Role of chloride in constriction of descending vasa recta by angiotensin II

2001 ◽  
Vol 280 (6) ◽  
pp. R1878-R1886 ◽  
Author(s):  
Zhong Zhang ◽  
James M. C. Huang ◽  
Malcolm R. Turner ◽  
Kristie L. Rhinehart ◽  
Thomas L. Pallone
Keyword(s):  
Membrane Potential ◽  
Chloride Channels ◽  
Channel Blocker ◽  
Chloride Ion ◽  
Ang Ii ◽  
Vasa Recta ◽  
Gramicidin D ◽  
Chloride Channel Blocker ◽  
Increased Activity

We investigated the dependence of ANG II (10−8 M)-induced constriction of outer medullary descending vasa recta (OMDVR) on membrane potential (Ψm) and chloride ion. ANG II depolarized OMDVR, as measured by fully loading them with the voltage-sensitive dye bis[1,3-dibutylbarbituric acid-(5)] trimethineoxonol [DiBAC4(3)] or selectively loading their pericytes. ANG II was also observed to depolarize pericytes from a resting value of −55.6 ± 2.6 to −26.2 ± 5.4 mV when measured with gramicidin D-perforated patches. When measured with DiBAC4(3) in unstimulated vessels, neither changing extracellular Cl− concentration ([Cl−]) nor exposure to the chloride channel blocker indanyloxyacetic acid 94 (IAA-94; 30 μM) affected Ψm. In contrast, IAA-94 repolarized OMDVR pretreated with ANG II. Neither IAA-94 (30 μM) nor niflumic acid (30 μM, 1 mM) affected the vasoactivity of unstimulated OMDVR, whereas both dilated ANG II-preconstricted vessels. Reduction of extracellular [Cl−] from 150 to 30 meq/l enhanced ANG II-induced constriction. Finally, we identified a Cl−channel in OMDVR pericytes that is activated by ANG II or by excision into extracellular buffer. We conclude that constriction of OMDVR by ANG II involves pericyte depolarization due, in part, to increased activity of chloride channels.

Control of descending vasa recta pericyte membrane potential by angiotensin II

2002 ◽  
Vol 282 (6) ◽  
pp. F1064-F1074 ◽  
Author(s):  
Thomas L. Pallone ◽  
James M.-C. Huang
Keyword(s):  
Membrane Potential ◽  
Angiotensin Ii ◽  
Reversal Potential ◽  
Niflumic Acid ◽  
Channel Blockers ◽  
Ang Ii ◽  
Vasa Recta ◽  
Cell Recording ◽  
Inward Currents

Using nystatin perforated-patch whole cell recording, we investigated the role of Cl−conductance in the modulation of outer medullary descending vasa recta (OMDVR) pericyte membrane potential (Ψm) by ANG II. ANG II (10−11 to 10−7 M) consistently depolarized OMDVR and induced Ψm oscillations at lower concentrations. The Cl− channel blockers anthracene-9-decarboxylate (1 mM) and niflumic acid (10 μM) hyperpolarized resting pericytes and repolarized ANG II-treated pericytes. In voltage-clamp experiments, ANG II-treated pericytes exhibited slowly activating currents that were nearly eliminated by treatment with niflumic acid (10 μM) or removal of extracellular Ca2+. Those currents reversed at −31 and −10 mV when extracellular Cl− concentration was 152 and 34 mM, respectively. In pericytes held at −70 mV, oscillating inward currents were sometimes observed; the reversal potential also shifted with extracellular Cl− concentration. We conclude that ANG II activates a Ca2+-dependent Cl− conductance in OMDVR pericytes to induce membrane depolarization and Ψm oscillations.

