MYOGENIC CONTRACTION BY MODULATION OF VOLTAGE-DEPENDENT CALCIUM CURRENTS IN ISOLATED RAT CEREBRAL-ARTERIES

1. Tissue blood flow and blood pressure are regulated by the spontaneo us, myogenic, contraction developed by resistance arteries. However, t he cellular mechanisms underlying myogenic contraction are not underst ood. In this study the mechanisms of myogenic contraction in cerebral resistance arteries were investigated. 2. The vasoconstriction observe d in response to increased pressure in cerebral resistance arteries (m yogenic reactivity) was dependent on Ca2+ entry through voltage-depend ent Ca2+ channels, since it was abolished by Ca2+ removal and by dihyd ropyridine antagonists of voltage-dependent Ca2+ channels. 3. Myogenic reactivity persisted in a high-K+ saline, with reduced Ca2+, where me mbrane potential is presumed to be clamped. Therefore, membrane depola rization alone does not fully account for the increased voltage-depend ent Ca2+ channel opening. 4. Voltage-dependent Ca2+ currents in single smooth muscle cells isolated from the resistance artery were substant ially increased by applying positive pressure to the patch electrode e voking membrane stretch. 5. Myogenic reactivity remained unaffected by ryanodine and therefore was independent of internal ryanodine-sensiti ve Ca2+ stores. 6. The myofilament Ca2+ sensitivity was not increased by elevated pressure in alpha-toxin-permeabilized arteries. However, p harmacological activation of protein kinase C or G proteins did increa se the myofilament Ca2+ sensitivity. 7. Myogenic contraction over the pressure range 30-70 mmHg could be accounted for by an increase in [Ca 2+](i) from 100 to 200 nM. 8. It is concluded that modest increases in [Ca2+](i) within the range 100-200 nM can account for that myogenic c ontraction, and that stretch-evoked modulation of Ca2+ currents may co ntribute to the myogenic response.