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C S Wilcox

Publications and source records attributed to C S Wilcox.

At least 37 records · Page 2Linked to original sources
PubMed1999

Determination of reduced and oxidized homocysteine and related thiols in plasma by thiol-specific pre-column derivatization and capillary electrophoresis with laser-induced fluorescence detection.

A new sensitive and rapid capillary electrophoresis (CE) assay for measuring reduced and oxidized thiols in human plasma has been developed. To prevent oxidation of the thiols, whole blood was immediately centrifuged after collection and the plasma proteins were precipitated with perchloric acid. The reduced thiols in the supernatant were derivatized quantitatively at 25 degrees C, pH 7.5 with a fluorescent reagent, fluorescein-5-maleimide (FM). The total plasma concentration of thiols, including the fraction coupled to proteins, was assayed after an initial reduction of the disulfide linkage in plasma with dithiothreitol. The separation of FM-thiols was performed in an acetonitrile/10 mM sodium phosphate-50 mM SDS buffer [25:75 (v/v); pH 7.0] using a fused-silica capillary (57 cm x 75 microm I.D.) at 45 degrees C. A 3-mW argon-ion laser (lambda(ex) 488 nm/lambda(em) 520 nm) was employed for FM-thiol detection. With the electric field of 530 V/cm, the time needed for the separation of FM-homocysteine, FM-glutathione and FM-N-acetylcysteine was less than 8 min. The lower limit of detection was 3 microM for the total thiols and 10 nM for the reduced thiols. The method was applied to, the determination of homocysteine levels in plasma from patients with end-stage renal disease.

Acetylcysteine↗
PubMed1999

Inhibition of hepatoma cell growth in vitro by arylating and non-arylating K vitamin analogs. Significance of protein tyrosine phosphatase inhibition.

We recently found that a thioether analog of K vitamin (Cpd 5) inhibited the activity of protein-tyrosine phosphatases (PTPases) and induced protein-tyrosine phosphorylation in a human hepatoma cell line (Hep3B). We have now examined the structural requirements for induction of protein-tyrosine phosphorylation and PTPase inhibition by several K vitamin analogs. Thioether analogs with sulfhydryl arylation capacity, especially those with a hydroxy (Cpd 5) or a methoxy group at the end of the side chain, induced protein-tyrosine phosphorylation, but non-arylating analogs, such as those with an all-carbon or O-ether side chain, did not. Among the receptor-tyrosine kinases, epidermal growth factor receptors were tyrosine-phosphorylated by treatment with thioether analogs, whereas insulin and hepatocyte growth factor receptors were not. An increase in tyrosine-phosphorylated ERK2 mitogen-activated protein kinase was also observed. The activity of purified T cell PTPase was inhibited only by the thioether analogs, but not by non-arylating analogs. Furthermore, the epidermal growth factor receptor dephosphorylation activity of Hep3B cell lysates was inhibited by Cpd 5 treatment. A similar induction of protein-tyrosine phosphorylation by Cpd 5 was seen in other human hepatoma cell lines together with growth inhibition. However, one cell line (HepG2), which was relatively resistant to growth inhibition by Cpd 5, did not increase its phosphorylation levels upon Cpd 5 treatment. These results suggest that cell growth inhibition by thioether analogs is closely associated with inhibition of PTPases by sulfhydryl arylation and with tyrosine phosphorylation of selected proteins.

Carcinoma, Hepatocellular↗
PubMed1999

Distribution of postsynaptic density proteins in rat kidney: relationship to neuronal nitric oxide synthase.

