Voltage-Operated Calcium Channels Are Essential for the Myogenic Responsiveness of Cannulated Rat Mesenteric Small Arteries

Abstract

The role of L-type voltage-operated Ca²⁺ channels (VOCs) in myogenic responsiveness was studied in cannulated rat mesenteric small arteries [mean diameter at 100 mm Hg and full dilation was 329 ± 9 (SE) µm]. Twenty-six arteries were cannulated and pressurized. The luminal cross-sectional area of these vessels was monitored continuously. To test for myogenic responsiveness, pressure was raised stepwise from 20 to 60 and from 60 to 100 mm Hg. Pressure elevation enhanced the vascular tone, reflecting spontaneous myogenic responsiveness. Nifedipine (1 and 10 µM) suppressed spontaneous myogenic responses. The αi-adrenoceptor agonist phenylephrine (1 and 10 µM), when administered at 20 mm Hg, elicited constriction and vasomotion, and potentiated myogenic constriction to subsequent pressure elevation. Nifedipine (1 and 10 µM) also suppressed phenylephrine-potentiated myogenic responsiveness. Stimulation of VOCs with BAY K 8644 (10-300 mM) had no effect at 20 mm Hg, but augmented myogenic responsiveness. K⁺ (16-46 mM) caused concentration-dependent constrictions when administered at 20 mm Hg, and potentiated myogenic responsiveness when the pressure was raised from 20 to 60 mm Hg. Thus, any intervention that blocked the VOCs also blocked myogenic responses, and any form of stimulation of the VOCs also augmented myogenic responses. Therefore, we conclude that VOCs are essential for the myogenic responsiveness of cannulated rat mesenteric small arteries.

Intravascular pressure-evoked changes in intracellular calcium [Ca2+]i and tone in rat mesenteric and rabbit cerebral arteries in vitro

“…3,5 Myogenic contractile responses appear to be especially dependent on influx of extracellular Ca 2+ and can be abolished by the removal of extracellular calcium or the application of calcium channel blockers. 3,[5][6][7] Small arteries from different vascular beds display varying degrees of myogenic activity. Generally the response is most marked in those territories with the greatest degree of flow autoregulation, such as the cerebral and coronary circulations; 8,9 and least marked in those territories with little autoregulation, such as the mesenteric circulation.…”

“…Generally the response is most marked in those territories with the greatest degree of flow autoregulation, such as the cerebral and coronary circulations; 8,9 and least marked in those territories with little autoregulation, such as the mesenteric circulation. 7,10 The object of this study was to explore the relationship between myogenic contractile response and calcium mobilisation in small arteries from a cerebral and a mesenteric vascular bed in order to examine whether differences in pressure-evoked changes in [Ca 2+ ] i could account for differences in myogenic response in these arteries.…”

Extracellular Calcium and Vascular Responses After Forearm Ischemia

“…This causes Ca 2ϩ entry through voltage-gated Ca 2ϩ channels. [5][6][7] Despite some evidence suggesting that the myogenic response is due to changes in cellular Ca 2ϩ sensitivity, the majority of evidence supports the concept that calcium concentrations within smooth muscle cells must rise for myogenic constriction to occur. 8 This rise in intracellular calcium requires a net movement of the ion from the interstitium to the smooth muscle cells.…”

Aging and total stenosis triggers differential responses of carotid and basilar arteries to endothelin-1 and phenylephrine

“…Interestingly, the reduced reactivity to endothelin-1 is not due to a reduction of contractile machinery of the stenosed guinea pig carotid, since the contractile response of these arteries to phenylephrine, a selective α1-adrenoreceptor agonist, and KCl, a depolarizing agent, was also reduced by stenosis. Contractions of vascular tissues induced by KCl rely almost exclusively on Ca 2+ influx through activation of voltage-sensitive channels (Hudgins and Weiss, 1968), whereas contractions induced by phenylephrine are mediated by an increase in Ca 2+ influx through both receptor-operated channels (Hirata et al, 1998) and voltage-sensitive channels (Wesselman et al 1996;Lee et al, 2001). Likewise, endothelin-1-induced contraction involves the influx of extracellular Ca 2+ through receptor-operated and voltage-sensitive Ca 2+ channels (Rubany et al 1994).…”