scholarly journals Potassium channel contributions to afferent arteriolar tone in normal and diabetic rat kidney

2008 ◽  
Vol 295 (1) ◽  
pp. F171-F178 ◽  
Author(s):  
Carmen M. Troncoso Brindeiro ◽  
Rachel W. Fallet ◽  
Pascale H. Lane ◽  
Pamela K. Carmines
Keyword(s):  
Potassium Channel ◽  
Rat Kidney ◽  
The Other ◽  
Diabetic Rat ◽  
Channel Blockers ◽  
Juxtamedullary Nephron ◽  
Afferent Arterioles ◽  
Arteriolar Tone ◽  
Constrictor Response

We previously reported an enhanced tonic dilator impact of ATP-sensitive K+ channels in afferent arterioles of rats with streptozotocin (STZ)-induced diabetes. The present study explored the hypothesis that other types of K+ channel also contribute to afferent arteriolar dilation in STZ rats. The in vitro blood-perfused juxtamedullary nephron technique was utilized to quantify afferent arteriolar lumen diameter responses to K+ channel blockers: 0.1–3.0 mM 4-aminopyridine (4-AP; KV channels), 10–100 μM barium (KIR channels), 1–100 nM tertiapin-Q (TPQ; Kir1.1 and Kir3.x subfamilies of KIR channels), 100 nM apamin (SKCa channels), and 1 mM tetraethylammonium (TEA; BKCa channels). In kidneys from normal rats, 4-AP, TEA, and Ba2+ reduced afferent diameter by 23 ± 3, 8 ± 4, and 18 ± 2%, respectively, at the highest concentrations employed. Neither TPQ nor apamin significantly altered afferent diameter. In arterioles from STZ rats, a constrictor response to TPQ (22 ± 4% decrease in diameter) emerged, and the response to Ba2+ was exaggerated (28 ± 5% decrease in diameter). Responses to the other K+ channel blockers were similar to those observed in normal rats. Moreover, exposure to either TPQ or Ba2+ reversed the afferent arteriolar dilation characteristic of STZ rats. Acute surgical papillectomy did not alter the response to TPQ in arterioles from normal or STZ rats. We conclude that 1) KV, KIR, and BKCa channels tonically influence normal afferent arteriolar tone, 2) KIR channels (including Kir1.1 and/or Kir3.x) contribute to the afferent arteriolar dilation during diabetes, and 3) the dilator impact of Kir1.1/Kir3.x channels during diabetes is independent of solute delivery to the macula densa.

T-type calcium channels in the regulation of afferent and efferent arterioles in rats

2004 ◽  
Vol 286 (2) ◽  
pp. F331-F337 ◽  
Author(s):  
Ming-Guo Feng ◽  
Ming Li ◽  
L. Gabriel Navar
Keyword(s):  
Perfusion Pressure ◽  
Channel Blockers ◽  
Channel Blockade ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Arteriolar Resistance ◽  
Afferent Arterioles ◽  
Constrictor Response

L-type Ca2+ channels predominantly influence preglomerular arterioles, but there is less information regarding the role of T-type Ca2+ channels in regulating the renal microvasculature. We compared the effects of T- and L-type channel blockade on afferent and efferent arterioles using the in vitro blood-perfused juxtamedullary nephron preparation. Single afferent or efferent arterioles of Sprague-Dawley rats were visualized and superfused with solutions containing Ca2+ channel blockers. We confirmed that L-type channel blockade with diltiazem dilates afferent arterioles but has no significant effects on efferent arterioles. In contrast, T-type channel blockade with pimozide (10 μmol/l) or mibefradil (1 μmol/l) dilated both afferent (26.8 ± 3.4 and 24.6 ± 1.9%) and efferent (19.2 ± 2.9 and 19.1 ± 4.8%) arterioles. Adding diltiazem did not significantly augment the dilation of afferent arterioles elicited by pimozide and mibefradil, and adding pimozide after diltiazem likewise did not elicit further vasodilation. Diltiazem blocked the depolarization-induced afferent arteriolar constriction elicited by 55 mM KCl; however, the constrictor response to KCl remained intact during treatment with 10 μM pimozide. Pimozide also prevented the afferent arterioles from exhibiting autoregulatory-mediated constrictor responses to increases in perfusion pressure. We conclude that T-type channel blockers dilate efferent arterioles as well as afferent arterioles and diminish afferent arteriolar autoregulatory responses to changes in perfusion pressure. To the extent that these agents exert their effects primarily on T-type Ca2+ channels in our experimental setting, these results indicate that T-type channels are functionally expressed in juxtamedullary afferent and efferent arterioles and may act cooperatively with L-type channels to regulate afferent arteriolar resistance. Because L-type channels are not functionally expressed in efferent arterioles, T-type channels may be particularly significant in the regulation of efferent arteriolar function.