BACKGROUND: Neuronal nitric oxide synthase (nNOS) is expressed in skeletal muscle beneath the sarcolemma associated with dystrophin complex. In brain, nNOS is anchored to synaptic membranes by specific postsynaptic density proteins (PSD)-95 and PSD-93. We have investigated the cellular and subcellular localization of these PSD proteins in the kidney and their relationship to nNOS and the cell membrane. METHODS: Kidneys from male Sprague-Dawley rats were processed for light and electron microscopic immunohistochemistry with polyclonal antibodies against PSD and nNOS proteins. RESULTS: Western blot analysis of rat kidney revealed a specific band for PSD-93 at the molecular weight of 103 kDa. Immunostaining for PSD-93 was located in the thick ascending limb of the loop of Henle, macula densa cells, distal convoluted tubules, cortical collecting ducts, outer and inner medullary collecting duct, glomerular epithelium, and Bowman's capsule. A pre-embedding electron microscopic immunoperoxidase procedure localized PSD-93 to the basolateral membrane of these tubular cells. Using different sized immunogold particles, a portion of nNOS in the macula densa colocalized with PSD-93 adjacent to cytoplasmic vesicles and the basolateral membrane. In contrast, PSD-95 protein was detected only weakly in the cortex by Western blot. Immunostaining for PSD-95 was located only faintly in the apical membrane of the thick ascending limb, macula densa, distal convoluted tubule and cortical collecting duct cells. CONCLUSION: PSD-93 is the predominant PSD expressed in the rat kidney. It is located primarily in the basolateral membranes of distal nephron and colocalizes with a pool of nNOS in cytoplasmic vesicles and basolateral membranes of macula densa cells.

Animals↗
PubMed1999

Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression.

The efficacy of nefazodone in prevention of relapse of depression was evaluated in a 36-week double-blind, placebo-substitution, continuation treatment trial. After 16 weeks of acute, single-blind treatment with nefazodone, 131 patients responding to treatment and in stable remission were randomized in a 36-week double-blind trial to either nefazodone (n = 65) or placebo (n = 66). Patients were defined as having relapsed if they had a total score > or = 18 on the 17-item Hamilton Depression Scale on two consecutive visits or if they discontinued treatment for lack of efficacy. Relapse rates were significantly lower for patients randomized to continued nefazodone treatment than for patients switched to placebo. Kaplan-Meier estimates of relapse rates 9 months (36 weeks) after the end of acute treatment were 1.8% for nefazodone versus 18.3% for placebo (P = 0.009) by the Hamilton Depression Scale and 17.3% versus 32.8% (P = 0.028) by discontinuation for lack of efficacy. The mean modal dose of nefazodone was 412 mg/day at study endpoint. These results demonstrate the clinical effectiveness of up to 1 year's treatment (16 weeks acute and 36 weeks continuation) with nefazodone in depressed patients. Long-term efficacy of nefazodone was accompanied by a good safety profile without any weight gain and with minimal symptoms of withdrawal upon abrupt discontinuation of treatment.

Adult↗
PubMed1999

Nitric oxide synthase in the JGA of the SHR: expression and role in tubuloglomerular feedback.

The spontaneously hypertensive rat (SHR) has an enhanced tubuloglomerular feedback (TGF) and a diminished buffering by juxtaglomerular apparatus (JGA)-derived NO. We examined the hypothesis that these effects are due to decreases in nitric oxide synthase (NOS) expression or limited availability of L-arginine or tetrahydrobiopterin (BH(4)). SHR had significantly (P < 0.05) greater mRNA abundance (by RT-PCR) or protein (by Western analysis) for neuronal NOS (nNOS, or type I) and endothelial cell NOS (ecNOS, or type III) in renal cortex or isolated glomeruli, respectively. There was prominent expression of ecNOS in glomerular endothelium and nNOS in macula densa. Maximal TGF responses, assessed from changes in proximal stop-flow pressure during orthograde loop of Henle (LH) perfusion, were greater in SHR [Wistar-Kyoto (WKY), 8.1 +/- 0.3 (n = 46) vs. SHR, 10.3 +/- 0.3 mmHg (n = 57); P < 0.001]. Unlike WKY, TGF responses of SHR were unresponsive to microperfusion of the nNOS inhibitor, 7-nitroindazole (7-NI, 10(-4) M) [WKY, 9.5 +/- 0.5 to 13.2 +/- 0.7 (n = 13, P < 0.001) vs. SHR, 11.8 +/- 0.7 to 12.5 +/- 0.6 mmHg (n = 19, not significant)], or to L-arginine (10(-3) M) [WKY, 7.7 +/- 0.8 to 6.3 +/- 0.4 (n = 10, P < 0.05) vs. SHR, 10.4 +/- 0.7 to 10.6 +/- 0.7 mmHg (n = 10, not significant)]. Neither BH(4) (10(-4) M) nor sepiapterin (10(-4) M), its stable precursor, modified TGF responses in WKY or in SHR, nor did they restore a response to microperfusion of 7-NI in SHR. In conclusion, there is a diminished role for NO from nNOS in blunting of TGF in SHR which cannot be ascribed to limited NOS expression or availability of substrate or BH(4).

