Sympathetic neurogenic Ca²⁺ signalling in rat arteries: ATP, noradrenaline and neuropeptide Y

Abstract

The sympathetic nervous system (SNS) plays an essential role in the control of total peripheral vascular resistance by controlling the contraction of small arteries. The SNS also exerts long-term trophic influences in health and disease; SNS hyperactivity accompanies most forms of human essential hypertension, obesity and heart failure. 2+ signals, electrical recording of excitatory junction potentials and carbon fibre amperometry to measure NA, varies markedly with the pattern of nerve activity. This probably reflects both pre-and postjunctional mechanisms, which are not yet fully understood. These phenomena, together with different temporal patterns of sympathetic nerve activity in different regional circulations, are probably an important mechanistic basis of the important selective regulation of regional vascular resistance and blood flow by the sympathetic nervous system.

Ca2+ entry following P2X receptor activation induces IP3 receptor‐mediated Ca2+ release in myocytes from small renal arteries

“…The initial Ca 2+ mobilization may be augmented by RyR-mediated Ca 2+ release recruited via a CICR mechanism (Bolton and Gordienko, 1998;Bayguinov et al, 2000;White and McGeown, 2002;Kotlikoff, 2003;Zhang et al, 2003;Hotta et al, 2007;Gordienko et al, 2008). The contribution of these mechanisms to intracellular Ca 2+ mobilization may vary in different SMC types, depending on the type and strength of stimuli, SMC excitability and spatial organisation of intracellular Ca 2+ release units (Walsh, 1994;Bolton and Gordienko, 1998;Bolton et al, 1999;Davis and Hill, 1999;Bayguinov et al, 2000;Gordienko et al, 2001Gordienko et al, , 2008Janiak et al, 2001;Gordienko and Bolton, 2002;White and McGeown, 2002;Kotlikoff, 2003;Wier and Morgan, 2003;Zhang et al, 2003;Lamont and Wier, 2004;McCarron et al, 2006;Amberg et al, 2007;Hotta et al, 2007;Wier et al, 2009).…”

“…Two major sympathetic cotransmitters, noradrenaline and ATP, mediate vasoconstriction of small arteries (Wier et al, 2009) by acting on metabotropic a1-adrenoceptors and ionotropic P2X receptors respectively. Thus, P2X receptors provide an important therapeutic target, mediating substantial vasoconstrictor drive resistant to adrenoceptor antagonists (Wier et al, 2009).…”

“…The ability of Ca 2+ liberated via IP3Rs to trigger RyR-mediated Ca 2+ release also varies among different types of smooth muscles and depends on receptor distribution and isoform expression (reviewed in Wray and Burdyga, 2010 Two major sympathetic cotransmitters, noradrenaline and ATP, mediate vasoconstriction of small arteries (Wier et al, 2009) by acting on metabotropic a1-adrenoceptors and ionotropic P2X receptors respectively. Thus, P2X receptors provide an important therapeutic target, mediating substantial vasoconstrictor drive resistant to adrenoceptor antagonists (Wier et al, 2009).…”

“…The initial Ca 2+ mobilization may be augmented by RyR-mediated Ca 2+ release recruited via a CICR mechanism (Bolton and Gordienko, 1998;Bayguinov et al, 2000;White and McGeown, 2002;Kotlikoff, 2003;Zhang et al, 2003;Hotta et al, 2007;Gordienko et al, 2008). The contribution of these mechanisms to intracellular Ca 2+ mobilization may vary in different SMC types, depending on the type and strength of stimuli, SMC excitability and spatial organisation of intracellular Ca 2+ release units (Walsh, 1994;Bolton and Gordienko, 1998;Bolton et al, 1999;Davis and Hill, 1999;Bayguinov et al, 2000;Gordienko et al, 2001Gordienko et al, , 2008Janiak et al, 2001;Gordienko and Bolton, 2002;White and McGeown, 2002;Kotlikoff, 2003;Wier and Morgan, 2003;Zhang et al, 2003;Lamont and Wier, 2004;McCarron et al, 2006;Amberg et al, 2007;Hotta et al, 2007;Wier et al, 2009).We hypothesized that in vascular myocytes Ca 2+ entry following activation of ionotropic P2X receptors may induce IP3R-mediated Ca 2+ release. Our hypothesis was based on the following findings reported in visceral and vascular myocytes: (i) a localized increase in [Ca 2+ ]i induced by local flash release of Ca 2+ from a 'caged' precursor may trigger IP3R-mediated Ca 2+ release (Ji et al, 2006); (ii) Ca 2+ entry via VGCCs facilitates IP3R-mediated Ca 2+ release following stimulation of metabotropic receptors (Gordienko et al, 2008); (iii) the stoichiometric ratio of RyRs to IP3Rs in SMCs is 1:9-10, suggesting the existence of a Ca 2+ -storage compartment devoid of RyRs but equipped with IP3Rs (Wibo and Godfraind, 1994); (iv) caffeine/ryanodinereleasable and IP3-releasable calcium stores in the SR of vascular myocytes are at least partially distinct with about 56% of the SR being solely IP3-sensitive (Blauste...…”

“…The ability of Ca 2+ liberated via IP3Rs to trigger RyR-mediated Ca 2+ release also varies among different types of smooth muscles and depends on receptor distribution and isoform expression (reviewed in Wray and Burdyga, 2010 Two major sympathetic cotransmitters, noradrenaline and ATP, mediate vasoconstriction of small arteries (Wier et al, 2009) by acting on metabotropic a1-adrenoceptors and ionotropic P2X receptors respectively. Thus, P2X receptors provide an important therapeutic target, mediating substantial vasoconstrictor drive resistant to adrenoceptor antagonists (Wier et al, 2009).In the kidney, apart from sympathetic transmission, ATP is involved in paracrine regulation. On being released by apical macula densa cells in response to an increase in NaCl concentration in the distal tubular fluid (Bell et al, 2003), ATP triggers P2X receptor-mediated vasoconstriction of afferent arterioles (Inscho et al, 2003), thus decreasing RBF and glomerular filtration rate.…”