Papillary Blood Flow Research Articles

Analysis of Blood Flow in the Macula and Optic Nerve Head in Healthy Young Volunteers Using Laser Speckle Flowgraphy.

To assess optic nerve head (ONH) and macular blood flow in young healthy volunteers using laser speckle flowgraphy (LSFG). This is a prospective single-center study conducted at the Department of Ophthalmology, University Hospital Zurich from May to November 2021. Young, healthy men aged ≥ 18 years without ocular or systemic diseases were included. A corrected visual acuity (VA) of 0.0 logMAR or better in both eyes and an intraocular pressure (IOP) of 21 mmHg or lower were required for inclusion. Subjects exceeding a spherical equivalent (SE) of ± 6 diopters (dpt) were excluded. Blood flow in the macula and the ONH was recorded using the Nidek LSFG RetFlow device (Nidek Company, Ltd., Hirioshi-cho, Japan). Laser power was set to 0.5 Millivolts (mV). Mean blur rate (MBR) was recorded as a parameter for blood flow. MBR is a calculated parameter that represents relative blood flow velocity correlated with the real anatomical blood flow rate. Colored heat maps of the recorded retinal area were generated automatically by the RetFlow device. Final analyses included 83 eyes of 43 male volunteers. Mean age was 21.9 years (SD ± 1.5, range: 20 to 29). Mean corrected VA was - 0.1 logMAR (SD ± 0.05, range: - 0.2 to 0.0), mean IOP was 15.4 mmHg (SD ± 2.5, range: 8.5 to 18.5), and mean SE was - 0.3 dpt (SD ± 1.2, range: - 5.0 to 1.2). Mean ONH MBR was 37.44 (SD ± 7.9, range: 22.5 to 53.5) and mean macular MBR was 27.8 (SD ± 9.7, range: 6.4 to 57.7). Pearson's Test showed a strong correlation between macular and papillary blood flow (p < 0.05, coefficient: 0.647). This study provides both ONH and macular blood flow data in a healthy young male population, showing a strong correlation between ONH and macular blood flow in the examined eyes. Further investigations are required to assess the validity of MBR as a parameter for the combined evaluation of retinal blood flow at the macula and ONH in healthy volunteers and patients with various diseases.

PD04-04 URETEROSCOPIC DOPPLER ULTRASONOGRAPHY: MAPPING RENAL BLOOD FLOW FROM THE INSIDE-OUT

INTRODUCTION AND OBJECTIVES:Detailed knowledge of forniceal and papillary blood flow would be helpful in determining the least vascular site for the placement of a nephrostomy track for percutaneou...

Application of optical coherence tomography angiography in assessment of posterior scleral reinforcement for pathologic myopia.

To investigate the effect of posterior scleral reinforcement (PSR) on circulation of pathologic myopia eyes with posterior staphyloma by optical coherence tomography angiography (OCTA). The study included 30 pathologic myopia eyes with posterior staphyloma which underwent PSR (PSR group) for 6 to 18mo ago, and 30 age and myopia matched eyes without PSR surgery as control group. Macular, choriocapillaris and radial peripapillary capillary (RPC) flow density were measured by OCTA, and the measurements were compared between groups. OCTA found no significant differences in macular flow density between PSR and control groups. For the superficial flow, whole enface flow density (WED), fovea density (FD), and parafoveal density (PD) were 46.55%±5.19% vs 47.29%±4.12% (P=0.542), 31.45%±6.35% vs 31.17%±4.48% (P=0.841), and 48.82%±5.66% vs 49.21%±4.15% (P=0.756) in PSR and control groups, respectively. For the deep flow, WED, FD, and PD were 52.07%±5.78% vs 53.95%±4.62% (P=0.168), 29.62%±6.55% vs 29.50%±6.38% (P=0.940), and 56.93%±6.17% vs 58.15%±5.13% (P=0.407) in PSR and control groups, respectively. The choriocapillary flow density was 61.18±3.25% in PSR group vs 60.88%±2.56% in control group (P=0.692). Also, OCTA found no significant differences in RPCs flow density between PSR and control groups. The optic disc WED, inside disc flow density and peripapillary flow density were 48.47%±4.77% vs 48.11%±4.57% (P=0.813), 45.47%±11.44% vs 46.68%±9.02% (P=0.709), 54.32%±5.29% vs 52.47%±6.62% (P=0.349) in PSR and control groups, respectively. OCTA provides a non-invasive and quantitative approach for monitoring macular and papillary blood flow in pathologic myopia. PSR can not improve but may maintain the circulation of pathologic myopia eyes with posterior staphyloma.