Angiotensin II effects on microvascular diameters of in vitro blood-perfused juxtamedullary nephrons

1986 ◽  
Vol 251 (4) ◽  
pp. F610-F618 ◽  
Author(s):  
P. K. Carmines ◽  
T. K. Morrison ◽  
L. G. Navar
Keyword(s):  
Angiotensin Ii ◽  
Constant Pressure ◽  
Ang Ii ◽  
Experimental Conditions ◽  
Vasoactive Hormones ◽  
Juxtamedullary Nephron ◽  
Single Nephron ◽  
Afferent Arterioles ◽  
Dose Dependent

The purpose of this study was to determine the specific renal microvascular segments that are functionally responsive to angiotensin II (ANG II) and other vasoactive hormones. Experiments were performed on juxtamedullary tissue from captopril-treated rats during perfusion with blood at a constant pressure of 110 mmHg. Epifluorescence videomicroscopy was utilized to measure diameters of arcuate and interlobular arteries (ART), mid- (MA) and late- (LA) afferent arterioles, and efferent arterioles (EA). Norepinephrine (700 nM) significantly decreased, and sodium nitroprusside (380 nM) increased, inside diameters of all segments. Topical application of ANG II (0.01 to 1 nM) induced significant reductions in diameters of all vessel segments: ART, 17.5 +/- 2.0%; MA, 19.6 +/- 2.5%; LA, 13.5 +/- 1.5%; and EA, 16.9 +/- 2.7%. The preglomerular response to ANG II was blocked by saralasin (10 microM) and, in most cases, was dose dependent; however, an initial hypersensitivity to low ANG II doses (30% decrease in diameter) was exhibited by 38% of the preglomerular vessels studied. Under these experimental conditions, single-nephron glomerular filtration rate decreased significantly in response to 0.01 nM ANG II exposure. These observations demonstrate that physiological concentrations of ANG II can elicit receptor-dependent and reversible vasoconstriction of the juxtamedullary nephron microvasculature at both pre- and postglomerular sites.

Direct evaluation of the microvascular actions of ANP in juxtamedullary nephrons

1988 ◽  
Vol 254 (3) ◽  
pp. F440-F444 ◽  
Author(s):  
P. J. Veldkamp ◽  
P. K. Carmines ◽  
E. W. Inscho ◽  
L. G. Navar
Keyword(s):  
Angiotensin Ii ◽  
Topical Administration ◽  
Normal Kidney ◽  
Arterial Diameter ◽  
Direct Evaluation ◽  
Juxtamedullary Nephron ◽  
Afferent Arterioles ◽  
Renal Vascular ◽  
Arteriolar Diameter

The renal vascular actions of atrial natriuretic peptide (ANP) remain incompletely understood. The purpose of this study is to evaluate the effects of ANP on microvascular structures of the normal kidney. The in vitro blood-perfused juxtamedullary nephron technique was utilized to allow visualization of arcuate arteries and afferent and efferent arterioles. Donor rats were pretreated with captopril to eliminate possible interactions between angiotensin II and atriopeptin III (AP III). The effects of topical administration of 3 nM AP III were determined by videometric analysis of vessel inside diameters. Under control conditions, arcuate arterial diameter averaged 83 +/- 14 microns (n = 7), afferent arteriolar diameter was 20 +/- 4 microns (n = 7), and efferent arteriolar diameter was 16 +/- 2 microns (n = 7). During superfusion with AP III, arcuate arteries and afferent arterioles dilated 73 +/- 9 and 23 +/- 5%, respectively. Both returned to their control values when AP III was removed from the superfusate. Further experiments on arcuate arteries (n = 5) revealed that 0.3 nM AP III also vasodilated these vessels (26 +/- 9%); however, no significant effect was elicited by 0.03 nM AP III. In contrast to the vasodilator influence of AP III on preglomerular vessels, efferent arteriolar diameter was not altered by AP III exposure. These observations reveal that AP III can induce selective preglomerular vasodilation involving arcuate arteries as well as afferent arterioles, while efferent arteriolar diameter is not perceptibly influenced.