Membrane potential controls calcium entry into descending vasa recta pericytes

2002 ◽  
Vol 283 (4) ◽  
pp. R949-R957 ◽  
Author(s):  
Zhong Zhang ◽  
Kristie Rhinehart ◽  
Thomas L. Pallone
Keyword(s):  
Membrane Potential ◽  
Channel Blocker ◽  
Calcium Entry ◽  
Ang Ii ◽  
Channel Blockade ◽  
Voltage Gated ◽  
Vasa Recta ◽  
Intracellular Ca ◽  
Bayk 8644

We tested the hypothesis that constriction of descending vasa recta (DVR) is mediated by voltage-gated calcium entry. K+ channel blockade with BaCl2 (1 mM) or TEACl (30 mM) depolarized DVR smooth muscle/pericytes and constricted in vitro-perfused vessels. Pericyte depolarization by 100 mM extracellular KCl constricted DVR and increased pericyte intracellular Ca2+ ([Ca2+]i). The KATP channel opener pinacidil (10−7-10−4 M) hyperpolarized resting pericytes, repolarized pericytes previously depolarized by ANG II (10−8 M), and vasodilated DVR. The DVR vasodilator bradykinin (10−7 M) also reversed ANG II depolarization. The L-type Ca2+ channel blocker diltiazem vasodilated ANG II (10−8 M)- or KCl (100 mM)-preconstricted DVR, and the L-type agonist BayK 8644 constricted DVR. The plateau phase of the pericyte [Ca2+]i response to ANG II was inhibited by diltiazem. These data support the conclusion that DVR vasoreactivity is controlled through variation of membrane potential and voltage-gated Ca2+ entry into the pericyte cytoplasm.

Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles

1996 ◽  
Vol 270 (5) ◽  
pp. F718-F727 ◽  
Author(s):  
B. L. Jensen ◽  
O. Skott
Keyword(s):  
Angiotensin Ii ◽  
Chloride Channels ◽  
Channel Blocker ◽  
Inhibitory Effect ◽  
Renin Release ◽  
Disulfonic Acid ◽  
Basal Diameter ◽  
Chloride Channel Blocker ◽  
Afferent Arterioles ◽  
Dose Dependent

Calcium-activated chloride channels have been proposed to control renin release from juxtaglomerular cells and to be involved in the excitation-contraction coupling of the renal afferent arteriole. The hypothesis was tested on renin release from rat glomeruli and in microperfused rabbit afferent arterioles with the chloride channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Renin secretion was equally enhanced by omission of extracellular calcium and by addition of 0.5 mM DIDS. The inhibitory effect of calcium was blocked by DIDS. The stimulatory effects of low calcium [with or without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was suppressed and the stimulatory effect of DIDS was abolished. The DIDS-induced enhancement of renin release was not dependent on bicarbonate. Norepinephrine (5 x 10(-7)-1 x 10(-6) M) and angiotensin II (1 x 10(-8)-10(-6) M) evoked reversible and dose-dependent contractions of microperfused rabbit afferent arterioles. DIDS (0.5 mM) did not affect the basal diameter of the arterioles but strongly inhibited the response to angiotensin II and attenuated the duration of the contractile response to norepinephrine. The results support the hypothesis that DIDS-sensitive calcium-activated chloride channels are involved in regulation of renin release and in the afferent arteriolar contraction after angiotensin II but do not play a pivotal role in the response to norepinephrine.

Functional role of sodium-calcium exchange in the regulation of renal vascular resistance

2001 ◽  
Vol 280 (1) ◽  
pp. F155-F161 ◽  
Author(s):  
Frank Schweda ◽  
Helga Seebauer ◽  
Bernhard K. Krämer ◽  
Armin Kurtz
Keyword(s):  
Calcium Channels ◽  
Vascular Resistance ◽  
Functional Role ◽  
Channel Blocker ◽  
Sodium Concentration ◽  
Renal Vascular Resistance ◽  
Partial Replacement ◽  
Chloride Channel Blocker ◽  
Renal Vascular

