How does lactic acid affect blood vessel size?
1. Activation of TRPV1 receptors: Lactic acid can directly activate transient receptor potential vanilloid 1 (TRPV1) receptors, which are ion channels expressed in the smooth muscle cells of blood vessels. When activated, TRPV1 receptors allow the influx of calcium and sodium ions into the cells, leading to smooth muscle relaxation and vasodilation.
2. Inhibition of voltage-gated potassium channels: Lactic acid can inhibit voltage-gated potassium (Kv) channels in vascular smooth muscle cells. Kv channels are responsible for maintaining the resting membrane potential of cells. By blocking these channels, lactic acid prevents the efflux of potassium ions and causes membrane depolarization. This depolarization leads to increased calcium influx through voltage-gated calcium channels, resulting in smooth muscle contraction and vasoconstriction. However, at higher concentrations, lactic acid can reverse this effect and induce vasodilation. This biphasic response is thought to involve additional mechanisms beyond Kv channel inhibition.
3. Activation of endothelial nitric oxide synthase (eNOS): Lactic acid can stimulate the release of nitric oxide (NO) from the endothelium, the inner lining of blood vessels. NO is a potent vasodilator that relaxes vascular smooth muscle cells by increasing the production of cyclic guanosine monophosphate (cGMP). Increased cGMP levels lead to decreased intracellular calcium concentrations, smooth muscle relaxation, and vasodilation.
4. Modulation of sympathetic nerve activity: Lactic acid can also affect blood vessel size indirectly by modulating sympathetic nerve activity. Sympathetic nerve stimulation generally causes vasoconstriction. Lactic acid can inhibit sympathetic nerve activity, reducing vasoconstrictor tone and promoting vasodilation.
It's worth noting that the effects of lactic acid on blood vessel size can vary depending on the concentration, local tissue environment, and overall physiological conditions. In some cases, lactic acid may have both vasodilatory and vasoconstrictor effects, and the net outcome can depend on the balance of these opposing influences.