Animals↗
PubMed1999

Two-week administration of tempol attenuates both hypertension and renal excretion of 8-Iso prostaglandin f2alpha.

8-Iso prostaglandin F2alpha (8-ISO) is formed nonenzymatically from the attack of superoxide radical on arachidonic acid. Therefore, 8-ISO is a marker of oxidative stress in vivo. We have recently shown that short-term administration of the membrane-permeable, metal-independent superoxide dismutase mimetic tempol (4-hydroxy-2, 2, 6, 6-tetramethyl piperidinoxyl) normalizes blood pressure in spontaneously hypertensive rats (SHR). The present study was designed to test whether prolonged administration of tempol ameliorates oxidative stress and hypertension in SHR. In control SHR (n=8), mean arterial pressure and heart rate were increased and renal blood flow and glomerular filtration rate were reduced compared with control Wistar-Kyoto rats (WKY) (n=7). Twenty-four-hour renal excretion of 8-ISO was significantly increased in SHR compared with WKY. Two weeks of tempol administration in the drinking water (1 mmol/L) to SHR (n=8) decreased mean arterial pressure by 18% (162+/-8 to 134+/-6 mm Hg, P<0.05), increased glomerular filtration rate by 17% (1.6+/-0.2 to 1. 9+/-0.3 mL/min), and decreased renal excretion of 8-ISO by 39% (9. 8+/-0.7 to 6.0+/-0.7 ng/24 hours, P<0.05). In contrast, tempol administration to WKY (n=6) had no significant effect on mean arterial pressure (115+/-5 versus 118+/-8 mm Hg), glomerular filtration rate (3.0+/-0.4 versus 2.5+/-0.5 mL/min), or renal excretion of 8-ISO (7.9+/-0.4 versus 6.8+/-0.7 ng/24 hours). In conclusion, the SHR is a model of hypertension and renal vasoconstriction associated with oxidative stress. Because long-term administration of a superoxide scavenger reduces blood pressure and oxidative stress in vivo, this study suggests a role for oxygen radicals in the maintenance of hypertension in SHR.

Administration, Oral↗
PubMed1999

Natriuretic and diuretic actions of a highly selective adenosine A1 receptor antagonist.

The natriuretic and diuretic action of a highly selective adenosine A1 receptor (A1AdoR) antagonist, 1,3-dipropyl-8-[2-(5,6-epoxy)norbornyl]xanthine (CVT-124), was investigated in anesthetized rats. CVT-124 (0.1 to 1 mg/kg) caused dose-dependent increases in urine flow and fractional and absolute sodium excretion of by six- to 10-fold and, at 0.1 mg/kg, increased the GFR (1.6+/-0.1 to 2.5+/-0.2 ml/min; P<0.01). There were no changes in BP or heart rate. CVT-124 reduced absolute proximal reabsorption (26+/-3 to 20+/-2 nl/min; P<0.05) despite unchanged proximally measured, single-nephron GFR (SNGFR) (42+/-5 to 44+/-4 nl/min; NS) and thereby decreased fractional proximal reabsorption (60+/-3 to 46+/-4%; P<0.05). Despite increasing distal tubular fluid flow rate (5.4+/-0.7 to 9.7+/-0.9 nl/min; P<0.001), it reduced the proximal-distal difference in SNGFR (before: 9.4+/-1.0 versus during CVT-124: 4.6+/-1.5 nl/min; P<0.01), suggesting that it had blunted the effects of the macula densa on SNGFR. Direct measurements of maximal tubuloglomerular feedback (TGF) responses were made from proximal stop flow pressure (PSF) during orthograde loop perfusion from the proximal tubule with artificial tubular fluid at 40 nl/min. TGF was blunted by intravenous CVT-124 (0.5 mg/kg; deltaPSF with vehicle: 8.3+/-0.6 versus CVT-124: 6.5+/-0.3 mm Hg; n = 9; P<0.01). In conclusion, A1AdoR blockade reduces proximal reabsorption and uncouples it from glomerular filtration. It increases distal delivery of fluid yet does not activate a macula densa-dependent fall in SNGFR because it blunts the TGF response. Natriuresis accompanied by blockade of proximal glomerulotubular balance and TGF characterizes a new class of diuretic drugs.

Analysis of Variance↗
PubMed1999

Nitric oxide and tubuloglomerular feedback.