Our study aimed to assess a possible functional role of the Na+/Ca2+ exchanger in the regulation of renal vascular resistance (RVR). Therefore, we investigated the effects of an inhibition of the Na+/Ca2+ exchanger either by lowering the extracellular sodium concentration ([Na+]e) or, pharmacologically on RVR, by using isolated perfused rat kidneys. Graded decreases in [Na+]e led to dose-dependent increases in RVR to 4.3-fold (35 mM Na+). This vasoconstriction was markedly attenuated by lowering the extracellular calcium concentration, by the L-type calcium channel blocker amlodipine or by the chloride channel blocker niflumic acid. Further lowering of [Na+]e to 7 mM led to an increase in RVR to 7.5-fold. In this setting, amlodipine did not influence the magnitude but did influence the velocity of vasoconstriction. Pharmacological blockade of the Na+/Ca2+ exchanger with KB-R7943, benzamil, or nickel resulted in significant vasoconstriction (RVR 2.5-, 1.8-, and 4.2-fold of control, respectively). Our data suggest a functional role of the Na+/Ca2+ exchanger in the renal vascular bed. In conditions of partial replacement of [Na+]e, vasoconstriction is dependent on chloride and L-type calcium channels. A total replacement of [Na+]e leads to a vasoconstriction that is nearly independent of L-type calcium channels. This might be due to an active calcium transport into the cell by the Na+/Ca2+ exchanger.

Inhibition of K+ conductance in descending vasa recta pericytes by ANG II

2004 ◽  
Vol 287 (6) ◽  
pp. F1213-F1222 ◽  
Author(s):  
Thomas L. Pallone ◽  
Chunhua Cao ◽  
Zhong Zhang
Keyword(s):  
Membrane Potential ◽  
Resting Membrane Potential ◽  
Minor Effect ◽  
Channel Blockers ◽  
Ang Ii ◽  
Channel Inhibition ◽  
Outward Currents ◽  
Vasa Recta ◽  
A Minor ◽  
Contrast Reduction

We tested whether K+ channel inhibition accompanies ANG II-induced depolarization of descending vasa recta (DVR) pericytes. An increase in extracellular K+ concentration ([K+]o) from 5 to 100 mM depolarized resting pericytes but had no effect after prolonged (10 nM, 20 min) ANG II exposure. In contrast, reduction of extracellular Cl− concentration ([Cl−]o) from 154 to 34 mM had a minor effect on resting membrane potential but strongly depolarized pericytes treated with ANG II. The K+ channel blockers BaCl2 (0.1, 1 mM) and tetraethylammonium (TEA; 30 mM) depolarized resting pericytes but did not affect membrane potential of ANG II-treated pericytes. Pericyte whole cell currents were reduced by ANG II and nearly eliminated by combined ANG II exposure and the Cl− channel blocker niflumic acid (100 μM). Augmentation of inward current induced by raising [K+]O from 5 to 50 mM was eliminated by preexposure to ANG II. TEA- and BaCl2-sensitive outward currents, generated by depolarizing pericytes from −80 to −40 mV, were eliminated by ANG II. We conclude that ANG II depolarizes DVR pericytes by a combination of Cl− channel activation and K+ channel inhibition.

Dihydropyridine-sensitive initial component of the ANG II-induced Ca2+ response in rat adrenal glomerulosa cells

1994 ◽  
Vol 266 (1) ◽  
pp. C67-C72 ◽  
Author(s):  
L. Hunyady ◽  
T. Rohacs ◽  
A. Bago ◽  
F. Deak ◽  
A. Spat
Keyword(s):  
Initial Phase ◽  
Channel Blocker ◽  
Lag Time ◽  
Ang Ii ◽  
Slow Kinetics ◽  
Glomerulosa Cells ◽  
K Concentration ◽  
Kinetics Of ◽  
Peak Phase

The Ca2+ signal induced by an increase in extracellular K+ concentration from 3.6 to 5.6 mM or angiotensin II (ANG II) was inhibited by the dihydropyridine (DHP) Ca2+ channel blocker, nifedipine, and enhanced by the DHP Ca2+ channel agonist, BAY K 8644. The DHP sensitivity of the ANG II-induced Ca2+ response was already detectable during the peak phase, suggesting that the DHP receptor plays an important role during the initial phase of ANG II stimulation. K+ and ANG II stimulated a nifedipine-sensitive Mn2+ influx pathway, further promoting the role of a DHP receptor in their mechanism of action. Fluorescent membrane potential measurements showed that, in contrast to the rapid depolarization induced by K+, the ANG II-induced depolarization had a lag time of > 30 s. The slow kinetics of depolarization compared with the immediate effect of ANG II on Mn2+ influx and the DHP sensitivity of the initial Ca2+ peak indicates that ANG II initiates the activation of the DHP-sensitive Ca2+ channel by a mechanism other than depolarization.