Nitric oxide, prostaglandins and angiotensin II in the regulation of renal medullary blood flow during volume expansion.

Regulation of medullary blood flow (MBF) is essential in maintaining renal function and blood pressure. However, it is unknown whether outer MBF (OMBF) and papillary blood flow (PBF) are regulated independently when extracellular volume (ECV) is enhanced. The aim of this study was to determine whether OMBF and PBF are differently regulated and whether there is an interaction between nitric oxide (NO), prostaglandins (PGs) and angiotensin II (Ang II) in regulating OMBF and PBF when ECV is enhanced. To achieve these goals, OMBF and PBF were measured by laser-Doppler in volume-expanded rats treated with a cyclooxygenase inhibitor (meclofenamate, 3mg/kg) and/or a NO synthesis inhibitor (L-nitro-arginine methyl ester (L-NAME), 3μg/kg/min) and/or Ang II (10ng/kg/min). OMBF was unchanged by NO or PGs synthesis inhibition but decreased by 36% (P < 0.05) when L-NAME and meclofenamate were infused simultaneously. PBF was similarly reduced by L-NAME (12%), meclofenamate (17%) or L-NAME + meclofenamate (19%). Ang II did not modify OMBF, but it led to a similar decrease (P < 0.05) in OMBF when it was administered to rats with reduced NO (32%), PGs (36%) or NO and PGs (37%) synthesis. In contrast, the fall in PBF induced by Ang II (12%) was enhanced (P < 0.05) by the simultaneous PGs (30%) or PGs and NO (31%) synthesis inhibition but not in L-NAME-treated rats (20%). This study presents novel findings suggesting that blood flows to the outer medulla and renal papilla are differently regulated and showing that there is a complex interaction between NO, PGs and Ang II in regulating OMBF and PBF when ECV is enhanced.

Effect of topical carteolol on visual function in normal-tension glaucoma

The effects of carteolol hydrochloride on visual function in normal-tension glaucoma (NTG) were investigated. 22eyes of NTG patients were divided into two groups, i.e., (1) a group receiving topical application of 2% carteolol hydrochloride b.i.d. and 2 an unmedicated group. During a 18 month period, intraocular pressure and visual field (measured by Humphrey automated perimetry) were measured every 3 months, and the measurements obtained in the two groups were compared. Analysis of the results revealed a considerable reduction in intraocular pressure in the carteolol group as compared with the control group. The progression of mean deviation tended to be less in the carteolol group, but the intergroup difference in this respect was not statistically significant. However, increase in corrected pattern standard deviation was clearly less pronounced in the carteolol group than in the control group. These results supported the conclusion that carteolol is effective in inhibiting deterioration of the local visual field. This is attributed to increased ocular perfusion due to diminished intraocular pressure, as well as an inhibitory effect upon vasoconstriction in the optic nerve head due to intrinsic sympathomimetic activity, preventing decrease in papillary blood flow and adverse effects upon ocular circulation.

Blockade of renal medullary bradykinin B2 receptors increases tubular sodium reabsorption in rats fed a normal-salt diet.

