Biphasic contractile response of pulmonary artery to hypoxia

Abstract

Isolated perfused lungs exposed to low O2 exhibit a hypoxic pulmonary vasoconstriction response that is transient in nature. The purpose of this study was to determine whether the isolated pulmonary artery behaves similarly in response to hypoxia. Rat pulmonary arterial rings were placed in tissue baths (37 degrees C, air-5% CO2, pH = 7.4) and attached to force transducers. Maximum contractile responses (Po) to high K+ were elicited. After washout, arterial rings were submaximally contracted and made hypoxic (PO2 = 33.7 +/- 1.3, pH = 7.38 +/- 0.01). Aortic rings were used to obtain comparative data. The isolated pulmonary arterial hypoxic response was biphasic, displaying an initial rapid contraction of short duration (phase 1) then, before complete relaxation of this first response, a second slow but sustained contraction occurred (phase 2). Aortic rings did not exhibit a biphasic response, but showed only an initial short contraction followed by complete relaxation. The contractile response of the pulmonary artery was diminished when the endothelium was rendered nonfunctional. However, the phase 2 response was not endothelium dependent. Neither inhibitors of the lipoxygenase or cyclooxygenase pathways nor scavengers of extracellular reactive oxygen species had any effect on the biphasic hypoxic response. Pulmonary arterial hypoxic contractions were blunted when glucose was absent and appear to be dependent on glycolytic ATP. Results of this study show that hypoxia causes a biphasic contractile response of pulmonary arterial muscle and that two different mechanisms appear to be involved, since the transient phase 1 response is endothelium dependent, whereas the sustained contraction of phase 2 is endothelium independent.

Hypoxic pulmonary vasoconstriction and pulmonary artery tissue cytokine expression are mediated by protein kinase C

“…We and others (3,10,28) have reported that in isolated rat PA, a biphasic pattern of contraction occurs in response to acute hypoxia. The role of PKC on HPV in isolated perfused lung has been demonstrated in previous studies (1,32); however, the involvement of PKC in the isolated PA is less clear.…”

Hypoxia activates a potassium current in isolated smooth muscle cells from large pulmonary arteries of the rabbit

“…However, the response of the pulmonary artery to alveolar hypoxia is complex with vasorelaxation and vasoconstriction appearing at different stages and in different parts of the arterial arborization (Madden et al 1985;Bonnet, Argibay & Garnier, 1989;Bennie, Packer, Powell, Jin & Rhoades, 1991). In this report we show that severe hypoxia relaxes large diameter pulmonary arteries (PAs) of the rabbit and enhances rather than inhibits a K+ current in smooth muscle cells isolated from this tissue.…”

ETA receptors are the primary mediators of myofilament calcium sensitization induced by ET‐1 in rat pulmonary artery smooth muscle: a tyrosine kinase independent pathway

“…Hence, pulmonary arteries constrict biphasically when exposed to hypoxia (450 Torr). An initial transient constriction (phase 1) is followed by a slowly developing and sustained increase in tone (Albarwani et al, 1994;Bennie et al, 1991;Jin et al, 1992;Kovitz et al, 1993;Robertson et al, 1995), (phase 2). Phase 1 occurs independently of the endothelium and is thought to result from depolarization of the smooth muscle cell membrane (Evans et al, 1996;Osipenko et al, 1997;Yuan et al, 1993;Post et al, 1992) and Ca 2+ in¯ux through voltagegated Ca 2+ channels (Harder et al, 1985;McMurty et al, 1976;Madden et al, 1992;Corn®eld et al, 1993;Salvatera & Goldman, 1993;Vadula et al, 1993).…”