Glomerular filtration is closely coupled to tubular reabsorption by a system of tubuloglomerular feedback (TGF). TGF operates within the juxtaglomerular apparatus (JGA) of each nephron, where changes are sensed in the salt content of fluid at the luminal macula densa and that information is transmitted to the glomerular microvasculature to elicit compensatory changes in single nephron glomerular filtration rate (GFR). Type I nitric oxide synthase (NOS) is expressed in the macula densa. Other NOS isoforms may be produced in the mesangium, and glomerular microvessels. These NOSs are strategically positioned to influence each step of the TGF process. However, micropuncture experiments using NOS antagonists have shown that nitric oxide (NO) does not mediate TGF. Instead, local NOS blockade causes the curve that represents TGF to shift leftward and become more steep. Changes in macula densa NO production may underlie the resetting of TGF, which is required in order to keep the TGF curve aligned with ambient tubular flow as tubular flow changes to accommodate physiologic circumstances. Also, macula densa NO production may be substrate limited and dissociated from NOS protein content. The importance of NO to TGF resetting and the substrate dependence of NO production have both been found during changes in dietary salt.

Angiotensin II↗
PubMed1999

Treatment of hypertension in patients with comorbidities: results from the study of hypertensive prescribing practices (SHyPP).

Approximately 50 million people have hypertension. Many agents with differing efficacy, side effects, dosing schedules, and costs are available to treat hypertension. Joint National Committee (JNC) guidelines attempt to simplify this decision by recommending specific agents based on special considerations such as comorbidities. The objective of this study was to survey primary care physicians' antihypertensive prescribing practices and their treatment recommendations for patients with comorbidities. A direct mail survey was sent to a national random sample of 500 office-based primary care internists, family practitioners, and general practitioners. There were no significant differences between initial treatment recommendations at the time of the survey and those recommended before the survey. However, there were several therapeutic classes whose reported utilization for specific comorbidities significantly changed over 18 months. Angiotensin converting enzyme (ACE) inhibitors reportedly increased in patients with congestive heart failure and diabetes. In addition, the reported use of selective beta-blockers increased for patients with a history of myocardial infarction. Physicians did not follow JNC recommendations when initiating treatment in black patients, older patients, or those with mild renal failure. Younger physicians were more likely than older physicians to select agents consistent with guideline recommendations. Physicians did not adhere to JNC guidelines when initiating treatment in patients with comorbidities; however, more physicians are prescribing recommended agents today as compared to 18 months ago. Younger physicians were more likely to prescribe agents consistent with the guidelines. More direct efforts are needed to ensure awareness and compliance with these guidelines.

Adrenergic beta-Antagonists↗
PubMed1999

Metabolic and adverse effects of diuretics.

Diuretics are among the most frequently prescribed drugs. They enjoy a very high clinical reputation for safety and efficacy. However, more than 3 decades of clinical investigation have disclosed a number of abnormalities in fluid electrolyte handling, metabolism, and other adverse effects that can complicate therapy with diuretic drugs. Some of these complications are a direct extension of the wanted action of the drug. These include extracellular fluid volume depletion, associated orthostatic hypotension, and prerenal azotemia. Others are not a direct action of the diuretic, but can be explained as an intranephronal compensation to the diuretic action. These include hypokalemia, in part to increased potassium secretion secondary to the enhanced tubular fluid flow and aldosterone secretion induced by diuretic administration. Metabolic abnormalities are usually mild. Hyperglycemia and carbohydrate intolerance have been related to diuretic-induced hypokalemia, which inhibits insulin secretion by the beta cells, and reductions in extracellular fluid volume and cardiac output. This is compounded by increases in catecholamines from sympathetic nerve activity which decrease peripheral glucose utilization. A mild increase in serum cholesterol concentration is seen frequently during initiation of diuretic therapy, but during steady state therapy after 6 to 12 months, values usually return to baseline. Knowledge of the more common adverse effects induced by diuretics helps the physician in predicting patients at risk and taking effective steps to anticipate or treat adverse responses.

Animals↗
PubMed1998

Structure and transcriptional function of the 5'-flanking region of rat thromboxane receptor gene.

