Endothelial prostaglandin D2 opposes angiotensin II contractions in mouse isolated perfused intracerebral microarterioles.

HYPOTHESIS: A lack of contraction of cerebral microarterioles to Ang II ("resilience") depends on cyclooxygenase (COX) and lipocalin type prostaglandin D sythase L-PGDS producing PGD2 that activates prostaglandin D type 1 receptors (DP1Rs) and nitric oxide synthase (NOS). MATERIALS & METHODS: Contractions were assessed in isolated, perfused vessels and NO by fluorescence microscopy. RESULTS: The mRNAs of penetrating intraparenchymal cerebral microarterioles versus renal afferent arterioles were >3000-fold greater for L-PGDS and DP1R and 5-fold for NOS III and COX 2. Larger cerebral arteries contracted with Ang II. However, cerebral microarterioles were entirely unresponsive but contracted with endothelin 1 and perfusion pressure. Ang II contractions were evoked in cerebral microarterioles from COX1 -/- mice or after blockade of COX2, L-PGDS or NOS and in deendothelialized vessels but effects of deendothelialization were lost during COX blockade. NO generation with Ang II depended on COX and also was increased by DP1R activation. CONCLUSION: The resilience of cerebral arterioles to Ang II contractions is specific for intraparenchymal microarterioles and depends on endothelial COX1 and two products that are metabolized by L-PGDS to generate PGD2 that signals via DP1Rs and NO.

High-salt diet induces outward remodelling of efferent arterioles in mice with reduced renal mass.

AIM: The glomerular filtration rate (GFR) falls progressively in chronic kidney disease (CKD) which is caused by a reduction in the number of functional nephrons. The dysfunctional nephron exhibits a lower glomerular capillary pressure that is induced by an unbalance between afferent and efferent arteriole. Therefore, we tested the hypothesis that oxidative stress induced by CKD differentially impairs the structure or function of efferent vs. afferent arterioles. METHODS: C57BL/6 mice received sham operations (sham) or 5/6 nephrectomy (RRM) and three months of normal- or high-salt diet or tempol. GFR was assessed from the plasma inulin clearance, arteriolar remodelling from media/lumen area ratio, myogenic responses from changes in luminal diameter with increases in perfusion pressure and passive wall compliance from the wall stress/strain relationships. RESULTS: Mice with RRM fed a high salt (vs. sham) had a lower GFR (553 ± 25 vs. 758 ± 36 µL min-1  g-1 kidney, P < 0.01) and a larger efferent arteriolar diameter (9.6 ± 0.8 vs. 7.4 ± 0.7 µm, P < 0.05) resulting in a lower media/lumen area ratio (1.4 ± 0.1 vs. 2.4 ± 0.2, P < 0.01). These alterations were corrected by tempol. The myogenic responses of efferent arterioles were about one-half that of afferent arterioles and were unaffected by RRM or salt. Passive wall compliance was reduced by high salt in both afferent and efferent arterioles. CONCLUSION: A reduction in renal mass with a high-salt diet induces oxidative stress that leads to an outward eutrophic remodelling in efferent arterioles and reduced wall compliance in both afferent and efferent arterioles. This may contribute to the lower GFR in this model of CKD.

Increased hydrogen peroxide impairs angiotensin II contractions of afferent arterioles in mice after renal ischaemia-reperfusion injury.

AIM: Renal ischaemia-reperfusion injury (IRI) increases angiotensin II (Ang II) and reactive oxygen species (ROS) that are potent modulators of vascular function. However, the roles of individual ROS and their interaction with Ang II are not clear. Here we tested the hypothesis that IRI modulates renal afferent arteriolar responses to Ang II via increasing superoxide (O2-) or hydrogen peroxide (H2 O2 ). METHODS: Renal afferent arterioles were isolated and perfused from C57BL/6 mice 24 h after IRI or sham surgery. Responses to Ang II or noradrenaline were assessed by measuring arteriolar diameter. Production of H2 O2 and O2- was assessed in afferent arterioles and renal cortex. Activity of SOD and catalase, and mRNA expressions of Ang II receptors were assessed in pre-glomerular arterioles and renal cortex. RESULTS: Afferent arterioles from mice after IRI had a reduced maximal contraction to Ang II (-27±2 vs. -42±1%, P < 0.001), but retained a normal contraction to noradrenaline. Arterioles after IRI had a 38% increase in H2 O2 (P < 0.001) and a 45% decrease in catalase activity (P < 0.01). Contractions were reduced in normal arterioles after incubation with H2 O2 (-22±2 vs. -42±1%, P < 0.05) similar to the effects of IRI. However, the impaired contractions were normalized by incubation with PEG catalase despite a reduced AT1 R expression. CONCLUSIONS: Renal IRI in mice selectively impairs afferent arteriolar responses to Ang II because of H2 O2 accumulation that is caused by a reduced catalase activity. This could serve to buffer the effect of Ang II after IRI and may be a protective mechanism.

