Signaling Mechanisms Underlying the Vascular Myogenic Response

Abstract

The vascular myogenic response refers to the acute reaction of a blood vessel to a change in transmural pressure. This response is critically important for the development of resting vascular tone, upon which other control mechanisms exert vasodilator and vasoconstrictor influences. The purpose of this review is to summarize and synthesize information regarding the cellular mechanism(s) underlying the myogenic response in blood vessels, with particular emphasis on arterioles. When necessary, experiments performed on larger blood vessels, visceral smooth muscle, and even striated muscle are cited. Mechanical aspects of myogenic behavior are discussed first, followed by electromechanical coupling mechanisms. Next, mechanotransduction by membrane-bound enzymes and involvement of second messengers, including calcium, are discussed. After this, the roles of the extracellular matrix, integrins, and the smooth muscle cytoskeleton are reviewed, with emphasis on short-term signaling mechanisms. Finally, suggestions are offered for possible future studies.

Myogenic tone in mouse mesenteric arteries: evidence for P2Y receptor-mediated, Na+, K+, 2Cl− cotransport-dependent signaling

“…Indeed, the transient kinetics of ATP-induced contractions followed by prolonged inactivation of this signaling pathway (Fig. 2) are consistent with rapid decay of ATP-induced cation current detected in cells transfected with P2X 1 and P2X 3 but not other P2X isoforms [41,42]. Significantly, ATPinduced contractions were sharply suppressed by NF023, a compound that inhibited ion currents mediated by cloned P2X 1 and P2X 3 with IC 50 of 0.2 and 8 μM, respectively, but did not affect the activity of the other P2 receptors [14].…”

“…Unlike ATP, UTP activates P2Y 6 Gq/G 11 -coupled receptors that, in turn, evoke Ca 2+ release from the endoplasmic reticulum and activation of protein kinase C (PKC). Ca 2+ release from the endoplasmic reticulum elicits activation of Cl − channels, plasma membrane depolarization and activation of long-lasting L-type Ca 2+ channels, whose involvement in MT is well-documented in an overwhelming number of vessels studied so far [3]. Significantly, NKCC inhibition partially blocked the depolarizing action of Cl − channel activation via attenuation of [Cl -] i , as demonstrated in bumetanide-and furosemidetreated smooth muscle cells of different origins [20][21][22], and resulted in the MT suppression documented here (Fig.…”

“…6). Side-by-side with the [Ca 2+ ] i signaling precipitated by P2Y 6 receptors, MT may involve PKC activation that, in turn, leads to heightened [Ca 2+ ] i sensitivity of the contractile machinery via myosin light chain kinase phosphorylation [3].…”

The Proteome of Mouse Cerebral Arteries

“…21 Binding of IP3 to sarcoplasmic reticulum surface receptors (IP3Rs or ITPRs) activates Ca 2 þ release. 26 We detected three ITPRs, namely ITPR1, 2, and 3, all previously showed to be present in rat cerebral artery SMCs with ITPR1 being the most abundant. 27 In addition, the second messenger 1,2-diacylglycerol has been shown to activate PKC, which in turn increases smooth muscle contractility via several different mechanisms such as MLCP inhibition and increased actin availability.…”

Characterisation of glucose transporters in the intact coronary artery endothelium in rats: GLUT-2 upregulated by long-term hyperglycaemia

“…The role and function of endothelial cells varies between vascular beds: in capillaries, endothelial cells regulate gas and nutrient exchange or prevent the passage of harmful substances; while in larger vessels they also control vascular tone by releasing vasoconstrictors and vasodilators [1]. In small contractile vessels deprived of the vasa vasorum (small blood vessels irrigating the walls of large blood vessels), such as coronary arteries, the endothelial cells must allow transport between the blood and the cells of the vascular wall, but they must also protect the vessel's integrity through selective permeability.…”