The present study was performed to test the hypothesis that under normal physiological conditions and/or during augmentation of kinin levels, intrarenal kinins act on medullary bradykinin B(2) (BKB(2)) receptors to acutely increase papillary blood flow (PBF) and therefore Na(+) excretion. We determined the effect of acute inner medullary interstitial (IMI) BKB(2) receptor blockade on renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied. Baseline renal hemodynamic and excretory function were determined during IMI infusion of 0.9% NaCl into the left kidney. The infusion was then either changed to HOE-140 (100 microg.kg(-1).h(-1), treated group) or maintained with 0.9% NaCl (time control group), and the parameters were again determined. In rats fed a normal-salt diet, HOE-140 infusion decreased left kidney Na(+) excretion (urinary Na(+) extraction rate) and fractional Na(+) excretion by 40 +/- 5% and 40 +/- 4%, respectively (P < 0.01), but did not alter glomerular filtration rate, inner medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet, HOE-140 infusion did not alter renal regional hemodynamics or excretory function. We conclude that in rats fed a normal-salt diet, kinins act tonically via medullary BKB(2) receptors to increase Na(+) excretion independent of changes in inner medullary blood flow.

Retinal colour duplex scanning during LASIK-ring suction with different keratomes

The purpose was to measure the blood flow velocity during the suction phase of LASIK. University Eye Hospital, Martin-Luther-University Halle-Wittenberg, Halle, Germany. Papillary blood flow velocity was measured by colour Doppler sonography. Suction rings of four different manufacturers were applied in 30 healthy volunteers without eye diseases all of normal blood and eye pressure. The velocity of the blood flow in the central retinal artery was measured before, during and after suction. When Hansatome (Bausch & Lomb) and M2 (Moria) rings were used, no blood flow velocity was detected during suction in 90% of all cases. These rings were compared to the SKBM standard suction ring (Alcon) and the Krumeich non-IOP ring, in which no blood was present in only 56.67% (p < 0.05) and 10% (p < 0.001) of cases respectively. Moria, Alcon and Krumeich Lasitome rings performed equally well during the recovery phase compared with the original values. An exception is the Hansatome ring (Bausch & Lomb), with lower velocities when evaluated after 30 minutes (p < 0.01). During the ring suction phase of LASIK, the rings tested reduce velocity differently.

Role of kinins in the control of renal papillary blood flow, pressure natriuresis, and arterial pressure.

The present study evaluated the effects of blocking kinins with the bradykinin B(2) receptor antagonist Hoe140 on the relationship between renal perfusion pressure, papillary blood flow (PBF), and sodium excretion. To determine the relevance of renal kinins in the long-term control of arterial pressure, the effect of a chronic intrarenal infusion of Hoe140 on arterial pressure and sodium balance was also studied. PBF was not autoregulated in volume-expanded rats, and the administration of Hoe140 reduced PBF (-30%) and improved PBF autoregulation. The kinin antagonist also decreased sodium excretion (-35%) and blunted pressure natriuresis with no whole-kidney renal hemodynamic changes. These effects may be mediated through nitric oxide (NO), because in rats pretreated with N(G)-nitro-L-arginine methyl ester, Hoe140 had no additional effects on PBF or pressure natriuresis. A role for NO in mediating the renal response to Hoe140 is also supported by the finding that Hoe140 reduced basal urinary NO(3)(-)/NO(2)(-) excretion (-33%), and it blunted the arterial pressure-induced increase in NO(3)(-)/NO(2)(-) excretion, which is compatible with the idea that the pressure-natriuresis response may be mediated through kinins and NO. The importance of kinins in long-term regulation of arterial pressure is demonstrated by the severe arterial hypertension (172+/-6 mm Hg) induced during the chronic intrarenal infusion of Hoe140 associated with sodium and volume retention. These data suggest that renal kinins and NO may be a part of the renal mechanism coupling changes in arterial pressure with modifications in PBF and sodium excretion, therefore contributing to the long-term control of arterial pressure.