Repeated mixing and isolation: measuring chronic, intermittent stress in Holstein calves.

Objectives of this study were to determine the physiological effects of psychological stress applied to dairy calves and to test if molasses consumption could be used to validate that a stressed condition was achieved. Twenty male calves (3 wk old) received jugular catheters and were randomly assigned to control (CTR; n = 4 pens of 1 calf per pen) or social stress treatments (STR; n = 4 pens of 4 calves per pen). The STR treatment included 5 cycles of 24-h isolation followed by regrouping with unfamiliar animals for 48 h (over 15 d). An ACTH challenge (0.1 IU/kg of body weight) was used to determine adrenal fatigue. Peak and total cortisol concentrations were greater for STR calves until the ACTH challenge. After the ACTH challenge, CTR calf cortisol increased and STR calf cortisol continued to decrease, suggesting adrenal fatigue. The number of calves that became positive for fecal shedding of Salmonella after the acute stress of being moved and the number of calves that were positive after the move decreased with each move. Fifty-six percent of STR calves changed from negative to positive for shedding after the first move compared with 18.75% of STR calves remaining negative after the third move. Difference in fecal shedding of Enterobacteriaceae from samples taken before and after moving calves on d 6 was less than that on d 2, 3, and 5. Leukocyte counts were not different, but trends for day effects were detected for neutrophil and monocyte percentages. Molasses consumption was greater for STR calves on d 2 and 11, as was total consumption. Latency to lie after eating also increased as the study progressed; STR calves required more time to lie after eating on d 12 than on d 3, and latency to lie was greater for STR than CTR on d 4, 8, 12, and 14. The STR calves also stood more than the CTR calves in the 4-h afternoon period on d 4, 5, 7, and 14. However, during the 4-h morning observations on d 14 (ACTH challenge), CTR calves stood more than STR calves. This model induced chronic stress, as characterized by adrenal fatigue, which was confirmed by molasses consumption and behavior changes. Therefore, molasses consumption could be used to confirm social stress in experimental models.

Feeding behaviors of transition dairy cows fed glycerol as a replacement for corn.

Feed sorting is a natural behavior of dairy cows that can result in inconsistencies in the nutritive value of a total mixed ration (TMR). The objective of this study was to determine the effects of replacing high-moisture corn with glycerol on feed sorting and the feed intake pattern of transition dairy cows. Multiparous Holstein cows (n=26) were paired by expected calving date, housed in individual tie stalls, and fed diets containing either glycerol or high-moisture corn once daily from d -28 to +56 relative to calving. Glycerol was included at 11.5 and 10.8% of the ration dry matter for the pre- and postpartum diets, respectively. The feed consumption pattern was determined by measuring TMR disappearance during the intervals from 0 to 4 h, 4 to 8 h, 8 to 12 h, and 12 to 24 h relative to feed delivery. Feed sorting was determined on d -16, -9, 9, 16, and 51 relative to calving at 4, 8, 12 and 24 h after feeding. The TMR particle size profile was determined at feed delivery and at 4, 8, 12, and 24 after feed delivery by using the Penn State Particle Separator (Nasco, Fort Atkinson, WI) to yield long (>19 mm), medium (<19 mm, >8 mm), short (<8 mm, >1.18 mm), and fine (<1.18 mm) particles. Overall feed intake did not differ between diets and was 14.7±0.4 and 20.2±0.5 kg/d for the pre- and postpartum intervals, respectively. During the prepartum period, glycerol decreased the amount of feed consumed during the first 4h after feed delivery (7.22 vs. 5.59±0.35 kg; control vs. glycerol, respectively) but increased feed consumed from 12 through 24 h after feed delivery (2.22 vs. 3.82±0.35 kg; control vs. glycerol, respectively). Similar effects on the feed consumption pattern were observed after calving. During the prepartum period, cows fed the control diet sorted against long particles, whereas cows fed glycerol did not sort against long particles (77.2 vs. 101.5±3.50% of expected intake for control vs. glycerol; significant treatment effect). The data indicate that addition of glycerol to the TMR alters the feed consumption pattern to increase feed consumption late in the day at the expense of feed consumed immediately after feeding, and it reduces sorting behavior against long particles. Together, these may reduce diurnal variations in the rumen environment to promote greater rumen health in transition cows.

