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      Chloride Channel Blockade Attenuates the Effect of Angiotensin II on Tubuloglomerular Feedback in WKY but not Spontaneously Hypertensive Rats

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          Recent studies have shown that calcium-dependent chloride channels may play a crucial role in the modulation of the vascular effects of angiotensin II (ANG II). Thus, alterations in the function of these channels may be responsible for the enhanced renal vasoconstrictor and tubuloglomerular feedback (TGF) response to ANG II in spontaneously hypertensive rats (SHR). We investigated the effect of the calcium-dependent chloride channel blocker IAA-94 on renal hemodynamics and TGF responses. The renal interstitium was perfused with control solution, with ANG II, and with both ANG II and IAA-94. In Wistar Kyoto rats (WKY), perfusion with ANG II significantly increased renal vascular resistance (RVR), but the effect was significantly attenuated by perfusion with ANG II/IAA-94. In SHR, ANG II caused a significant elevation of RVR that was not altered by the simultaneous infusion of IAA-94. Proximal tubular stop flow pressure (P<sub>sf</sub>) was monitored during perfusion of peritubular capillaries with control solution, and subsequently with IAA-94, ANG II or both ANG II and IAA-94. TGF response magnitude of WKY rats was significantly augmented with ANG II, and this effect was suppressed by perfusion with ANG II /IAA-94. However, in SHR peritubular perfusion with ANG II/IAA-94 did not suppress the TGF response. We conclude that chloride channels susceptible to IAA-94 may play a significant role in modulating the effects of ANG II on renal hemodynamics, and that this modulation is absent in SHR.

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          Most cited references 3

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          Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors.

          Adenosine is a determinant of metabolic control of organ function increasing oxygen supply through the A2 class of adenosine receptors and reducing oxygen demand through A1 adenosine receptors (A1AR). In the kidney, activation of A1AR in afferent glomerular arterioles has been suggested to contribute to tubuloglomerular feedback (TGF), the vasoconstriction elicited by elevations in [NaCl] in the macula densa region of the nephron. To further elucidate the role of A1AR in TGF, we have generated mice in which the entire A1AR coding sequence was deleted by homologous recombination. Homozygous A1AR mutants that do not express A1AR mRNA transcripts and do not respond to A1AR agonists are viable and without gross anatomical abnormalities. Plasma and urinary electrolytes were not different between genotypes. Likewise, arterial blood pressure, heart rates, and glomerular filtration rates were indistinguishable between A1AR(+/+), A1AR(+/-), and A1AR(-/-) mice. TGF responses to an increase in loop of Henle flow rate from 0 to 30 nl/min, whether determined as change of stop flow pressure or early proximal flow rate, were completely abolished in A1AR(-/-) mice (stop flow pressure response, -6.8 +/- 0.55 mmHg and -0.4 +/- 0.2 in A1AR(+/+) and A1AR(-/-) mice; early proximal flow rate response, -3.4 +/- 0.4 nl/min and +0.02 +/- 0.3 nl/min in A1AR(+/+) and A1AR(-/-) mice). Absence of TGF responses in A1AR-deficient mice suggests that adenosine is a required constituent of the juxtaglomerular signaling pathway. A1AR null mutant mice are a promising tool to study the functional role of A1AR in different target tissues.
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            Calcium response to adenosine and ATP in rabbit afferent arterioles

             GUTIÉRREZ,  Kornfeld,  Persson (1999)
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              Effects of Cytosolic Ca2+on Membrane Voltage and Conductance of Cultured Mesangial Cells from Stroke-Prone Spontaneously Hypertensive Rats and WKY Rats


                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                July 2004
                02 February 2004
                : 27
                : 1
                : 35-42
                aDepartment of Internal Medicine II, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan; bNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, MSC 1370, Bethesda,Md., USA
                75621 Kidney Blood Press Res 2004;27:35–42
                © 2004 S. Karger AG, Basel

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                Figures: 4, Tables: 1, References: 28, Pages: 8
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