Regional Renal Haemodynamics of Angiotensin II Infusion under Prostaglandin, Kinin or Converting Enzyme Inhibition in the Wistar Rat

Aims: Renal medullary blood flow is important in blood pressure regulation and is surprisingly unaffected by the vasoconstrictor action of angiotensin II (Ang II). This study tested if the effect of Ang II on the renal papillary circulation is modulated by bradykinins, prostaglandins or NO (NO). In anaesthetised Wistar rats, total renal blood flow (RBF) was measured, as was cortical (CBF) and papillary (PBF) blood flow, using the laser-Doppler technique, in responses to Ang II (30 ng kg-1 min-1) alone and after ACE inhibition (enalapril) or bradykinin/prostaglandin synthesis inhibition (ketoprofen, aprotinin). PBF was also measured after blockade of NO formation with or without pretreatment with an Ang II receptor antagonist (losartan). Major findings: (i) PBF did not change in response to Ang II infusion but MAP increased (+10%) and RBF and CBF decreased. (ii) Treatment with aprotinin and ketoprofen left MAP, RBF and CBF unchanged but decreased PBF. Ang II did not decrease PBF further but a significant increase in MAP was seen. (iii) Enalapril treatment left PBF unchanged but decreased MAP and increased RBF and CBF. When Ang II was infused PBF and MAP increased markedly. (iv) L-NAME reduced PBF independently of losartan treatment. Principal conclusion: Bradykinin and prostaglandins do not appear to cause the lack of renal papillary vasoconstriction to Ang II. However, the increase in PBF to Ang II seen after enalapril treatment suggests that enalapril treatment, possibly via its effects on kinin break-down and subsequent NO formation, might affect the sensitivity of renal papillary autoregulation. This may be an important aspect of the blood pressure lowering effect of ACE inhibitors.

Role of AT1 receptors in the renal papillary effects of acute and chronic nitric oxide inhibition.

Nitric oxide (NO) is a vasodilator substance controlling renal papillary blood flow (PBF) in the rat. In this study we have evaluated the role of AT1 angiotensin II receptors as modulators of the whole kidney and papillary vasoconstrictor effects induced by the acute or chronic inhibition of NO synthesis. Experiments have been performed in anesthetized, euvolemic Munich-Wistar rats prepared for the study of renal blood flow (RBF) and PBF. In normal rats, acute administration of the NO synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) increased mean arterial pressure (MAP) and decreased RBF and PBF. Either acute or chronic treatment with the AT1 receptor blocker losartan did not modify the decreases in RBF or PBF secondary to L-NAME. In animals made hypertensive by chronic inhibition of NO, basal MAP was higher, whereas RBF and PBF were lower than in the controls. In these animals, acute or chronic administration of losartan decreased MAP and increased both RBF and PBF significantly. These results indicate that, under normal conditions, the decreases in RBF or PBF induced by the acute inhibition of NO synthesis are not modulated by AT1-receptor stimulation. However, the arterial hypertension, renal vasoconstriction, and reduced PBF present in chronic NO-deficient hypertensive rats is partially due to the effects of angiotensin II, via stimulation of AT1-receptors.

Visual field defect and perfusion of the juxtapapillary retina and the neuroretinal rim area in primary open-angle glaucoma.