Role of the kidneys in resistant hypertension.

Resistant hypertension is a failure to achieve goal BP (<140/90 mm Hg for the overall population and <130/80 mm Hg for those with diabetes mellitus or chronic kidney disease) in a patient who adheres to maximum tolerated doses of 3 antihypertensive drugs including a diuretic. The kidneys play a critical role in long-term regulation of blood pressure. Blunted pressure natriuresis, with resultant increase in extracellular fluid volume, is an important cause of resistant hypertension. Activation of the renin-angiotensin-aldosterone system, increased renal sympathetic nervous system activity and increased sodium reabsorption are important renal mechanisms. Successful treatment requires identification and reversal of lifestyle factors or drugs contributing to treatment resistance, diagnosis and appropriate treatment of secondary causes of hypertension, use of effective multidrug regimens and optimization of diuretic therapy. Since inappropriate renal salt retention underlies most cases of drug-resistant hypertension, the therapeutic focus should be on improving salt depleting therapy by assessing and, if necessary, reducing dietary salt intake, optimizing diuretic therapy, and adding a mineralocorticoid antagonist if there are no contraindications.

Use of thermography to screen for subclinical bumblefoot in poultry.

Thermographic imaging is a noninvasive diagnostic tool used to document the inflammatory process in many species and may be useful in the detection of subclinical bumblefoot and other inflammatory diseases. Bumblefoot is a chronic inflammation of the plantar metatarsal or digital pads of the foot (pododermatitis), or both. It is one of the major health problems in birds including chickens and is responsible for significant economic losses in commercial poultry operations. Early diagnosis of bumblefoot is essential for the prevention of economical loss and the improvement of animal well-being. The object of this study was to determine the suitability of thermography for the identification of subclinical bumblefoot in chickens. Experiment 1 was designed to validate thermography as a tool for screening avian populations for bumblefoot. The plantar surface of the feet of 150 randomly selected hens was imaged using a thermal camera. The thermal images were identified as suspect, positive, or negative for bumblefoot based on thermal patterns of the plantar surface. Visual inspection of the feet identified as suspect followed 14 d later. A visual score of clinical, mildly clinical, or negative for bumblefoot was assigned, based on gross pathological changes in the plantar surface. A correlation between initial thermal images identified as suspect for bumblefoot and a visual score of positive 14 d later was 83% (P < 0.01). In experiment 2, hens whose feet were free of lesions were inoculated in the metatarsal foot pad with Staphylococcus aureus. Thermal images and visual clinical scores were taken, prechallenge and 1, 2, 3, 4, and 7 d postchallenge. The correlation between thermal images classified as clinical and a visual score of clinical for bumblefoot was 86.7% (P < 0.001). However, the correlation between the thermal images classified as mild (subclinical) and a visual score of mild was only 26.7%, suggesting that thermography is a more sensitive indicator of subclinical infection than visual appraisal. Thermography may thus provide a useful tool for screening avian populations for signs of bumblefoot, early in the course of the disease, which will improve recovery percentages and bird well-being.

Comparison of inhibitors of superoxide generation in vascular smooth muscle cells.

