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

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.

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Direct evaluation of the microvascular actions of ANP in juxtamedullary nephrons

AJP Renal Physiology ◽

10.1152/ajprenal.1988.254.3.f440 ◽

1988 ◽

Vol 254 (3) ◽

pp. F440-F444 ◽

Cited By ~ 3

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.

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Effects of ATP on pre- and postglomerular juxtamedullary microvasculature

AJP Renal Physiology ◽

10.1152/ajprenal.1992.263.5.f886 ◽

1992 ◽

Vol 263 (5) ◽

pp. F886-F893 ◽

Cited By ~ 34

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.

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High intraluminal pressure via H2O2 upregulates arteriolar constrictions to angiotensin II by increasing the functional availability of AT1 receptors

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00205.2008 ◽

2008 ◽

Vol 295 (2) ◽

pp. H835-H841 ◽

Cited By ~ 22

Author(s):

Zsolt Bagi ◽

Nora Erdei ◽

Akos Koller

Keyword(s):

High Pressure ◽

Angiotensin Ii ◽

Renin Angiotensin System ◽

Intraluminal Pressure ◽

Ang Ii ◽

At1 Receptors ◽

Angiotensin System ◽

Dose Dependent

Previously, we found that high intraluminal pressure leads to production of reactive oxygen species (ROS) and also upregulates several components of the renin-angiotensin system in the wall of small arteries. We hypothesized that acute exposure of arterioles to high intraluminal pressure in vitro via increasing ROS production enhances the functional availability of type 1 angiotensin II (Ang II) receptors (AT1 receptors), resulting in sustained constrictions. In arterioles (∼180 μm) isolated from rat skeletal muscle, Ang II elicited dose-dependent constrictions, which decreased significantly by the second application [maximum (max.): from 59% ± 4% to 26% ± 5% at 10−8 M; P < 0.05] in the presence of 80 mmHg of intraluminal pressure. In contrast, if the arterioles were exposed to high intraluminal pressure (160 mmHg for 30 min), Ang II-induced constrictions remained substantial on the second application (max.: 51% ± 3% at 10−8 M). In the presence of Tiron and polyethylene glycol (PEG)-catalase, known to reduce the level of superoxide anion and hydrogen peroxide (H2O2), second applications of Ang II evoked similarly reduced constrictions, even after high-pressure exposure (29% ± 4% at 10−8 M). Furthermore, when arterioles were exposed to H2O2 (for 30 min, 10−7 M, at normal 80 mmHg pressure), Ang II-induced constrictions remained substantial on second applications (59% ± 5% at 10−8 M). These findings suggest that high pressure, likely via inducing H2O2 production, increases the functional availability of AT1 receptors and thus enhances Ang II-induced arteriolar constrictions. We propose that in hypertension–regardless of etiology–high intraluminal pressure, via oxidative stress, enhances the functional availability of AT1 receptors augmenting Ang II-induced constrictions.

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Segmental effects of norepinephrine and angiotensin II on isolated renal microvessels

AJP Renal Physiology ◽

10.1152/ajprenal.1983.244.5.f526 ◽

1983 ◽

Vol 244 (5) ◽

pp. F526-F534 ◽

Cited By ~ 24

Author(s):

R. M. Edwards

Keyword(s):

Angiotensin Ii ◽

Contractile Response ◽

Intraluminal Pressure ◽

Lumen Diameter ◽

Rabbit Kidney ◽

Ang Ii ◽

Efferent Arteriole ◽

Afferent Arterioles ◽

Dose Dependent Decrease ◽

Dose Dependent

Interlobular arteries and superficial afferent and efferent arterioles were isolated from rabbit kidney, and the effects of intraluminal pressure, norepinephrine (NE), and angiotensin II (ANG II) on lumen diameter were examined. A single microvessel was dissected and one end was cannulated. The other end of the vessel was occluded and lumen diameter was measured at fixed intraluminal pressures. With step increases in intraluminal pressure over the range of 70-180 mmHg, lumen diameters of the interlobular arteries and afferent arterioles remained constant or decreased by up to 11%. In contrast, lumen diameters of efferent arterioles continued to increase as intraluminal pressure was elevated. In all three vessels NE (10(-9) to 10(-5) M) caused a dose-dependent decrease in lumen diameter. However, only the efferent arteriole responded to ANG II (10(-12) to 10(-8) M). The contractile response of the efferent arteriole to NE or ANG II was localized to the first 50-75 micrometers of the vessel as it emerged from the glomerulus. This finding suggests that smooth muscle cells are located only in this portion of the efferent arteriole. It is concluded that at least part of the autoregulation of renal blood flow can be explained by a myogenic mechanism in preglomerular vessels and that ANG II acts primarily on postglomerular segments of the rabbit renal microcirculation.