At this time little information is available about the relationship between glaucomatous visual field defects and impaired blood flow in the optic nerve head. The purpose of this study was to examine blood flow of the juxtapapillary retina and the rim area of the optic nerve head in primary open-angle glaucoma with a borderline visual defect. Juxtapapillary retinal and neuroretinal rim area blood flow was measured by scanning laser Doppler flowmetry (SLDF). The visual field was evaluated by static perimetry (Octopus-G1). The optic nerve head was assessed on 15 degrees color stereo photographs. We examined 116 eyes of 91 patients with POAG with controlled IOP and 66 eyes of 44 healthy individuals. The POAG group was divided into eyes with a mean defect lower than 2 dB (POAG group I) and in eyes with a mean defect equal to or greater than 2 dB (POAG group II). The mean age of POAG group I and POAG group II was 55 +/- 11 years and 57 +/- 10 years, respectively. The mean age of the control group was 45 +/- 15 years. The eyes of POAG group I had an average C/D ratio of 0.71 +/- 0.18 with an average mean defect of the visual field of 0.97 +/- 0.68 dB; the eyes of POAG group II had an average C/D ratio of 0.80 +/- 0.17 with an average mean defect of the visual field of 8.2 +/- 6.0 dB. The intraocular pressure on the day of measurement in POAG group I was 18.2 +/- 3.7 mmHg, in POAG group II 17.6 +/- 4.0 mmHg, and in the control group 15.1 +/- 2.5 mmHg. For statistical analysis, age-matched groups of 32 normal eyes of 32 subjects (mean age 52 +/- 10 years) were compared to 18 glaucomatous eyes of 18 patients (POAG group I, mean age 55 +/- 11 years) and 59 glaucomatous eyes of 59 patients (POAG group II, mean age 55 +/- 10 years). In the eyes of POAG group I and POAG group II, both juxtapapillary retinal blood flow and neuroretinal rim area blood flow were significantly decreased compared to an age-matched control group: neuroretinal rim area "flow" POAG group I -65%, POAG group II -66%; juxtapapillary retina "flow" POAG group I -52%, POAG group II -44%. All eyes of the POAG group I (MD < 2 dB) and 56 of 61 eyes of the POAG group II (MD > = 2 dB) showed a retinal perfusion lower than the 90% percentile of normal blood flow. We found no correlation between reduction of juxtapapillary or papillary blood flow and mean defect in POAG eyes. Glaucomatous eyes with no defects or borderline visual field defects as well as glaucomatous eyes in an advanced disease stage show significantly decreased optic nerve head and juxtapapillary retinal capillary blood flow.

Interactions Between Nitric Oxide and Angiotensin II on Renal Cortical and Papillary Blood Flow

This study examined the role of angiotensin II (Ang II) on the effects of nitric oxide (NO) synthesis blockade on renal cortical and papillary blood flow in innervated and denervated kidneys of volume-expanded Munich-Wistar rats with hormonal influences on the kidney that were held constant by intravenous infusion. Cortical (CBF) and papillary (PBF) blood flow were measured by laser-Doppler flowmetry. A low dose of N omega-nitro-L-arginine methyl ester (L-NAME, 3.7 nmol x kg[-1] x min[-1]) reduced CBF only in innervated kidneys, and this effect was abolished by subsequent administration of valsartan (an AT1 antagonist). L-NAME 3.7 nmol x kg(-1) x min(-1) improved PBF autoregulation by lowering PBF to the range of 100 to 140 mm Hg of perfusion pressure, and this effect was attenuated or abolished by valsartan in innervated and denervated kidneys, respectively. These results indicate that the cortical and medullary vasoconstriction induced by a low dose of L-NAME are caused by potentiation of the vasoconstrictor influence of renal sympathetic nerves and Ang II. A higher dose of L-NAME (37 nmol x kg[-1] x min[-1]) lowered CBF and PBF in both innervated and denervated kidneys. This effect of L-NAME on the cortical circulation was abolished by valsartan, but this AT1 antagonist had no effect on the medullary vasoconstriction produced by NO synthesis blockade. Therefore, a higher dose of L-NAME induces a renal cortical vasoconstriction through potentiation of the renin-angiotensin system, whereas the fall of PBF seen after L-NAME 37 nmol x kg(-1) x min(-1) seems to be caused primarily by NO suppression. This Ang II potentiation produced by L-NAME in the renal cortex seems to be mediated by AT1 receptors, because it was unaffected by PD123319 (an AT2 antagonist). The results of the present study indicate that NO is an important modulator of the vasoconstrictor influence of Ang II in the renal cortical circulation of the rat. However, although there are some interactions between NO and renal nerves and Ang II on the medullary circulation, the renal medullary vasoconstriction produced by L-NAME appears to be caused primarily by NO suppression, with little influence of the renal vasoconstrictor systems.

Importance of nitric oxide and prostaglandins in the control of rat renal papillary blood flow.