BACKGROUND AND PURPOSE: We compared the dose-dependent reductions in cellular superoxide anion (O(2)(-)) by catalytic agents: superoxide dismutase (SOD), polyethylene glycol (PEG)-SOD and the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (tempol) with uncharacterized antioxidants: 5,10,15,20-tetrakis (4-sulphonatophenyl) porphyrinate iron (III)(Fe-TTPS), (-)-cis-3,3',4',5,7-pentahydroxyflavane (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol (-epicatechin), 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) and N-acetyl-L-cysteine (NAC) with the spin trap nitroblue tetrazolium (NBT) and with the vitamins or their analogues: ascorbate, alpha-tocopherol and 6-hydroxy-2,5,7,8-tetramethylkroman-2-carboxy acid (trolox). EXPERIMENTAL APPROACH: O(2)(-) was generated in primary cultures of angiotensin II-stimulated preglomerular vascular smooth muscle cells from spontaneously hypertensive rats and detected by lucigenin-enhanced chemiluminescence. KEY RESULTS: SOD, PEG-SOD, NAC and tempol produced a similar maximum inhibition of O(2)(-) of 80-90%. -Epicatechin, NBT, ebselen and Fe-TTPS were significantly (P < 0.0125) less effective (50-70%), whereas trolox, alpha-tocopherol and ascorbate had little action even over 24 h of incubation (<31%). Effectiveness in disrupted and intact cells was similar for the permeable agents, PEG-SOD and tempol, but was enhanced for SOD. Generation of O(2)(-) was increased by NAC and NBT at low concentrations but reduced at high concentrations. CONCLUSIONS AND IMPLICATIONS: Maximum effectiveness against cellular production of O(2)(-) requires cell membrane permeability and catalytic action as exemplified by PEG-SOD or tempol. NAC and NBT have biphasic effects on O(2)(-) production. Vitamins C and E or analogues have low efficacy.

Short communication: effect of temporary glycosuria on molasses consumption in Holstein calves.

This study was conducted to determine the effect of experimentally increased glucose demand on voluntary consumption of molasses by dairy calves. Three-week-old calves received 0.365 g of phlorizin by s.c. injection. Urinary output and molasses consumption were measured hourly, and urinary glucose concentration was screened. Molasses consumption for the 24 h after treatment was (mean +/- SE) 72.0 g (+/-7) for the control group and 142 g (+/-1) for the phlorizin-treated group. Urinary output for the 8-h test period was 1.13 kg for the control group and 1.67 kg for the phlorizin-treated calves. Mean urinary glucose peaked at 10 g/L by 4 h after treatment for calves given phlorizin, whereas the concentration for the control group remained close to 0 g/L. Phlorizin treatment increased voluntary consumption of molasses in 3-wk-old Holstein calves.

Redox regulation of the afferent arteriole and tubuloglomerular feedback.

Oxidative stress implies an increased production of reactive oxygen species (ROS) or a decreased capacity to metabolize them. Superoxide anion (O) can bioinactivate nitric oxide (NO). Therefore, many effects of ROS are manifest as NO deficiency. The afferent arteriole and macula densa cell both contain a full complement of components of nicotine adenine dinucleotide phosphate (NADPH) oxidase that generates O. Nitric oxide synthase (NOS) type 1 or neuronal NOS (nNOS) is expressed in the macula densa and NOS type II or endothelial NOS (eNOS) in the afferent arteriole. Whole animal studies in models of hypertension and oxidative stress demonstrate that metabolism of O by a superoxide dismutase (SOD) mimetic can reduce renal vascular resistance. In vivo studies of single nephron function and in vitro studies with the double-perfused juxtaglomerular apparatus preparation have shown extensive interaction between O and NO in macula densa to regulate afferent arteriolar tone mediated by the tubuloglomerular feedback response. In vitro studies of rabbits isolated, perfused afferent arterioles have shown a similar interaction in this vessel. These data indicate important roles for O in the macula densa and afferent arterioles to enhance preglomerular resistance in animal models of oxidative stress. As an increase in afferent arteriolar resistance can precede hypertension, oxidative stress could be important in determining the long-term blood pressure and thereby contribute to hypertension.

Involvement of Cdc25A phosphatase in Hep3B hepatoma cell growth inhibition induced by novel K vitamin analogs.

We previously found that K vitamin analogues caused cell growth inhibition in Hep3B hepatoma cells in vitro, which was associated with their inhibitory effects on protein tyrosine-phosphatases. In this study, we show that Cdc25A, a protein phosphatase, was inactivated by novel arylating K vitamin analogues. The inactivation of Cdc25A correlated with their effects on cell growth inhibition. Cyclin-dependent kinase (Cdk) 4, an important regulator for G(1) progression, was found to be tyrosine-phosphorylated by the arylating analogues, and this phosphorylation was correlated with the inhibitory effects of the analogues on Cdc25A activity. Furthermore, Cdk4 dephosphorylation experiments showed that Compound (Cpd) 5, a prototype arylating analogue, inhibited Cdc25A-mediated Cdk4 dephosphorylation, whereas Cpd 26, a nonarylating vitamin K analogue, had no effect on this event. We also examined Cdk4 kinase activity using retinoblastoma protein as a substrate and found that Cpd 5 inhibited retinoblastoma protein phosphorylation in a concentration-dependent manner, indicating that Cdk4 activity was inhibited by Cpd 5 treatment. Moreover, the thiol-antioxidants glutathione and N-acetyl-L-cysteine antagonized the Cpd 5-induced Cdk4 tyrosine phosphorylation, whereas the nonthiol-antioxidants catalase and superoxide dismutase did not. These results suggest that Hep3B cell growth inhibition by these K vitamin analogues may be related in part to inactivation of Cdc25A activity and support the hypothesis that Cdc25A is an attractive target for drugs designed to inhibit cancer cell growth.