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Disparate effects of Ca channel blockade on afferent and efferent arteriolar responses to ANG II

AJP Renal Physiology ◽

10.1152/ajprenal.1989.256.6.f1015 ◽

1989 ◽

Vol 256 (6) ◽

pp. F1015-F1020 ◽

Cited By ~ 58

Author(s):

P. K. Carmines ◽

L. G. Navar

Keyword(s):

Calcium Antagonist ◽

Angiotensin Ii ◽

Calcium Channel Blockers ◽

Channel Blockers ◽

Ca Channel ◽

Ang Ii ◽

Channel Blockade ◽

Afferent Arterioles ◽

Organic Calcium Antagonists

Previous reports have suggested that organic calcium antagonists only partially inhibit the renal hemodynamic actions of angiotensin II (ANG II). This study tested the hypothesis that the calcium antagonist-sensitive component of ANG II-induced vasoconstriction is localized at a preglomerular site. Videomicroscopic measurements of vascular dimension were performed on in vitro blood-perfused juxtamedullary nephrons from captopril-treated rats. Under control conditions, afferent and efferent arteriolar diameters averaged 23.0 +/- 1.6 and 21.2 +/- 2.2 microns, respectively. Topical application of 0.1 nM ANG II decreased the diameters of afferent (-17 +/- 2%) and efferent (-15 +/- 3%) arterioles. Both 50 microM verapamil and 10 microM diltiazem dilated afferent arterioles. Verapamil also elicited a modest efferent vasodilation. In the presence of either verapamil or diltiazem, the effect of ANG II to decrease efferent diameter was sustained (-15 +/- 4%); however, the effect of ANG II on afferent diameter was abolished (-1 +/- 1%). These observations document differential influences of calcium channel blockers on ANG II-mediated vasoconstriction and suggest that the pre- and postglomerular vasoconstrictor actions of ANG II may occur through different calcium entry or mobilization mechanisms.

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Angiotensin II relaxation of rainbow trout vessels in vitro

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.266.6.r1856 ◽

1994 ◽

Vol 266 (6) ◽

pp. R1856-R1860 ◽

Cited By ~ 8

Author(s):

D. J. Conklin ◽

K. R. Olson

Keyword(s):

Angiotensin Ii ◽

Effective Concentration ◽

Partial Recovery ◽

Ang Ii ◽

Systemic Arch ◽

Ventral Aorta ◽

Dose Dependent ◽

Large Vessels ◽

Predominant Effect

The effects of salmonid angiotensin II ([Asn1,Val5]ANG II) were examined in isolated trout arteries [celiacomesenteric (CMA), coronary (COA), 3rd or 4th gill arch epibranchial (EBA), ventral aorta (VA)] and veins [anterior cardinal (ACV) and ductus Cuvier strips (DOC)]. ANG II (10(-10)-10(-6) M) produced modest (< 50% other agonists) transient contractions in otherwise unstimulated COA but was a poor agonist in other vessels. In precontracted vessels, ANG II responses were triphasic; transient contraction (P1), relaxation (P2), and partial recovery (P3) and vessel specific. P1 was similar to uncontracted vessels. With 10(-6) MANG II, %P2 was: EBA, 60.3 +/- 8.3% (n = 22); CMA, 48.8 +/- 8.8% (n = 4); ACV, 38.8 +/- 5.3% (n = 29); VA, 29.4 +/- 4.9% (n = 8); DOC, 25.5 +/- 2.4% (n = 14); COA, 13.2 +/- 6.7% (n = 4). P2 in EBA and ACV was dose dependent [EBA vs. ACV: mean effective concentration (EC50) = 3.6 x 10(-9) +/- 8.1 x 10(-10) M, n = 7 vs. 6.2 x 10(-8) +/- 2.3 x 10(-8) M, n = 8, respectively; P < or = 0.05] and inhibited by indomethacin but unaffected by propranolol, NG-monomethyl-L-arginine, saralasin, PD-123177, or DuP-753. Removal of EBA endothelium also inhibited relaxation. By comparison, ANG II did not relax bullfrog arteries (dorsal aorta, systemic arch, CMA) or femoral veins. These results show that, in large vessels of trout, the predominant effect of ANG II is an endothelium-dependent, prostanoid-mediated relaxation that is unaffected by classical ANG II-receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

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Differential regulation of angiotensin II and losartan binding sites in glomeruli and mesangial cells

AJP Renal Physiology ◽

10.1152/ajprenal.1994.266.3.f384 ◽

1994 ◽

Vol 266 (3) ◽

pp. F384-F393 ◽

Cited By ~ 5

Author(s):

D. Chansel ◽

T. Bizet ◽

S. Vandermeersch ◽

P. Pham ◽

B. Levy ◽

...