The role of nitric oxide and prostaglandins in the control of rat renal papillary blood flow has been studied in anesthetized Munich-Wistar rats by use of laser Doppler flowmeter. Acute administration of N omega-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg IV (n=8) increased mean arterial pressure by 27.8 +/- 3.6%, decreased papillary blood flow by 39.4 +/- 3.8%, and decreased renal blood flow by 47.4 +/- 1.9%. The subsequent administration of indomethacin (7.5 mg/kg IV) further decreased papillary blood flow (35.2 +/- 2.5%) without significant changes in mean arterial pressure or renal blood flow. In a second group (n = 6), administration of indomethacin before L-NAME decreased papillary blood flow by 39.6 +/- 2.1% without significantly altering mean arterial ressure or renal blood flow. The subsequent injection of L-NAME further decreased papillary blood flow (32.9 +/- 1.8%) and renal blood flow (49.8 +/- 6.6%) while increasing mean arterial pressure to a level not significantly different from that found in the first group. Autoregulation studies showed that L-NAME but not indomethacin reduced the renal perfusion pressure-renal blood flow relationship without altering autoregulation. However, both nitric oxide and prostaglandins importantly affected the renal perfusion pressure-papillary blood flow relationship because L-NAME and indomethacin significantly decreased this relationship in an additive fashion. Although both drugs reduced the sensitivity of the pressure-papillary flow relationship, only L-NAME affected autoregulation so that papillary blood flow was autoregulated at higher renal perfusion pressures. Thus, the present results indicate that both nitric oxide and prostaglandins control a similar percentage of rat renal papillary blood flow, but nitric oxide seems to be more important than prostaglandins as a mediator of the pressure-blood flow relationship. In contrast, only nitric oxide modifies the renal blood flow level, although it does not disturb whole-kidney blood flow autoregulation.

Efferent renal sympathetic nerve stimulation in vivo. Effects on regional renal haemodynamics in the Wistar rat, studied by laser-Doppler technique.

Intrarenal blood flow regulation probably affects long-term blood pressure homeostasis. We have previously shown that 5 Hz renal sympathetic stimulation inhibits a humoral renal depressor mechanism, otherwise activated when increasing perfusion pressure to an isolated kidney in a cross-circulation set-up. This inhibition was suggested to occur as a result of a reduction of renomedullary blood flow. Little is known about nervous blood flow regulation within the medulla. Therefore in this study, total renal (RBF), cortical (CBF) and papillary (PBF) blood flows were separately measured by ultrasonic and laser-Doppler techniques in Wistar rats during graded renal sympathetic stimulations. Periods of 15 min stimulation at 0.5, 2 and 5 Hz were performed in random order. RBF decreased at 0.5 Hz by 1%, at 2 Hz by 16% (P < 0.001) and at 5 Hz by 49% (P < 0.001). In a similar fashion (r = 0.73, P < 0.001), CBF decreased by 1%, 10% (P < 0.001) and 37% (P < 0.001), respectively. By contrast, PBF increased by 2% at 0.5 Hz and 4% at 2 Hz, while it decreased at 5 Hz, by 4% (P < 0.05, compared with 2 Hz). It seems therefore, that superficial renocortical and total renal blood flows are closely regulated by renal sympathetic nerves with increasing vasoconstriction at higher frequencies, while medullary blood flow, on the other hand, seems to be under strong local control, tending to offset neurogenic flow restrictions.

Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip hypertension.