The SOD mimetic tempol restores vasodilation in afferent arterioles of experimental diabetes.

BACKGROUND: Endothelium-dependent vasodilation is impaired in large conduit vessels in diabetes mellitus. Oxygen radicals contribute to the impaired endothelium-dependent vasodilation. We tested the hypothesis that stimulated endothelium-dependent vasodilation is reduced in renal afferent arterioles in diabetes and is caused by an increase in vascular superoxide (O2(-)). METHODS: Renal afferent arterioles from normal and insulin-treated alloxan-diabetic rabbits were microdissected and microperfused in vitro for the study of luminal diameter responses to acetylcholine (Ach; 10(-11) to 10(-6) mol/L). The blood glucose concentration of insulin-treated alloxan-diabetic rabbits was elevated fourfold compared with normal rabbits (319 +/- 23 vs. 79 +/- 6 mg/dL, P < 0.001). RESULTS: In norepinephrine (NE)-preconstricted afferent arterioles of normal rabbits, Ach significantly (P < 0.001) increased luminal diameter by 165 +/- 44%. The nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (10(-4) mol/L) blocked this Ach-induced vasodilation. In marked contrast, in NE-preconstricted arterioles of diabetic rabbits, Ach significantly (P < 0.01) decreased luminal diameter by 41 +/- 11%. Pretreatment of diabetic afferent arterioles with the superoxide dismutase (SOD) mimetic tempol (10(-3) mol/L) restored a vasodilator response to Ach. In NE-preconstricted diabetic afferent arterioles treated with tempol, Ach significantly (P < 0.001) increased luminal diameter by 25 +/- 6%. CONCLUSIONS: Ach-induced afferent arteriolar vasodilation is dependent on nitric oxide and is impaired in diabetes. O2(-) contributes to the impaired Ach-induced vasodilation in renal afferent arterioles in diabetes.

Effects of dietary salt intake on plasma arginine.

Because L-arginine is degraded by hepatic arginase to ornithine and urea and is transported by the regulated 2A cationic amino acid y(+) transporter (CAT2A), hepatic transport may regulate plasma arginine concentration. Groups of rats (n = 6) were fed a diet of either low salt (LS) or high salt (HS) for 7 days to test the hypothesis that dietary salt intake regulates plasma arginine concentration and renal nitric oxide (NO) generation by measuring plasma arginine and ornithine concentrations, renal NO excretion, and expression of hepatic CAT2A, and arginase. LS rats had lower excretion of NO metabolites and cGMP, lower plasma arginine concentration (LS: 83 +/- 7 vs. HS: 165 +/- 10 micromol/l, P < 0.001), but higher plasma ornithine concentration (LS: 82 +/- 6 vs. HS: 66 +/- 4 micromol/l, P < 0.05) and urea excretion. However, neither the in vitro hepatic arginase activity nor the mRNA for hepatic arginase I was different between groups. In contrast, LS rats had twice the abundance of mRNA for hepatic CAT2A (LS: 3.4 +/- 0.4 vs. HS: 1.6 +/- 0.5, P < 0.05). The reduced plasma arginine concentration with increased plasma ornithine concentration and urea excretion during LS indicates increased arginine metabolism by arginase. This cannot be ascribed to changes in hepatic arginase expression but may be a consequence of increased hepatic arginine uptake via CAT2A.

AT1 receptor antagonist combats oxidative stress and restores nitric oxide signaling in the SHR.