Keyword(s):

Angiotensin Ii ◽

Binding Sites ◽

Mesangial Cells ◽

Present Report ◽

Mrna Levels ◽

Ang Ii ◽

Experimental Conditions ◽

Human Mesangial Cells

The aim of the present report was to examine the effect of several agents on angiotensin II (ANG II) and losartan receptors using 125I-[Sar1,Ala8]ANG II and [3H]losartan as radiolabeled ligand, respectively. ANG II receptors were downregulated in glomeruli from rats infused with ANG II during 3 wk or rats receiving losartan orally during 1 wk. The number of sites (Bmax) was reduced, but the dissociation constant (Kd) value was unchanged. Losartan receptors were downregulated in glomeruli from rats receiving losartan, but remained unchanged in glomeruli from rats infused with ANG II. Since in vivo administration of losartan results in increase of plasma ANG II and formation of metabolites, in vitro studies using human mesangial cells were performed to better analyze the present findings. Treatment of mesangial cells during 4 days by ANG II, losartan, or its metabolite, EXP-3174, also produced downregulation of 125I-[Sar1,Ala8]ANG II binding sites with a decreased Bmax and unchanged Kd value. Only treatment of mesangial cells by ANG II or EXP-3174 produced downregulation of [3H]losartan binding sites. In contrast, exposure of these cells to losartan resulted in upregulation of [3H]losartan binding sites. Under all conditions, only Bmax was modified. Whereas internalization of [3H]losartan in mesangial cells was negligible under all experimental conditions, there was an increase of the percentage of internalized 125I-[Sar1,Ala8]ANG II after exposure of the cells to ANG II or AT1 antagonists. No change was observed in mesangial cell AT1 receptor mRNA levels. This study demonstrates that 1) AT1 mRNA is expressed in human mesangial cells; 2) the characteristics of 125I-[Sar1,Ala8]ANG II and [3H]losartan binding sites in rat glomeruli and human mesangial cells are different, with Kd and Bmax values greater in both preparations when [3H]losartan was utilized; 3) both types of binding sites obey different regulations, and the effects of losartan in vivo are due in part to the associated increase in plasma ANG II levels and the transformation of the drug into its metabolite, EXP-3174; 4) downregulation of AT1 receptors does not depend on changes in mRNA expression but is associated with increased relative internalization.

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Prostaglandin influences on afferent arteriolar responses to vasoconstrictor agonists

AJP Renal Physiology ◽

10.1152/ajprenal.1990.259.1.f157 ◽

1990 ◽

Vol 259 (1) ◽

pp. F157-F163 ◽

Cited By ~ 15

Author(s):

E. W. Inscho ◽

P. K. Carmines ◽

L. G. Navar

Keyword(s):

Topical Administration ◽

Bathing Solution ◽

Ang Ii ◽

Experimental Setting ◽

Vasoconstrictor Response ◽

Juxtamedullary Nephron ◽

Afferent Arterioles ◽

Renal Microvasculature ◽

Arteriolar Diameter

The present study was designed to evaluate, at the microvascular level, the ability of prostaglandins E2 (PGE2) and I2 (PGI2) to counteract the afferent vasoconstrictor effects of angiotensin II (ANG II) and norepinephrine (NE). The renal microvasculature of rats pretreated with captopril and indomethacin was studied directly by use of the in vitro blood-perfused juxtamedullary nephron technique combined with videomicroscopy. Afferent arterioles averaged 22.7 +/- 0.6 microns ID (n = 59) under control conditions. Topical administration of PGE2 revealed a concentration-dependent afferent vasoconstriction, whereas PGI2 (10(-7) to 10(-5) M) failed to significantly alter afferent arteriolar diameter. Afferent arterioles constricted during exposure to either 10(-9) M ANG II (-15 +/- 3%, n = 13) or 10(-7) M NE (-19 +/- 3%, n = 13). Addition of PGE2 (10(-6) M) to the bathing solution enhanced the vasoconstrictor influences of ANG II and NE by an additional 18 +/- 6 and 13 +/- 4%, respectively. In contrast, while 10(-6) M PGI2 had no effect on ANG II-induced afferent vasoconstriction, it did produce a 30% attenuation of NE-induced constriction. Furthermore, pretreatment of the tissue with 10(-6) M PGI2 prevented development of NE-induced afferent vasoconstriction. Thus, although local tissue prostanoid concentrations are unknown, it appears that low micromolar concentrations of PGE2 elicit an afferent arteriolar constriction that can accentuate the vascular actions of ANG II and NE on rat juxtamedullary afferent arterioles. In contrast, PGI2 can counteract the vasoconstrictor response to NE, but not ANG II, in this experimental setting.

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

AJP Renal Physiology ◽

10.1152/ajprenal.00563.2007 ◽

2008 ◽

Vol 295 (1) ◽

pp. F171-F178 ◽

Cited By ~ 23

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.

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