Contrasting effects of hypoxia on tension in rat pulmonary and mesenteric arteries

Abstract

The effects of hypoxia on resting and K-stimulated tension were tested on small rings of rat pulmonary and mesenteric resistance arteries (SPA and SMA, respectively) and on the large branches of the main pulmonary artery (LPA). Reduction of PO2 from approximately 135 Torr to less than 40 Torr slowly increased SPA and LPA resting tension but did not affect SMA tension. The increases in SPA and LPA tension during hypoxia were reversible and were dependent on external Ca2+. Verapamil, 10(-6) M, inhibited the hypoxic pulmonary vasoconstriction by 53-78%. The hypoxia-contracted SPA and LPA were relaxed by 2-4 microM cromakalim; these relaxations were reversed by 2 microM glibenclamide. Hypoxia attenuated the K-stimulated tension (delta TK) in both SPA and SMA at all external K+ concentrations ([K+]o = 10-100 mM) without affecting the shapes of the respective [K+]o-tension curves. However, the SPA curve was located much farther to the left on the [K+]o axis than the SMA curve. [K+]o congruent to 13 mM evoked a half-maximal increase in SPA tension; maximal delta TK was observed at [K+]o greater than or equal to 30 mM. In contrast, [K+]o less than 20 mM induced a negligible increase in SMA tension, whereas 35-40 mM K+ activated about one-half of the increase in tension elicited by 100 mM K+. The LPA [K+]o-tension curve in normoxia was intermediate between the SMA and SPA curves, but hypoxia shifted the LPA curve to the left: delta TK was augmented at [K+]o less than 20 mM and attenuated at high [K+]o.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of agonist-induced vasoconstriction in mouse pulmonary artery

“…For example, membrane depolarization by high K ϩ caused a slow and sustained contraction in mouse PA rings; the kinetics are very similar to that observed in rat PA (1,54,66,68) and human (55) PA rings. Removal of extracellular Ca 2ϩ and application of Nif almost abolished the high K ϩ -mediated PA contraction, as in rat (66). However, while PE induced contraction similarly in mouse and rat PA (44,52), removal of extracellular Ca 2ϩ almost abolished the PE-induced contraction, but Nif treatment only reduced the active tension by 60%, indicating that Ca 2ϩ resources other than influx via voltage-dependent Ca 2ϩ channels are involved in agonistmediated PA contraction.…”

“…Our findings suggest that the mouse PA bears similar electropharmacological mechanical properties to PA rings from rats (7,13,22,42,44,46,54,60,61,68) and humans (24,55). For example, membrane depolarization by high K ϩ caused a slow and sustained contraction in mouse PA rings; the kinetics are very similar to that observed in rat PA (1,54,66,68) and human (55) PA rings. Removal of extracellular Ca 2ϩ and application of Nif almost abolished the high K ϩ -mediated PA contraction, as in rat (66).…”

Hypoxia inhibits gene expression of voltage-gated K+ channel alpha subunits in pulmonary artery smooth muscle cells.

“…The resultant decrease in K V currents ( I K(V) ) depolarizes the myocytes, increases [Ca ] cyt , and causes pulmonary vasoconstriction (11)(12)(13)(14). Chronic exposure to hypoxia (1-20 d) causes a steady increase in pulmonary arterial pressure that is significant by day 2 and maximized by day 20 (15).…”

Patho-, physiological roles of voltage-dependent K+ channels in pulmonary arterial smooth muscle cells

“…This effects of accompanied by an enhancement of the inward Ca 2+ current in the pulmonary artery, an effect not observed in MASMCs (Yuan et al, 1990;Yuan et al, 1993). Delayed rectifier currents that are sensitive to 4-AP are deemed to be important determinants of resting membrane potential (Em) and critical in the initiation of HPV (Post et al, 1992;Archer et al, 1998).…”