To examine the role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip (1-K,1C) hypertension in rats. The stimulus for the release of an antihypertensive lipid from the kidney is not known. This study examined whether cortical or papillary blood flow is altered after removal of the clip from the renal artery of 1-K,1C hypertensive rats, and the effects of blockade of the renal metabolism of arachidonic acid by P-450 with 17-octadecynoic acid (17-ODYA) on the fall in blood pressure. Cortical and medullary blood flows were measured using laser-Doppler flowmetry. 17-ODYA (33 nmol/min) was infused directly into the renal artery to examine the effect of inhibition of renal P-450 activity on reversal of 1-K,1C hypertension. The renal metabolism of arachidonic acid in control and in 1-K,1C hypertensive rats was assessed by incubating microsomes with [14C]-arachidonic acid, the metabolites formed being measured using reverse-phase high-performance liquid chromatography. The antihypertensive effects of these P-450 metabolites of arachidonic acid were compared with those of medullipin I after intravenous administration in conscious spontaneously hypertensive rats (SHR). Cortical and papillary blood flow increased significantly and arterial pressure fell after unclipping the renal artery in the 1-K,1C hypertensive rats. 17-ODYA prevented the fall in blood pressure after unclipping. The production of epoxy- and dihydroxy-eicosatrienoic acids was elevated in microsomes prepared from the renal cortex of the 1-K,1C hypertensive rats. However, intravenous administration of these metabolites did not mimic the effect of medullipin I to lower arterial pressure in SHR. Elevations in renal cortical or papillary blood flow, or both, may stimulate the release of a P-450-derived antihypertensive lipid from the kidney after unclipping of the renal artery in 1-K,1C hypertensive rats. However, it is unlikely that this substance is a P-450 metabolite of arachidonic acid.

Role of Nitric Oxide on Papillary Blood Flow and Pressure Natriuresis

This study examined whether nitric oxide synthesis blockade or potentiation (with N omega-nitro-L-arginine methyl ester [L-NAME] or N-acetylcysteine, respectively) can shift the relations between sodium excretion, papillary blood flow, and renal perfusion pressure. Papillary blood flow was measured by laser Doppler flowmetry. A low dose of L-NAME (3.7 nmol/kg per minute) reduced papillary blood flow only at high arterial pressure (140 mm Hg), but it had no effect on pressure natriuresis. Infusion of 37 nmol/kg per minute L-NAME reduced cortical blood flow by 9% at all perfusion pressures studied, lowered papillary blood flow by 8% and 19% at 120 and 140 mm Hg, respectively, and blunted the pressure-natriuresis response. The administration of 185 nmol/kg per minute L-NAME reduced cortical blood flow by 30% and decreased papillary blood flow by 25% in the range of 100 to 140 mm Hg of arterial pressure. Blockade of nitric oxide synthesis with L-NAME at all doses studied reduced papillary blood flow only at high renal perfusion pressures, but papillary blood flow remained essentially unchanged at low perfusion pressures, thus restoring papillary blood flow autoregulation. N-Acetyl-cysteine (1.8 mmol/kg) increased papillary blood flow by 9% and shifted the relations between papillary blood flow, sodium excretion, and renal perfusion pressure toward lower pressures. This effect of N-acetylcysteine on papillary blood flow was blocked by subsequent L-NAME administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization and regulation of angiotensin II receptors in renomedullary interstitial cells

The renin-angiotensin system has been implicated in regulating renal medullary and papillary microcirculation and urinary concentrating processes, but the mechanisms by which angiotensin II (Mg II) exerts its influences in the renal medulla are not well understood [1]. Although physiological studies demonstrated that medullary blood flow and/or papillary blood flow may be altered by dietary sodium intake [1], inhibition of Mg II formation by angiotensin converting enzyme inhibitors [2], and infusion of exogenous Mg II with or without blockade of Mg II receptors [3, 4], controversy remains with respect to whether Mg II directly or indirectly exerts its influences on renal medullary processes. Because the cortical and medullary vasculatures display different sensitivities to Ang II [4, 5], cortical and medullary blood flow may be independently regulated by different mechanisms. In the renal medulla, both circulating and intrarenal Mg II may act independently, or interact with other circulating vasoactive peptides and local humoral paracrine factors, such as atrial natriuretic peptide, endothelin, the kallikrein-kinin system, prostaglandins and nitric oxide, to regulate microcirculation and urinary concentrating and diluting processes. In view of the importance of Mg II in regulating renal medullary function, and in order to help elucidate the mechanisms of the actions of Mg II in the renal medulla, this article will review the localization and regulation of Mg II receptors in the renomedullary interstitial cells in the renal medulla.

