1. Tissue blood flow and blood pressure are regulated by the spontaneous, myogenic, contraction developed by resistance arteries. However, the cellular mechanisms underlying myogenic contraction are not understood. In this study, the mechanisms of myogenic contraction in cerebral resistance arteries were investigated. 2. The vasoconstriction observed in response to increased pressure in cerebral resistance arteries (myogenic reactivity) was dependent on Ca2+ entry through voltage‐dependent Ca2+ channels, since it was abolished by Ca2+ removal and by dihydropyridine antagonists of voltage‐dependent Ca2+ channels. 3. Myogenic reactivity persisted in a high‐K+ saline, with reduced Ca2+, where membrane potential is presumed to be clamped. Therefore, membrane depolarization alone does not fully account for the increased voltage‐dependent Ca2+ channel opening. 4. Voltage‐dependent Ca2+ currents in single smooth muscle cells isolated from the resistance artery were substantially increased by applying positive pressure to the patch electrode evoking membrane stretch. 5. Myogenic reactivity remained unaffected by ryanodine and therefore was independent of internal ryanodine‐sensitive Ca2+ stores. 6. The myofilament Ca2+ sensitivity was not increased by elevated pressure in alpha‐toxin‐permeabilized arteries. However, pharmacological activation of protein kinase C or G proteins did increase the myofilament Ca2+ sensitivity. 7. Myogenic contraction over the pressure range 30‐70 mmHg could be accounted for by an increase in [Ca2+]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 contraction, and that stretch‐evoked modulation of Ca2+ currents may contribute to the myogenic response.

with a small depression in the apparent Ca2+ sensitivity of tension production. This effect of pH on maximum (100 /M Ca2+) and submaximum (0-3 /im Ca2+) Ca2+-activated force was observed over a range of acidic pHs (7 0-6-7).5. Increasing pH from 7-2 to 7-7 at a [Pi] of 1 mm depressed Ca2+-activated force with no effect on Ca2+ sensitivity of tension production.6. Spontaneous contractions in intact rat myometrium are abolished under hypoxic conditions. Under these same conditions intracellular [Pi] rises and pH falls.The results of this study suggest that taken individually neither the effect of a rise in [Pi] nor a fall in pH on Ca2+-activated force generated by the contractile proteins can account for the effect of hypoxia on spontaneous contractions.

There appear to be distinct differences in the response of large arteries and resistance arteries to altered intracellular pH which may be based on the different properties of the smooth muscle within the wall of each blood vessel. Similarly, systemic and pulmonary vessels may respond differently, but no systematic study exists to allow a more definitive conclusion. Factors controlling intracellular pH such as intracellular buffering power and sarcolemmal pH regulating mechanisms may differ across the vascular bed and may contribute to some of the differences observed in response to altered extracellular pH. Finally, few studies have examined the pH sensitivity the intracellular processes involved in basal tone and pharmaco-mechanical coupling in vascular smooth muscle. More information concerning these latter aspects of smooth muscle function is required to progress the understanding of the modulator action on pH on vascular tone.

Recent work has indicated that there is a major difference in the Ca2+ store of smooth muscle from rat and guinea-pig ureter; with the rat store being agonist-sensitive but ryanodine insensitive and the guinea-pig store being ryanodine sensitive but agonist insensitive [Th. V. Burdyga, M.J. Taggart, S. Wray, J. Physiol. 489 (1995) 327-335]. We have therefore examined directly the mechanism of Ca2+ release from the internal Ca2+ store (SR). Following permeabilisation with alpha-toxin or beta-escin the SR was Ca(2+)-loaded before application of carbachol or caffeine. Only carbachol evoked a transient contraction in rat ureter. The carbachol-induced contraction was blocked by heparin and cyclopiazonic acid (CPA) but not ryanodine. Only caffeine produced contraction in guinea-pig ureter, and this was blocked by ryanodine. Direct application of IP3 caused a small transient contraction in rat but not guinea-pig ureter. We conclude that rat ureter possesses only an IP3 sensitive store while guinea-pig ureter only has a ryanodine sensitive store.