Effects of ATP on pre- and postglomerular juxtamedullary microvasculature

1992 ◽  
Vol 263 (5) ◽  
pp. F886-F893 ◽  
Author(s):  
E. W. Inscho ◽  
K. Ohishi ◽  
L. G. Navar
Keyword(s):  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Renal Perfusion Pressure ◽  
Organ Systems ◽  
Smooth Muscle Function ◽  
Juxtamedullary Nephron ◽  
Afferent Arterioles ◽  
The Right ◽  
Dose Dependent

Based on evidence that extracellular ATP can influence vascular smooth muscle function in other organ systems, experiments were conducted to characterize the responsiveness of rat juxtamedullary microvascular segments to ATP. Experiments were performed using the in vitro blood-perfused juxtamedullary nephron preparation combined with video microscopy. Pentobarbital-anesthetized rats were pretreated with enalaprilat (2 mg iv) for 30 min before the right kidney was isolated and prepared for study. Renal perfusion pressure was set at 110 mmHg and held constant. Under control conditions, afferent and efferent arteriolar diameters averaged 19.9 +/- 1.4 (n = 19) and 21.6 +/- 1.2 microns (n = 10), respectively. Superfusion with 1, 10, and 100 microM ATP solutions induced sustained dose-dependent afferent vasoconstriction of 8.3 +/- 1.4, 12.8 +/- 1.7, and 12.1 +/- 2.1%, respectively (P < 0.01). Afferent vasoconstrictor responses to ATP were also observed during adenosine receptor blockade. In contrast, efferent arterioles were unresponsive to ATP stimulation even at concentrations as high as 100 microM (P > 0.05). Arcuate and interlobular arterial diameters averaged 82.0 +/- 15.7 (n = 5) and 43.4 +/- 4.5 microns (n = 6), respectively, during control conditions and responded to ATP treatment with a transient vasoconstriction followed by a gradual return to control diameter. Interlobular arteries exhibited a sustained constriction only at the 100 microM concentration (P < 0.05). These data demonstrate that afferent arterioles are more responsive to ATP treatment than other renal microvascular segments and suggest the presence of ATP-sensitive P2x purinoceptors on pre- but not postglomerular juxtamedullary microvascular elements.

Direct assessment of renal microvascular responses to P2-purinoceptor agonists

1998 ◽  
Vol 274 (4) ◽  
pp. F718-F727 ◽  
Author(s):  
Edward W. Inscho ◽  
Anthony K. Cook ◽  
Vy Mui ◽  
Jason Miller
Keyword(s):  
Vessel Diameter ◽  
Renal Perfusion ◽  
Receptor Subtypes ◽  
Selective Agonist ◽  
Juxtamedullary Nephron ◽  
Afferent Arterioles ◽  
Arcuate Artery ◽  
Arteriolar Diameter

Studies were performed to determine the responsiveness of rat juxtamedullary afferent arterioles to receptor-selective P2-purinoceptor agonists. Experiments were performed in vitro using the blood perfused juxtamedullary nephron technique, combined with videomicroscopy. Renal perfusion pressure was set at 110 mmHg and held constant. Basal afferent arteriolar diameter averaged 22.0 ± 0.6 μm ( n = 69). Stimulation with 0.1, 1.0, 10, and 100 μM ATP ( n = 10) elicited a concentration-dependent vasoconstriction averaging 8 ± 2, 17 ± 2, 21 ± 4, and 23 ± 5%, respectively. A nearly identical afferent arteriolar vasoconstriction was observed in response to the P2X-selective agonist β,γ-methylene ATP ( n = 10); however, another P2X agonist, α,β-methylene ATP, evoked marked receptor desensitization ( n = 10). Vessel diameter decreased by ∼7 ± 2, 16 ± 2, 23 ± 3, and 22 ± 3%, respectively, over the same concentration range. The P2Y-selective agonist, 2-methylthio-ATP, evoked only a modest vasoconstriction, whereas UTP and adenosine 5′- O-(3-thiotriphosphate) (ATPγS) reduced afferent diameter markedly at concentrations >1.0 μM. Afferent arteriolar diameter decreased by 5 ± 4, 31 ± 8, and 72 ± 8% during UTP administration ( n = 7) at concentrations of 1.0, 10, and 100 μM, respectively. Similarly, ATPγS ( n = 6) decreased afferent diameter by 16 ± 2, 58 ± 8, and 98 ± 3%, respectively, over the same concentration range. Nitric oxide synthesis inhibition with N ω-nitro-l-arginine did not significantly alter the afferent arteriolar response to ATP but did potentiate ATP-mediated arcuate artery vasoconstriction. The following data suggest the presence of multiple P2 receptors on juxtamedullary afferent arterioles and are consistent with classification of those receptors as members of the P2X- and P2Y2 (P2U)-receptor subtypes.