The tubuloglomerular feedback (TGF) responses of the spontaneously hypertensive rat (SHR) are under exaggerated regulation by angiotensin II (Ang II) type 1 receptors (AT1-R). Since AT1-Rs enhance oxygen radical (O2-) generation, we tested the hypothesis that the exaggerated TGF was due to a diminished blunting by macula densa (MD)-derived nitric oxide (NO) because of excessive AT1-R-dependent generation of O2-. Groups of SHR and control Wistar-Kyoto (WKY) rats received vehicle (Veh), the AT1-R antagonist candesartan (Cand; 3 mg. kg-1. day-1), or nonspecific therapy with hydralazine + hydrochlorothiazide + reserpine (HHR) for two weeks. Compared with WKY rats, the elevated mean arterial pressure of SHR (WKY 125 +/- 2 vs. SHR 163 to 779 mm Hg, P < 0.001) was reduced (P < 0.001) similarly in SHR by Cand and HHR (121 +/- 5 and 116 +/- 5 mm Hg, P = NS). The SHR had an increased maximal TGF response (change in stop flow pressure during luminal perfusion of fluid: SHR 11.2 +/- 0.5 vs. WKY 8.3 +/- 0.4 mm Hg, P < 0.01) and a reduced TGF response to blockade of neuroneal NO synthase (nNOS) in the MD with luminal 7-nitroindazole (7-NI: DeltaTGF in WKY 2.8 +/- 0.4 vs. SHR 1.1 +/- 0.6 mm Hg, P < 0.05). Although the elevated TGF responses of SHR were normalized by both HHR and Cand, only Cand restored a normal TGF response to luminal perfusion of the MD with 7-NI (DeltaTGF with 7-NI in SHR: Veh + 1.8 +/- 0.4 vs. Cand + 3.4 +/- 0.5 mm Hg, P < 0.05). To abrogate the local effects of O2-, tempol (a membrane-permeable superoxide dismutase mimetic) was perfused into the efferent arteriole. During tempol, SHR given vehicle or HHR had a much increased response to blockade of nNOS with 7-NI (DeltaTGF in SHR with 7-NI during tempol: Veh 6.3 +/- 1.0 and HHR 4.5 +/- 0.8 mm Hg, P < 0.01 vs. no tempol for both), implying that the effects of NO had been prevented because of excessive O2-. In contrast, the TGF response to 7-NI in SHR given Cand was unaffected by tempol (DeltaTGF with 7-NI during tempol: 2.9 +/- 0.9, P = NS, compared with no tempol). In conclusion, TGF responses of SHR are exaggerated because of the effects of hypertension and AT1-R. AT1-R blockade specifically diminishes oxidative stress and restores NO signaling in the juxtaglomerular apparatus of the SHR.

Renal artery stenosis: a common, treatable cause of renal failure?

Chronic azotemic renovascular disease is common in patients with atherosclerosis. Its prevalence appears to be increasing in the aging population. How often it is the primary cause of end-stage renal disease (ESRD) is not yet certain. Some studies suggest that 10%-40% of elderly hypertensive patients with newly documented ESRD and no demonstrable primary renal disease have significant renal artery stenosis (RAS). Atherosclerotic vascular occlusive disease of the renal arteries does progress, but current rates of progression and occlusion are lower than those reported a decade ago. Methods of identifying patients whose renal function is at true risk from vascular occlusive disease and determining who will benefit from intervention remain elusive. The presence of RAS in an azotemic patient can be assessed with noninvasive and risk-free radiologic techniques, including Duplex doppler velicometry and magnetic resonance angiography. Functional tests that predict the change in renal function after revascularization are not yet available. However, a renal length of greater than 7.5 cm in the absence of renal cysts and a short history of renal functional deterioration indicate a good prognosis. Patients with recent deterioration in renal function, those with bilateral renal artery stenosis or stenosis to a single functioning kidney, those with flash pulmonary edema, advanced chronic renal failure, or ESRD (who have much to gain), those with reversible azotemia during angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB) therapy, and those whose conditions cannot be managed medically should be considered for revascularization. Results from recent controlled clinical trials of the response to percutaneous transluminal renal artery angioplasty (PTRA) and stenting indicate that improvement in blood pressure control or renal function is not a predictable outcome of renal revascularization. In azotemic groups, 25%-30% of patients achieve important recovery of renal function. Thus, significant progress has been made recently in determining whether RAS is a frequent, treatable cause of renal failure. The decision to recommend revascularization remains a difficult balance between the risks and expense of the procedure and the undoubted benefits that accrue if renal function is successfully stabilized.

Nephron pO2 and renal oxygen usage in the hypertensive rat kidney.

