An alternative, non-mammalian model for the study of hypoxic vasoconstriction (Petromyzon marinus)

Hypoxic pulmonary vasoconstriction (HPV) matches ventilation to perfusion in the normal mammalian lung. High altitude, sleep apnea, and pulmonary disease produce a global HPV that leads to pulmonary hypertension, right ventricular hypertrophy, and heart failure. The mechanisms underlying HPV remain unresolved due in large part to the lack of a consistent mammalian model. Smooth muscle myography, calcium (Ca2+) fluorophores, radioimmunoassay, and scanning electron microscopy were utilized in the present study to examine a primitive, non-mammalian model of hypoxic vasoconstriction (HV).; The monophasic HV in dorsal aortas (DA) from sea lamprey, Petromyzon marinus, was independent of endothelial or neural factors. HV was directly correlated with oxygen tension (Po₂), producing a half-maximal contraction (P₅₀) at a Po₂ of 10.7 ± 1.9 mmHg.; HV in lamprey DA was temporally correlated with increased free cytosolic calcium (Ca2+_c) released almost exclusively from intracellular Ca2+ stores. A sodium (Na+ _o)/Ca2+ exchange mechanism was evident in lamprey DA, but it was either inhibited or not utilized during HV, because DA relaxed to pre-hypoxic tension following return to normoxia in zero Na+ _o. Levels of cGMP in DA smooth muscle were increased by atrial natriuretic peptide (ANP), decreased by methylene blue (MB), and unchanged by hypoxia.; Chloride (Cl−) channels may be important modulators of tone in lamprey DA, because substitution of extracellular Cl− increased tone and during hypoxia produced an augmented HV, which persisted through several exposures. HV was not dependent on potassium channels but vessels were sensitive to osmotic shrinkage. Stepwise changes in tension were noted with addition of KCl (up to 200 mM), NaCl (up to 200 mM), or sucrose (up to 400 mM) to vessel baths.; Rat pulmonary arteries were conditioned through controlled environment and repeated stimulation to produce a monophasic hypoxic contraction resembling the lamprey HV. Examination of the dose-dependence of HV in rat pulmonary artery produced a P₅₀ of 15.0 ± 2.4 mmHg.; These results show that HV is an ancient response and that lamprey DA may be the best model for uncovering the intrinsic mechanisms underlying HV. The conditioning effect on rat PA allows for direct comparison of lamprey and mammalian responses.