scholarly journals Human munc13 Is a Diacylglycerol Receptor that Induces Apoptosis and May Contribute to Renal Cell Injury in Hyperglycemia

1999 ◽  
Vol 10 (5) ◽  
pp. 1609-1619 ◽  
Author(s):  
Yong Song ◽  
Menachem Ailenberg ◽  
Mel Silverman
Keyword(s):  
Phorbol Ester ◽  
Renal Cell ◽  
Cell Injury ◽  
Rat Kidney ◽  
Diabetic Rat ◽  
Opossum Kidney ◽  
Opossum Kidney Cells ◽  
Renal Cell Line ◽  
Diabetic Rat Model

We have previously shown that human munc13 (hmunc13) is up-regulated by hyperglycemia under in vitro conditions in human mesangial cell cultures. The purpose of the present study was to determine the cellular function of hmunc13. To do this, we have investigated the subcellular localization of hmunc13 in a transiently transfected renal cell line, opossum kidney cells. We have found that hmunc13 is a cytoplasmic protein and is translocated to the Golgi apparatus after phorbol ester stimulation. In addition, cells transfected with hmunc13 demonstrate apoptosis after treatment with phorbol ester, but cells transfected with an hmunc13 deletion mutant in which the diacylglycerol (C1) binding domain is absent exhibit no change in intracellular distribution and no induction of apoptosis in the presence of phorbol ester stimulation. We conclude that both the diacylglycerol-induced translocation and the apoptosis represent functional activity of hmunc13. We have also demonstrated that munc13-1 and munc13-2 are localized mainly to cortical epithelial cells in rat kidney and both are overexpressed under conditions of hyperglycemia in a streptozotocin-treated diabetic rat model. Taken together, our data suggest that hmunc13 serves as a diacylglycerol-activated, PKC-independent signaling pathway capable of inducing apoptosis and that this pathway may contribute to the renal cell complications of hyperglycemia.

Praziquantel and the benzodiazepine Ro 11-3128 do not compete for the same binding sites in schistosomes

Parasitology ◽  
2007 ◽  
Vol 135 (1) ◽  
pp. 47-54 ◽  
Author(s):  
L. PICA-MATTOCCIA ◽  
A. RUPPEL ◽  
C. M. XIA ◽  
D. CIOLI
Keyword(s):  
Calcium Channel ◽  
Binding Sites ◽  
Calcium Influx ◽  
Cytochalasin D ◽  
The Other ◽  
Channel Blockers ◽  
Spastic Paralysis ◽  
Receptor Sites

SUMMARYThe benzodiazepine Ro 11-3128 (methyl-clonazepam) presents several similarities with praziquantel with regard to its anti-schistosomal mode of action, since both drugs cause spastic paralysis, calcium influx and tegumental disruption in the parasites. In order to know whether the two compounds share the same binding sites in the schistosomes, we performed in vivo and in vitro competition experiments. We took advantage of the fact that Ro 11-3128 is active against immature Schistosoma mansoni (whereas praziquantel is inactive), and praziquantel is active against S. japonicum (which is insensitive to Ro 11-3128). An excess of praziquantel did not inhibit the activity of Ro 11-3128 against immature S. mansoni and an excess of Ro 11-3128 did not inhibit the activity of praziquantel against S. japonicum, suggesting that the schistosome binding sites of the two drugs are different. On the other hand, cytochalasin D, an agent known to perturb – among other things – calcium channel function, was capable of inhibiting the schistosomicidal activity of both praziquantel and Ro 11-3128, thus adding another element of similarity between the two anti-schistosomal agents. A similar, albeit partial, inhibition of the schistosomicidal activity of the two drugs was exerted by some of the classical calcium channel blockers. Taken together, these results suggest that praziquantel and Ro 11-3128, although binding to different schistosome receptor sites, may use the same basic anti-schistosomal effector mechanisms.