BACKGROUND: The kidney has a high rate of oxygen usage (QO2) that is closely dependent on tubular Na+ transport (TNa). However, little is known concerning the regulation of the cortical partial pressure of oxygen (pO2). METHODS: First, the pO2 was measured in the outer cortical proximal (PT) and distal tubules (DT), efferent arterioles (EA), and superficial (SC) and deep cortical (DC) tissues in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs) using an ultramicrocoaxial O2 electrode. We next assessed the determinants of QO2 and tubular reabsorption of sodium (TNa) for whether they could account for any differences in renal cortical pO2 in SHRs. RESULTS: The pO2 in the EA was reduced 40 to 50% compared with arterial values but was similar in the two strains (WKY rats 45 +/- 2 vs. SHRs 41 +/- 1 mm Hg, P = NS). The pO2 value in the PT, DT, and SC did not differ within strains. All were significantly (P < 0. 001) lower in SHRs (for example, pO2 in PT of WKY rats 39 +/- 1 vs. SHRs, 30 +/- 1 mm Hg). The pO2 in the renal vein was above that at any site in the EA or the cortex, implying a precapillary shunting of O2 from the artery to vein. SHRs had reduced renal blood flow (RBF) leading to a reduced (P < 0.05) rate of O2 delivery (WKY rats 42 +/- 6 vs. SHRs 30 +/- 1 micromol. min-1. g-1) and a reduced glomerular filtration rate, leading to a lower (P < 0.001), TNa (WKYs 115 +/- 9 vs. SHRs 66 +/-8 micromol. min-1. g-1). However, despite the 43% reduction in TNa, the renal O2 usage was not significantly different between strains (WKY rats 7.6 +/- 0.8 vs. SHRs 9.0 +/- 1.0 micromol. min-1. g-1). Therefore, the SHRs had a sharp reduction (P < 0.001) in the O2 efficiency for Na+ reabsorption (TNa/QO2; WKY rats 15.1 +/- 1.6 vs. SHRs 7.3 +/-1.0 micromol-1). CONCLUSIONS: A precapillary O2 shunt reduces the pO2 of cortical nephrons. The pO2 is reduced further in SHRs because of less efficient O2 usage for Na+ transport.

A novel precipitating auxiliary approach to the purification of Baylis-Hillman adducts.

Diaryl alkene alcohol 1 is a 'precipiton', a precipitating auxiliary that is used to aid the isolation of Baylis-Hillman adducts.

Renal expression of constitutive NOS and DDAH: separate effects of salt intake and angiotensin.

BACKGROUND: Nitric oxide (NO) is generated from NO synthase (NOS) isoforms. These enzymes can be inhibited by asymmetric dimethylarginine, which is inactivated by N(G)-N(G)-dimethylarginine dimethylaminohydrolase (DDAH). The neuroneal (nNOS) type I and endothelial (eNOS) type III constitutive NOS isoforms are expressed predominantly in the macula densa and microvascular endothelium of the renal cortex, respectively. DDAH is expressed at sites of NOS expression. Since NO may coordinate the renal responses to angiotensin II (Ang II) and changes in salt intake, we tested the hypothesis that salt intake regulates the expression of nNOS, eNOS and DDAH by Ang II acting on type 1 (AT(1)) receptors. METHODS: Groups (N = 6) of rats were adapted to low-salt (LS) or high-salt (HS) intakes for 10 days. Other groups of LS and HS rats received the AT(1) receptor antagonist losartan for six days (to test the effects of salt independent of AT(1) receptors). A further group of HS rats received an infusion of Ang II for six days (to test the effect of Ang II independent of salt intake). RESULTS: Compared with HS rats, there was a significant (P < 0.05) increase in LS rats of nNOS protein in kidney and immunohistochemical expression in the macula densa, and of eNOS protein expression and immunohistochemical expression in the microvascular endothelium, and of DDAH protein expression. Losartan prevented these effects of salt on the expression of eNOS or DDAH, both of which were also increased by Ang II infusions in HS rats. In contrast, losartan did not prevent the effects of salt on nNOS expression, which was unresponsive to Ang II infusion. The generation of NO(2)(-) released by slices of renal cortex, in the presence of saturating concentrations of L-arginine, was increased by LS, compared to HS, independent of losartan and by Ang II during HS. CONCLUSION: The expressions of eNOS in cortical microvascular endothelium and DDAH in kidney are enhanced by Ang II acting on AT(1) receptors. The expression of nNOS in the macula densa is enhanced by salt restriction independent of Ang II or AT(1) receptors.