Effects of combined increase in [H⁺] and [ADP] on resting tension and Ca²⁺ sensitivity in membrane permeabilized cerebral artery

Accumulation of H⁺ and ADP in cytoplasm plays an important role in modifying the cellular functions under pathological conditions such as hypoxia. Cerebral vasospasm is a major cause of death and disability after subarachnoid hemorrhage (SAH), of which pathogenesis, nevertheless, is poorly understood. Using β-escin-permeabilized basilar artery that enabled us to control the intracellular solute composition under near-physiological conditions, we studied the possible involvement of increased intracellular H⁺ ([H⁺]_i) and ADP ([ADP]_i) in the pathogenesis of cerebral vasospasm. It was found that combined increase in [H⁺] and [ADP] led to an increase in the resting tension and a subsequent irreversible increase in the Ca²⁺ sensitivity of contraction accompanying a high level of phosphorylation in smooth muscle 20-kDa myosin light-chain (MLC₂₀). The results suggest that intracellular metabolic inhibitions accompanying an increase in [H⁺]_i and [ADP]_i may play a role in the development of cerebral vasospasm after SAH through impairing the regulation of MLC₂₀ phosphorylation in arterial smooth muscle cells.