We cloned a cDNA for rat TX receptor, and observed its expression in the kidney, including vascular smooth muscle. The aim of the present study was to clone the 5'-flanking region (5'-FL) of rat TX receptor gene, and to examine its transcriptional gene expression regulation. The 5'-FL was cloned by a PCR method, and the nucleic acid structure of 5'-FL (approximately 1 Kb) was disclosed. The transcription initiation site was shown to be 63 bases upstream of the 5' end of the cDNA by the primer extension. In the 5'-FL, putative AP-1 binding sites, glucocorticoid-responsive elements, NF-kappa B binding sites, GATA box, and shear stress-responsive elements were identified. The 5'-FL was then fused upstream of firefly luciferase cDNA in an expression vector, and we examined its transcriptional activity in transiently transfected cultured vascular smooth muscle cells (VSMC). Luciferase expression was dependent on the length of 5'-FL, and it was significantly stimulated by phorbol 12-myristate 13-acetate (PMA), dexamethasone (Dex), tumor necrosis factor-alpha, and interleukin (IL). By a semi-quantitative RT-PCR method, TX receptor mRNA was shown to be induced by Dex, IL-6, and PMA in cultured VSMC. In conclusion, we have revealed the structure of transcription regulatory region of TX receptor. Expression of TX receptor gene is possibly up-regulated by activation of protein kinase C, glucocorticoid excess, and IL-6, in vascular smooth muscle.

Animals↗
PubMed1998

Divalproate augmentation in lithium-resistant rapid cycling mania in four geriatric patients.

This report describes four geriatric patients, with rapid cycling bipolar disorder, who were treated successfully with divalproex sodium in combination with lithium carbonate, noting that both drugs were necessary for clinical remission of symptoms. Divalproex sodium may actually enhance the sensitivity to lithium carbonate in this population, potentially leading to treatment with lower lithium concentrations. This strategy has an advantage in enabling a greater safety range in the use of lithium carbonate in elderly patients. This report further raises questions as to the nature of rapid cycling illness in the "old-old" population.

Age Factors↗
PubMed1998

Mild metabolic alkalosis impairs the natriuretic response to bumetanide in normal human subjects.

1. This study was designed to test the hypothesis that acid-base status affects the response to a loop diuretic in human subjects. The renal responses to bumetanide (1 mg intravenously) were studied in eight normal subjects consuming a constant diet supplemented for 3 days on three separate occasions with equivalent quantities of NaCl, NaHCO3 (metabolic alkalosis) or NH4Cl (metabolic acidosis). 2. A significant (P < 0.025) reduction in bumetanide-induced diuresis (-40%), natriuresis (-21%), and chloruresis (-25%) was observed during NaHCO3 compared with NaCl. The renal response was unaltered during NH4Cl. 3. The creatinine and para-aminohippurate clearances were unchanged during NaHCO3, as were the blood pressure and plasma levels of renin activity, aldosterone and noradrenaline, and the plasma volume. 4. Bumetanide excretion was increased during NaHCO3 compared with NaCl (2.13 +/- 0.18 versus 1.76 +/- 0.17 micrograms/min, P < 0.025) but was not changed during NH4Cl (1.68 +/- 0.26 micrograms/min; not significant). 5. Plasma aldosterone concentration was increased 3-fold during acidosis and the kaliuretic response to bumetanide was enhanced significantly. 6. In conclusion, compared with NaCl, NaHCO3 reduces the diuretic, natriuretic and chloruretic response to bumetanide without significant changes in renal haemodynamics, plasma volume, the renin-angiotensin-aldosterone axis or the sympathetic nervous system, and despite increasing renal bumetanide excretion. NH4Cl enhances aldosterone secretion and diuretic-induced kaliuresis.

Acidosis↗
PubMed1998

Salt intake determines the renal response to L-arginine infusion in normal human subjects.