Excitation of cutaneous sensory nerve endings in the rat by 4-aminopyridine and tetraethylammonium

1992 ◽  
Vol 67 (1) ◽  
pp. 125-131 ◽  
Author(s):  
C. Kirchhoff ◽  
J. D. Leah ◽  
S. Jung ◽  
P. W. Reeh
Keyword(s):  
Potassium Channel ◽  
Sensory Nerve ◽  
Low Frequency ◽  
Threshold Concentration ◽  
Nerve Endings ◽  
Channel Blockers ◽  
C Fibers ◽  
Sensory Nerve Endings ◽  
Potassium Channel Blockers

1. The effects of the potassium channel blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on cutaneous sensory nerve endings have been investigated with the use of an in vitro skin-nerve preparation from the rat. 2. Direct application of these compounds to the nerve endings, but not to the axons, induced continuous discharges in most A beta, A delta, and C fibers. There was no relationship between the fibers' responsiveness or the threshold concentration required to induce discharges and either the conduction velocity or sensory properties of the fibers. 3. The rate of induced discharges increased linearly with increasing concentrations of 4-AP. At threshold concentrations of 10(-6)-10(-5) M, low-frequency, irregular discharges developed; but at the highest concentration of 10(-3) M, a characteristic doublet or bursting discharges usually emerged. 4. During and after the induced discharges there did not appear to be an alteration in the sensitivity of the sensory nerve endings to mechanical or thermal stimuli. 5. It is concluded that the induced activity arises from an action of these potassium channel blockers at or near the action potential generator region at the nerve endings.

Inhibitory effects of potassium channel blockers on tetramethylpyrazine-induced relaxation of rat aortic strip in vitro

Life Sciences ◽  
2002 ◽  
Vol 71 (11) ◽  
pp. 1321-1330 ◽  
Author(s):  
Chin-Chuan Tsai ◽  
Tung-Yuan Lai ◽  
Wei-Chan Huang ◽  
I-Min Liu ◽  
Juei-Tang Cheng
Keyword(s):  
Potassium Channel ◽  
Channel Blockers ◽  
Inhibitory Effects ◽  
Aortic Strip ◽  
Potassium Channel Blockers

Redundant signaling mechanisms contribute to the vasodilatory response of the afferent arteriole to proteinase-activated receptor-2

2005 ◽  
Vol 288 (1) ◽  
pp. F65-F75 ◽  
Author(s):  
Xuemei Wang ◽  
Morley D. Hollenberg ◽  
Rodger Loutzenhiser
Keyword(s):  
Rat Kidney ◽  
Combined Treatment ◽  
Afferent Arteriole ◽  
Vasodilatory Response ◽  
Signaling Mechanisms ◽  
Afferent Arterioles ◽  
Arteriolar Vasodilation ◽  
Dependent Mechanism ◽  
Stimulation Of

We previously demonstrated that stimulation of proteinase-activated receptor-2 (PAR-2) by SLIGRL-NH2 elicits afferent arteriolar vasodilation, in part, by elaborating nitric oxide (NO), suggesting an endothelium-dependent mechanism (Trottier G, Hollenberg M, Wang X, Gui Y, Loutzenhiser K, and Loutzenhiser R. Am J Physiol Renal Physiol 282: F891–F897, 2002). In the present study, we characterized the NO-independent component of this response, using the in vitro perfused hydronephrotic rat kidney. SLIGRL-NH2 (10 μmol/l) dilated afferent arterioles preconstricted with ANG II, and the initial transient component of this response was resistant to NO synthase (NOS) and cyclooxygenase inhibition. This NO-independent response was not prevented by treatment with 10 nmol/l charybdotoxin and 1 μmol/l apamin, a manipulation that prevents the endothelium-derived hyperpolarizing factor (EDHF)-like response of the afferent arteriole to acetylcholine, nor was it blocked by the addition of 1 mmol/l tetraethylammonium (TEA) or 50 μmol/l 17-octadecynoic acid, treatments that block the EDHF-like response to bradykinin. To determine whether the PAR-2 response additionally involves the electrogenic Na+-K+-ATPase, responses were evaluated in the presence of 3 mmol/l ouabain. In this setting, SLIGRL-NH2 induced a biphasic dilation in control and a transient response after NOS inhibition. The latter was not prevented by charybdotoxin plus apamin or by TEA alone but was abolished by combined treatment with charybdotoxin, apamin, and TEA. This treatment did not prevent the NO-dependent dilation evoked in the absence of NOS inhibition. Our findings indicate a remarkable redundancy in the signaling cascade mediating PAR-2 -induced afferent arteriolar vasodilation, suggesting an importance in settings such as inflamation or ischemia, in which vascular mechanisms might be impaired and the PAR system is thought to be activated.

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