric]. DA HV was reproducible over several days, and it could be sustained in NZH for 8 h without adverse effects. Tension was proportional to PO(2), and half-maximal HV was obtained at PO(2) (mmHg) of 4.7 +/- 0. 2 (NZH), 0.8 +/- 0.1 (PH), and 10.7 +/- 1.9 (SL). HV did not require preconditioning (preexisting contractile stimulus) and was unaffected by elevated extracellular potassium (200 mM NZH; 80 mM SL); removal of the endothelium (NZH); or inhibitors of cyclooxygenase, lipoxygenase, cytochrome P-450 or antagonists of alpha-adrenergic, muscarinic, nicotinic, purinergic, or serotoninergic receptors. These results show that HV is an intrinsic feature of systemic VSM in cyclostomes and suggest that HV has been in the repertoire of VSM responses, since the origin of vertebrates. The exceptionally hardy HV in cyclostome DA may provide a useful model with which to examine both the phylogeny and mechanisms of this response.