Reduced expression of SKCa and IKCa channel proteins in rat small mesenteric arteries during angiotensin II-induced hypertension

2007 ◽  
Vol 292 (5) ◽  
pp. H2275-H2284 ◽  
Author(s):  
Rob H. P. Hilgers ◽  
R. Clinton Webb
Keyword(s):  
Angiotensin Ii ◽  
Channel Blocker ◽  
Mesenteric Arteries ◽  
Ang Ii ◽  
Expression Levels ◽  
Protein Levels ◽  
Channel Proteins ◽  
Induced Hypertension ◽  
Relaxation Responses

Ca2+-activated K+ channels (KCa), in particular, the small and intermediate KCa (SKCa and IKCa, respectively) channels, are key players in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in small arteries. Hypertension is characterized by an endothelial dysfunction, possibly via reduced EDHF release and/or function. We hypothesize that during angiotensin II (14 days)-induced hypertension (ANG II-14d), the contribution of SKCa and IKCa channels in ACh-induced relaxations is reduced due to decreased expression of SKCa and IKCa channel proteins in rat small mesenteric arteries (MAs). Nitric oxide- and prostacyclin-independent vasorelaxation to ACh was similar in small MAs of sham-operated and ANG II-14d rats. Catalase had no inhibitory effects on these relaxations. The highly selective SKCa channel blocker UCL-1684 almost completely blocked these responses in MAs of sham-operated rats but partially in MAs of ANG II-14d rats. These changes were pressure dependent since UCL-1684 caused a greater inhibition in MAs of 1-day ANG II-treated normotensive rats compared with ANG II-14d rats. Expression levels of both mRNA and protein SK3 were significantly reduced in MAs of ANG II-14d rats. The IKCa channel blocker 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) resulted in comparable reductions in the relaxation responses to ACh in MAs of sham-operated and ANG II-14d rats. Relative mRNA expression levels of IK1 were significantly reduced in MAs of ANG II-14d rats, whereas protein levels of IK1 were not but tended to be lower in MAs of ANG II-14d rats. The findings demonstrate that EDHF-like responses are not compromised in a situation of reduced functional activity and expression of SK3 channels in small MAs of ANG II-induced hypertensive rats. The role of IK1 channels is less clear but might compensate for reduced SK3 activity.

Ca2+ signaling and membrane potential in descending vasa recta pericytes and endothelia

2002 ◽  
Vol 283 (4) ◽  
pp. F852-F860 ◽  
Author(s):  
Kristie Rhinehart ◽  
Zhong Zhang ◽  
Thomas L. Pallone
Keyword(s):  
Membrane Potential ◽  
Enzymatic Digestion ◽  
Ang Ii ◽  
Cell Type ◽  
Potential Measurement ◽  
Fura 2 ◽  
Vasa Recta ◽  
Cell Recording ◽  
Intracellular Ca ◽  
Inside Out

We devised a method for removal of pericytes from isolated descending vasa recta (DVR). After enzymatic digestion, aspiration of a descending vas rectum into a micropipette strips the pericytes from the abluminal surface. Pericytes and denuded endothelia can be recovered for separate study. Using fura 2-loaded preparations, we demonstrated that 10 nM angiotensin II (ANG II) elevates pericyte intracellular Ca2+ concentration ([Ca2+]i) and suppresses endothelial [Ca2+]i. The anion transport blocker probenecid helps retain fura 2 in the pericyte cytoplasm. DVR endothelia were accessed for membrane potential measurement by perforated-patch whole cell recording by using the pericyte-stripping technique and by turning nondigested vessels inside out with concentric micropipettes. By either method of access, 10 nM ANG II depolarized ( n = 20) and 100 nM bradykinin hyperpolarized ( n = 25) the endothelia. We conclude that isolated endothelia and pericytes remain functional for study of [Ca2+]i responses and that ANG II and bradykinin receptors exist separately on each cell type.