Juxtamedullary microvascular responses to arginine vasopressin in rat kidney

Experiments were performed to determine the site of arginine vasopressin (AVP)-induced vascular resistance adjustments that result in decreases in papillary blood flow. Simultaneous measurements of luminal diameter and centerline erythrocyte velocity allowed estimation of single-vessel blood flow in in vitro blood-perfused juxtamedullary nephrons. AVP (0.1-1,000 pM) caused concentration-dependent reductions in outer medullary descending vasa recta (OMDVR) blood flow (10 pM) without altering OMDVR diameter. Afferent arteriolar diameter was significantly decreased by 1 pM AVP, whereas arcuate artery diameter was decreased by 100 pM AVP. Increasing the concentration of AVP to 1,000 pM resulted in significant reductions of vessel diameter in interlobular arteries, distal afferent arterioles, and efferent arterioles. The effects of AVP to decrease afferent arteriolar diameter and blood flow were blocked in the presence of V1 receptor antagonist. These data indicate that afferent arterioles exhibit the greatest sensitivity to the vasoconstrictor effects of AVP, whereas OMDVR appear insensitive. We conclude that the change in OMDVR blood flow produced by AVP is not due to a direct effect of the peptide on this vascular segment but to its effect on upstream vessels.

Inhibition of renal vascular 20-HETE production impairs autoregulation of renal blood flow.

The present study evaluated the role of endogenous P-450 metabolites of arachidonic acid (AA) on autoregulation of renal blood flow in rats. Whole kidney and cortical blood flows were well autoregulated when renal perfusion pressure was varied from 150 to 100 mmHg. Infusion of 17-octadecynoic acid (17-ODYA) into the renal artery (33 nmol/min) increased cortical and papillary blood flows by 12.6 +/- 2.5 and 26.5 +/- 4.6%, respectively. After 17-ODYA, autoregulation of whole kidney and cortical blood flows was impaired. Intrarenal infusion of miconazole (8 nmol/min) had no effect on autoregulation of whole kidney, cortical, or papillary blood flows. 17-ODYA (1 microM) inhibited the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) and 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) by renal preglomerular microvessels in vitro by 83.7 +/- 7.4% and 89.0 +/- 4.9%, respectively. Miconazole (1 microM) reduced the formation of EETs by 86.4 +/- 5.7%, but it had no effect on the production of 20-HETE. These results suggest that endogenous P-450 metabolites of AA, particularly 20-HETE, may participate in the autoregulation of renal blood flow.

Kinin actions on renal papillary blood flow and sodium excretion.

Infusion of bradykinin into the renal medullary interstitium (0.1 micrograms/min, n = 6) significantly increased renal papillary blood flow as measured by laser-Doppler flowmetry to 117 +/- 3% of control without altering cortical blood flow or blood pressure in anesthetized Munich-Wistar rats. In animals prepared for clearance studies, renal medullary bradykinin infusion did not alter total renal blood flow, glomerular filtration rate, or renal interstitial hydrostatic pressure but increased urine flow by 100%, sodium excretion by 111%, and fractional sodium excretion by 107%. No changes occurred in mean arterial pressure or contralateral kidney function during the interstitial bradykinin infusion. Blockade of endogenous kinin degradation by interstitial infusion of captopril (1 mg/hr) significantly increased papillary blood flow by 21 +/- 5% without altering cortical blood flow. Pretreatment with the nitric oxide inhibitor NG-nitro-L-arginine-methyl ester (2 micrograms/min, n = 7) eliminated the increase in papillary blood flow associated with either bradykinin or captopril infusion. We conclude that renal medullary interstitial infusion of bradykinin increases sodium and water excretion, which is associated with a selective increase in papillary blood flow by a nitric oxide-dependent mechanism.