Studies in experimental animals have shown that nitric oxide (NO) generation in the kidney from L-arginine participates in adapting renal function to changes in salt intake, but similar studies in human subjects are lacking. Therefore, we compared the infusion of 30 g of L-arginine to 30 g of branched chain amino acids (control), in eight normal human subjects after 5 to 7 days of equilibration to a low salt (LS; 20 mumol.24 hr-1) or high salt (HS; 200 mumol.24 hr-1) intake. Lithium clearance was used as a marker of proximal tubular reabsorption. Compared to the control infusion, L-arginine did not significantly alter blood pressure, inulin or paraaminohippurate clearance, but significantly increased (P < 0.05) the excretion of NO2 + NO3 (NOx) (LS, 157 +/- 46 to 210 +/- 48 mumol.min-1; HS, 138 +/- 30 to 182 +/- 70) and cGMP (LS, 253 +/- 63 to 337 +/- 76 pmol.min-1; HS, 311 +/- 68 to 563 +/- 52). Renal sodium excretion was decreased by L-arginine infusion during the low salt intake (45 +/- 5 to 21 +/- 3 mumol.min-1; P < 0.05) but was increased by L-arginine during the high salt intake (298 +/- 56 to 537 +/- 84 mumol.min-1; P < 0.05). The calculated fractional reabsorption of sodium in the proximal and distal nephrons, as assessed from lithium and sodium clearances, was increased by L-arginine during the low salt intake but was decreased by L-arginine during the high salt intake. L-arginine increased plasma insulin concentration significantly (P < 0.05). This effect was independent of salt intake (LS, 67 +/- 7 to 92 +/- 13 ng.ml-1; HS, 66 +/- 7 to 76 +/- 9 ng.ml-1). L-arginine did not significantly after plasma renin activity. In conclusion, L-arginine increases the excretion of NOx and cGMP and increases plasma insulin, but the effect on sodium excretion depends upon salt intake. L-arginine enhances Na reabsorption in the proximal and distal nephrons during the low salt intake, but inhibits it during the high salt intake. Effects of L-arginine on NO and cGMP may contribute to its effects on Na reabsorption.

Adult↗
PubMed1998

Macula densa nitric oxide synthase: expression, regulation, and function.

The type 1 brain nitric oxide synthase (bNOS) isoform occurs in macula densa (MD) cells where it functions to vasodilate the afferent arteriole and blunt expression of tubuloglomerular feedback (TGF). Dietary salt restriction enhances bNOS expression, yet microperfusion studies with NOS inhibitors imply that it is functionally inactive. We thus assessed the hypothesis that reduced L-arginine (L-Arg) availability during low salt (LS) intake limits MD NO generation. Maximal TGF responses were recorded during Henle's loop perfusion with artificial tubular fluid (ATF). Microperfusion of L-Arg into the MD of LS, but not normal or high-salt (HS) rats blunted maximal TGF responses (8.0 +/- 0.4 to 6.0 +/- 0.5 mm Hg; N = 23; P < 0.01). Response to L-Arg was stereospecific, inhibited by coperfusion with monomethyL-L-arginine (L-NMA), and dependent on system y+ transport, because it was blocked by coperfusion with the competitors L-lysine or L-homoarginine. Absorption of [3H]-L-Arg from the perfused loop, via an L-Arg- or L-homoarginine-inhibitable process, was enhanced during HS. Salt restriction thus diminishes TGF attenuation by NO in the MD despite enhanced bNOS expression because of limited delivery and/or uptake of L-Arg via system y+. This defines a novel mechanism of renal microcirculatory adaptation to salt restriction via L-Arg-dependent changes in TGF.

Animals↗
PubMed1998

Role of macula densa NOS in tubuloglomerular feedback.

Recent studies have amply confirmed the robust expression of neuronal nitric oxide synthase (nNOS) in macula densa cells and its function in blunting tubuloglomerular feedback responses. Regulation of nNOS may occur at many levels: (1) transcriptional and translational regulation, which is enhanced by salt restriction and angiotensin II; (2) functional enhancement by L-arginine delivery and uptake via system Y+, which is enhanced during salt loading; (3) structural activation and feedback inhibition provided by postsynaptic density proteins co-expressed with nNOS in the macula densa; (4) competitive inhibition by dimethylarginines, which can be metabolized via NG, NG dimethylarginine dimethylaminohydrolase co-expressed with nNOS in the macula densa; and (5) intracellular activation linked to changes in [Ca++] or pH during luminal Na+ reabsorption. Nitric oxide, once formed, can be degraded by O2- produced principally in the interstitium between the macula densa and afferent arteriole and in the wall of the arteriole. In genetic hypertension, tubuloglomerular feedback responses are enhanced, in part at least because of diminished buffering by macula densa NO and enhanced O2- generation in the juxtaglomerular apparatus. These recent studies highlight the importance of the macula densa nitric oxide-tubuloglomerular feedback system in adapting glomerular hemodynamics and renal function to changes in salt intake, and define potentially important defects in models of genetic hypertension.

Animals↗