Role of large Ca(2+)-activated K+ channels in regulation of mesangial contraction by nitroprusside and ANP

1996 ◽  
Vol 270 (6) ◽  
pp. C1773-C1779 ◽  
Author(s):  
J. D. Stockand ◽  
S. C. Sansom
Keyword(s):  
Membrane Potential ◽  
Guanylyl Cyclase ◽  
Specific Inhibitor ◽  
Equilibrium Potential ◽  
Bathing Solution ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
K Channels ◽  
Baseline Activity

The patch-clamp method, in conjunction with measurements of cell contraction, was employed to investigate activation by guanosine 3',5'-cyclic monophosphate (cGMP) and guanylyl cyclase-stimulating vasodilators of large Ca(2+)-activated K+ channels (BKCa) in human glomerular mesangial cells (MC). In cell-attached patches, with physiological NaCl bathing solutions, BKCa was activated transiently by nitroprusside [NP; a nitric oxide (NO) donor], atrial natriuretic peptide (ANP), and dibutyryl cGMP (DBcGMP), reaching peak responses between 10 and 60 s and decreasing to near baseline activity within the next 120 s. In the presence of LY-83583, a specific inhibitor of guanylyl cyclase, BKCa was activated on cell by DBcGMP but not by NP or ANP. In all cases, the increase in channel activity coincided with a decrease in channel amplitude, indicating that the membrane potential was approaching equilibrium potential as BKCa was activated. If membrane potential was maintained depolarized with 140 mM KCl in the bathing solution, DBcGMP induced a sustained activation of BKCa. In the continued presence of DBcGMP, BKCa was further activated when 100 nM angiotensin II (ANG II) was added to the bathing solution. Experiments were performed to determine the role of BKCa in the regulation by vasorelaxants of mesangial contraction measured as percent maximal and defined by reduction in length induced by replacing 135 mM bath NaCl with KCl. Contraction by ANG II (100 nM = 60.5%) was attenuated by NP (100 microM), ANP (1.0 microM), and DBcGMP (10 microM) in the absence, but not the presence, of iberiotoxin, a specific inhibitor of BKCa. These results indicate that guanylyl cyclase-stimulating vasorelaxants counteract ANG II-induced contraction of MC, in part, by repolarizing the membrane through activation of BKCa channels.

Role of kinins and angiotensin II in the renal hemodynamic response to captopril

1991 ◽  
Vol 260 (5) ◽  
pp. F670-F679 ◽  
Author(s):  
D. L. Mattson ◽  
R. J. Roman
Keyword(s):  
Angiotensin Ii ◽  
Wistar Rats ◽  
Plasma Renin ◽  
Hemodynamic Response ◽  
Ang Ii ◽  
Peritubular Capillary ◽  
Renal Hemodynamic ◽  
Vasa Recta ◽  
Capillary Pressures

This study examined the role of angiotensin II (ANG II), kinins, and prostaglandins in the renal hemodynamic response to captopril in Munich-Wistar rats in which plasma renin activity was elevated [18.8 +/- 3.3 ng angiotensin I (ANG I).ml-1.h-1]. Neural influences on the kidney were eliminated by renal denervation, and renal perfusion pressure (RPP) was controlled using a clamp on the aorta. Urine flow, sodium excretion, renal blood flow (RBF), glomerular filtration rate (GFR), and cortical and papillary red blood cell (RBC) flow increased significantly after captopril (2 mg/kg iv). Glomerular and peritubular capillary pressures rose by 20%, and vasa recta capillary pressure fell by 3-4 mmHg due to significant reductions in estimated preglomerular, efferent arteriolar and renal capillary-venous vascular resistances. Infusion of ANG II (20 ng.kg-1.min-1 iv) returned RBF, GFR, and glomerular and peritubular capillary pressures to control; however, ANG II did not lower papillary RBC flow before inhibition of prostaglandin synthesis. Saralasin had no effect on papillary RBC flow or the response to captopril. The changes in vasa recta hemodynamics produced by captopril were blocked by a kinin antagonist. These findings indicate that ANG II exerts a vasoconstrictor influence on the renal cortical vasculature of Munich-Wistar rats; however, its effects on the medullary circulation are opposed by vasodilatory eicosanoids. They also suggest that kinins participate in the papillary RBC flow response to captopril, perhaps by reducing the outflow resistance from the vasa recta circulation.

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