Basis of pH-independent inhibitory effects of lactate on 45Ca movements and responses to KCl and PGF2 alpha in canine coronary arteries.

Pulmonary O2 uptake and leg blood flow kinetics during moderate exercise are slowed by hyperventilation-induced hypocapnic alkalosis

“…Another possible contributor to the increase in FA diameter is lactate Ϫ , which is capable of causing vasodilation independently of acid-base changes (1,34,51,52). Lactate Ϫ accumulation in arterial plasma was greater in Hypo (ϳ5 mM) than in Con (ϳ3 mM) during Mod cycling exercise (13,45), a consequence of a slower activation of pyruvate dehydrogenase (PDH; requiring a greater substrate level phosphorylation) with Hypo (45) and enhanced transport out of the muscle via the sarcolemma monocarboxylate transporter (37).…”

Lactate depresses sarcolemmal permeability of Ca2+ in intact arterial smooth muscle

“…Neutralized lactate effects vascular tone even in the presence of neutral extracellular pH (Hester et al, 1980;Mori et al, 1998). However, lactate and pyruvate present in the extracellular space are taken-up into muscle cells by transport across the sarcolemma via the monocarboxylate-B-H + transporter (Barron et al, 2000); protons are transported together with the monocarboxylate species.…”

“…Vasodilation and depressed responsiveness of vascular smooth muscle to contractile agonists is known to occur under conditions in which the concentration of lactate in the surrounding medium is increased (Hester et al, 1980;Chen et al, 1996;Mohazzab-H et al, 1997;Barron et al, 1997;Mori et al, 1998). Under various physiological and pathophysiological conditions in which ambient lactate is increased (e.g., vigorous exercise, hypoxia, and sepsis), there may be concomitant acidosis, which alone can produce vasodepression.…”

“…Under various physiological and pathophysiological conditions in which ambient lactate is increased (e.g., vigorous exercise, hypoxia, and sepsis), there may be concomitant acidosis, which alone can produce vasodepression. Nevertheless, the lactate ion species itself has been shown to produce vasodepression experimentally independent of extracellular pH (Hester et al, 1980). Alterations in membrane potential (Mori et al, 1998), intracellular Ca 2 + (Barron et al, 1997;Mori et al, 1998;Favero et al, 1997), redox potential (Barron et al, 1997;Barron et al, 1998), and intracellular signaling involving NADH/NAD redox-induced superoxide production (Mohazzab-H et al, 1997;Chen et al, 1996;Gupte et al, 1999) have been implicated as mechanisms responsible for the effect of lactate on vascular tone, and the depressive effect of lactate on muscle contractility in general.…”

“…Alterations in membrane potential (Mori et al, 1998), intracellular Ca 2 + (Barron et al, 1997;Mori et al, 1998;Favero et al, 1997), redox potential (Barron et al, 1997;Barron et al, 1998), and intracellular signaling involving NADH/NAD redox-induced superoxide production (Mohazzab-H et al, 1997;Chen et al, 1996;Gupte et al, 1999) have been implicated as mechanisms responsible for the effect of lactate on vascular tone, and the depressive effect of lactate on muscle contractility in general. However, investigations concerning the effect of lactate on intracellular Ca 2 + and membrane potential in muscle and other cell types have been conflicting (Hester et al, 1980;Favero et al, 1997;Meats et al, 1989;Posterino and Fryer, 2000). Furthermore, an effect of lactate on free intracellular Ca 2 + in an intact arterial smooth muscle preparation has not been directly demonstrated.…”