Calcium activation mechanisms in the renal microvascular response to extracellular ATP

Abstract

Previous studies have suggested a paracrine role for extracellular ATP in the regulation of afferent arteriolar tone. The current study was conducted to determine the dependence of this response on calcium entry mechanisms. Experiments were performed in vitro using the blood-perfused juxtamedullary nephron technique combined with video microscopy. The afferent arteriolar response to alpha, beta-methylene ATP was determined before and after treatment with the calcium channel blockers, diltiazem or felodipine. alpha, beta-Methylene ATP was used to obviate concerns over responses being elicited by ATP or by ATP hydrolysis products such as adenosine. Previous studies have shown that afferent arteriolar responses to alpha, beta-methylene ATP are comparable to those elicited by ATP. alpha, beta-Methylene ATP (1.0 microM) induced a rapid initial afferent vasoconstriction of 72.5 +/- 10.6%, which partially recovered to a stable diameter 11.3 +/- 1.7% smaller than control (P < 0.01 vs control). Afferent diameter returned to control diameter on removal of ATP from the bath. Diltiazem or felodipine treatment significantly increased afferent diameter by 5.6 +/- 2.3 and 16.4 +/- 4.6%, respectively (P < 0.05). In the presence of either diltiazem or felodipine, the initial vasoconstriction to alpha, beta-methylene ATP was attenuated, and the sustained vasoconstriction was completely blocked. Removal of calcium from the extracellular medium completely abolished both the initial and sustained vasoconstrictor response.(ABSTRACT TRUNCATED AT 250 WORDS)

P2X Receptor-Stimulated Calcium Responses in Preglomerular Vascular Smooth Muscle Cells Involves 20-Hydroxyeicosatetraenoic Acid

“…ATP-mediated afferent arteriolar vasoconstriction is largely dependent on the influx of extracellular Ca 2ϩ and the sustained vasoconstriction is maintained by Ca 2ϩ influx through voltage-dependent L-type Ca 2ϩ channels (Inscho et al, 1995(Inscho et al, , 1999aNavar et al, 1996;Inscho and Cook, 2002). P2 receptor activation results in the release of arachidonic acid from membrane phospholipids in glomerular mesangial cells and rat astrocytes (Pfeilschifter, 1990; Schulze-Lohoff et al, Bolego et al, 1997).…”

“…ATP induces vasoconstriction by activating P2 receptors on preglomerular microvascular smooth muscle cells (Inscho et al, 1995(Inscho et al, , 1998Eltze and Ullrich, 1996). This vasoconstriction seems to depend on activation of P2X and P2Y receptors.…”

“…This vasoconstriction seems to depend on activation of P2X and P2Y receptors. ATP-mediated afferent arteriolar vasoconstriction is largely dependent on the influx of extracellular Ca 2ϩ , and the sustained vasoconstriction is maintained by Ca 2ϩ influx through voltage-dependent L-type Ca 2ϩ channels (Inscho et al, 1995(Inscho et al, , 1999bNavar et al, 1996;Inscho and Cook, 2002). Activation of P2X and P2Y receptors on microvascular smooth muscle cells stimulates an increase in intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) by distinct Ca 2ϩ signaling pathways (Inscho et al, 1999a,b).…”

12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels

“…The L-type calcium channel inhibitor, diltiazem, abolished the afferent arteriolar constriction elicited by 12(S)-HETE. Diltiazem was administered at a dose that completely blocks KCl-mediated afferent arteriolar constriction (35). These initial functional studies suggest that L-type calcium channel activation contributes to the 12(S)-HETE-mediated constrictor response.…”

Regulation of Renal Hemodyamics by Purinergic Receptors in Angiotensin II -Induced Hypertension

“…In the isolated juxtamedullary nephron preparation, ATP induces an initial vasoconstriction of the afferent arterioles (Inscho et al, 1995;Inscho et al,1996) that wanes and finally remains a residual vasoconstriction, as observed in "in vivo" studies; the blockade of adenosine receptors increases the ATP-mediated vasoconstriction. The ATP vasoconstrictor effect was maintained during the blockade of nitric oxide, supporting the notion that stimulation of P2Yreceptors induce an initial vasoconstriction that is counterbalanced by a later NO release, resulting in a transient vasoconstriction induced by ATP (Inscho et al, 1994).…”