Myogenic contraction by modulation of voltage‐dependent calcium currents in isolated rat cerebral arteries.

Abstract

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.

Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure

“…Elevating bath [calcium] to 400 nÒ maximally constricted these permeabilized, pressurized arteries (McCarron et al 1997), very similar to our intact artery data. Therefore, our data and the data of McCarron et al (1997) strongly support the idea that the major calcium entry pathway in these cerebral arteries is the dihydropyridine-sensitive, voltage-dependent calcium channel and that the dynamic range of steady arterial wall calcium is 100-400 nÒ.…”

“…For example, membrane depolarization of a pressurized (60 mmHg) cerebral artery from −45 mV by •9 mV would elevate global [calcium] by •45 nÒ and constrict the vessel by about 25% . In accord with our study, raising bath [calcium] from 100 to 200 nÒ constricted permeabilized, pressurized (70 mmHg) cerebral arteries to a diameter observed in the intact pressurized artery (McCarron et al 1997). Elevating bath [calcium] to 400 nÒ maximally constricted these permeabilized, pressurized arteries (McCarron et al 1997), very similar to our intact artery data.…”

“…11). At membrane potentials positive to about 0 mV, pressure may also activate dihydropyridine-sensitive, voltage-dependent calcium channels, independent of membrane potential changes (McCarron, Crichton, Langton, MacKenzie & Smith, 1997). Elevation in intravascular pressure has been shown to elevate steady-state calcium in arterioles of the hamster cheek pouch, and this led to an elevation in myogenic constriction (D'Angelo et al 1997).…”

Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog

“…After a resting period of 10 min, five pressure reductions were conducted (n ϭ 6) under control conditions at 10,20,30,35, and 40 min after the start of the experiment, i.e., with intercalated recovery periods of 9 min between the first three and 4 min between the last three pressure reductions. Nine minutes after the last pressure reduction, furosemide was injected (20 mg/kg iv; i.e., Ͼ600 mg).…”

“…The response time of the myogenic response in renal vessels (3-10 s) is considerably faster than that in other vascular beds (30-120 s), such as those in skeletal muscle (16,18,25), brain (35,39), and skin (15,34). Although these temporal differences have been experimentally investigated by studying the renal and the mesenteric circulation (1) and discussed in a recent review (20), a direct comparison with other vascular beds to our knowledge has never been done, except for a cursory notion in the original work of Bayliss (5) and a step function analysis in artificially perfused organs (31).…”