Levcromakalim

Hamilton, T. C.; Beerahee, A; Moen, Jorunn; Price, R. K.; Ramji, J. V.; Clapham, John C.

doi:10.1111/j.1527-3466.1993.tb00276.x

Cited by 15 publications

(9 citation statements)

References 52 publications

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“…Noma discovered ATP-sensitive K + channels in cardiac myocytes (1097), and currents through similar channels were subsequently identified in many other cell types including vascular SMCs [see (9, 15, 68–72, 76, 166, 180, 219, 272, 273, 311, 322, 374, 375, 436, 506, 544, 661, 786, 826, 827, 984, 1070, 1111, 1182, 1183, 1187, 1188, 1332, 1464, 1595, 1604) for reviews]. These K + channels derive their name from their property that increases in intracellular ATP decrease their activity.…”

Section: Katp Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

259

347

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Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

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Section: Katp Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

259

347

View full text Add to dashboard Cite

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“…One possible explanation is that the hypotensive response to LCK was due to a fall in cardiac output as a result of a negative inotropic and/or venodilator action that was not influenced by a-trinositol. However, current evidence indicates LCK is devoid of such actions (Cavero et al, 1989;Hamilton et al, 1993). It is clear that a-trinositol was exerting selective effects on the mesenteric vasodilator responses to LCK, and these were apparent also with the middle dose of a-trinositol.…”

Section: Effects Of A-trinositol On Responses To Lckmentioning

confidence: 99%

Effects of glibenclamide on the regional haemodynamic actions of α‐trinositol and its influence on responses to vasodilators in conscious rats

Gardiner

Kemp

March

et al. 1996

British J Pharmacology

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1 In conscious rats, a-trinositol (D-myo-inositol-1, 2, 6 triphosphate; 5-80 mg kg-' h-' infusion) caused dose-dependent hypotension, tachycardia and hyperaemic dilatation in renal, mesenteric and hindquarters vascular beds. These effects were accompanied by inhibition of the renal vasodilator effects of acetylcholine (ACh), and of the mesenteric vasodilator effects of sodium nitroprusside (SNP) and, particularly, of levcromakalim (LCK).2 In the light of the latter finding, in a second experiment, we assessed the influence of the KATP channel inhibitor, glibenclamide (20 mg kg-'), on resting haemodynamics, on responses to ACh, bradykinin (BK), SNP and LCK, on the haemodynamic action of a-trinositol, and on the effects of the latter on responses to the vasodilators, over a period of 3 days. 3 In the presence of saline, glibenclamide caused a reproducible pressor effect, accompanied by renal, mesenteric, and hindquarters vasoconstrictions on all 3 experimental days; these effects were unrelated to changes in blood glucose. In the presence of glibenclamide, only the hindquarters vasodilator response to BK, and all the cardiovascular actions of LCK were inhibited. 4 On the first experimental day, the hindquarters vasodilator effect of cx-trinositol was substantially inhibited by glibenclamide, the renal vasodilatation less so, and the mesenteric vasodilatation not at all. However, over the subsequent two days, the mesenteric vasodilator effect of ac-trinositol became increasingly sensitive to glibenclamide. 5 In the presence of a-trinositol and glibenclamide, on the first experimental day, the inhibition of the renal vasodilator effect of ACh was no greater than with a-trinositol alone in the first experiment. Moreover, on the third experimental day, both before and after glibenclamide, the inhibition by atrinositol of the renal vasodilator response to ACh was less than on the first experimental day. Similarly, the a-trinositol-induced inhibition of the mesenteric vasodilator effect of SNP, and of the hindquarters vasodilator action of BK, waned over the 3 experimental days. The inhibition of the cardiovascular effects of LCK were similar on all 3 experimental days, but no greater in the presence of ax-trinositol and glibenclamide than with glibenclamide alone.6 These results indicate that KATP channels are involved in the maintenance of resting vasodilator tone in renal, mesenteric and hindquarters vascular beds. However, although additional activation of KATP channels is responsible for all the haemodynamic effects of LCK, it contributes only to the hindquarters vasodilator action of BK and is not involved in any of the responses to ACh or SNP. The hindquarters, renal and mesenteric vasodilator effects of a-trinositol may involve (in the same rank order) activation of KATP channels, probably through an indirect mechanism. However, it is unlikely that direct or indirect interaction of a-trinositol with KATP channels explains the ability of the drug to inhibit the renal vasodilator action of ACh, or the mesenteric v...

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“…Effects of levcromakalim (BRL 38227) on isolated guinea-pig detrusor smooth muscle (Hamilton et al 1993). These actions are believed to be mediated via opening of ATP-dependent K+ channels in such cells.…”

Section: Germanymentioning

confidence: 99%

Smooth Muscle Physiology

1995

The Journal of Physiology

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Levcromakalim

Cited by 15 publications

References 52 publications

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Effects of glibenclamide on the regional haemodynamic actions of α‐trinositol and its influence on responses to vasodilators in conscious rats

Smooth Muscle Physiology

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