Changes in cytosolic Ca2+ measured by use of fura-2 and contraction produced by quick stretch and various stimulants in canine cerebral artery

Mechanical stimulation such as stretch generates myogenic contraction in ce rebral arteries. Myogenic contraction of cerebral arteries in response to q uick stretch is greatly modified by promoters and inhibitors of Ca2+ handli ng mechanisms including Ca2+ channel blockers. In the present study, in ord er to improve our understanding of the role of Ca2+ in the generation of st retch-induced contraction, changes in cytosolic free Ca2+ concentrations ([ Ca2+](cyt)) and contraction of canine cerebral artery in response to quick stretch were simultaneously measured by use of fura-2. The [Ca2+](cyt)-tens ion relationship in the stretch-induced contraction was compared with those by various stimulants. Quick stretch at a rate of 10 cm/sec with the amoun t of 40% of the initial muscle length (=100%) produced a myogenic contracti on in canine cerebral artery. The arterial [Ca2+](cyt) enormously increased after the stretch, which preceded the occurrence of the delayed contractio n in response to stretch. [Ca2+](cyt)-tension relationships in the stretch- induced contraction changed counterclockwise as those in the contractions i nduced by high KCl and pharmacological agonistic stimulants such as 5-hydro xytryptamine (5-HT) and endothelin-1 (ET-1). The contraction in response to quick stretch at the maintenance phase was far smaller than those produced by high KCl or agonistic stimulants at the same changes in [Ca2+](cyt). Th ese findings suggest that in the cerebral artery contraction in response to quick stretch, elevated cytosolic Ca2+ is utilized less efficiently as com pared with the contractions elicited by other stimulants. The apparent low Ca2+ sensitivity of stretch-induced contraction in dog cerebral artery migh t be related to the low efficiency of cytosolic Ca2+ elevated by the Ca2+ r elease from intracellular storage sites upon stretch.