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Joseph G Verbalis

Publications and source records attributed to Joseph G Verbalis.

At least 19 recordsLinked to original sources
PubMed2006

Use of steroid profiles in determining the cause of adrenal insufficiency.

HYPOTHESIS: A cortisol response to adrenocorticotropin injection is the standard test for diagnosing adrenal insufficiency. Multiple steroid hormones can now be accurately measured by tandem mass spectrometry in a single sample. The study objective was to determine whether a steroid profile, created by simultaneous measurement of 10 steroid hormones by tandem mass spectrometry, would help determine the cause of adrenal insufficiency. DESIGN: A 10-steroid profile was measured by tandem mass spectrometry during the performance of a standard high dose cortrosyn stimulation test. The steroids were measured at baseline, 30, and 60min following synthetic adrenocorticotropin injection. Adrenal insufficiency was defined as a peak cortisol level of less than 20microg/dL. Testing was conducted in the general clinical research center of a university medical center. Normal volunteers, patients suspected of having adrenal insufficiency, and patients with known adrenal insufficiency participated. RESULTS: Our results showed that adrenal insufficiency of any cause was adequately diagnosed using the response of 11-deoxycortisol, dehydroepiandrosterone, or these analytes combined in a two-steroid profile. A three-steroid profile yielded a test with 100% accuracy for discriminating primary adrenal insufficiency from normal status. Primary adrenal insufficiency was well separated from secondary adrenal insufficiency using only a single aldosterone value. 11-Deoxycortisol, dehydroepiandrosterone, and a two-steroid profile each provided fair discrimination between secondary adrenal insufficiency and normal status. CONCLUSIONS: We conclude that stimulated levels of aldosterone, 11-deoxycortisol, dehydroepiandrosterone, and a two- or three-steroid profile provided additional discrimination between states of adrenal sufficiency and insufficiency. It is proposed that a steroid profile measuring cortisol, aldosterone, 11-deoxycortisol, and dehydroepiandrosterone would potentially improve the ability to determine the cause of adrenal insufficiency.

Adrenal Cortex Hormones↗
PubMed2006

Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia.

BACKGROUND: Hyponatremia (serum sodium concentration, <135 mmol per liter) is a predictor of death among patients with chronic heart failure and cirrhosis. At present, therapy for acute and chronic hyponatremia is often ineffective and poorly tolerated. We investigated whether tolvaptan, an orally active vasopressin V(2)-receptor antagonist that promotes aquaresis--excretion of electrolyte-free water--might be of benefit in hyponatremia. METHODS: In two multicenter, randomized, double-blind, placebo-controlled trials, the efficacy of tolvaptan was evaluated in patients with euvolemic or hypervolemic hyponatremia. Patients were randomly assigned to oral placebo (223 patients) or oral tolvaptan (225) at a dose of 15 mg daily. The dose of tolvaptan was increased to 30 mg daily and then to 60 mg daily, if necessary, on the basis of serum sodium concentrations. The two primary end points for all patients were the change in the average daily area under the curve for the serum sodium concentration from baseline to day 4 and the change from baseline to day 30. RESULTS: Serum sodium concentrations increased more in the tolvaptan group than in the placebo group during the first 4 days (P<0.001) and after the full 30 days of therapy (P<0.001). The condition of patients with mild or marked hyponatremia improved (P<0.001 for all comparisons). During the week after discontinuation of tolvaptan on day 30, hyponatremia recurred. Side effects associated with tolvaptan included increased thirst, dry mouth, and increased urination. A planned analysis that combined the two trials showed significant improvement from baseline to day 30 in the tolvaptan group according to scores on the Mental Component of the Medical Outcomes Study 12-item Short-Form General Health Survey. CONCLUSIONS: In patients with euvolemic or hypervolemic hyponatremia, tolvaptan, an oral vasopressin V2-receptor antagonist, was effective in increasing serum sodium concentrations at day 4 and day 30. (ClinicalTrials.gov numbers, NCT00072683 [ClinicalTrials.gov] [SALT-1] and NCT00201994 [ClinicalTrials.gov] [SALT-2].).

Administration, Oral↗
PubMed2006

A reevaluation of the effects of stimulation of the dorsal motor nucleus of the vagus on gastric motility in the rat.

Our primary purpose was to characterize vagal pathways controlling gastric motility by microinjecting l-glutamate into the dorsal motor nucleus of the vagus (DMV) in the rat. An intragastric balloon was used to monitor motility. In 39 out of 43 experiments, microinjection of l-glutamate into different areas of the DMV rostral to calamus scriptorius (CS) resulted in vagally mediated excitatory effects on motility. We observed little evidence for inhibitory effects, even with intravenous atropine or with activation of gastric muscle muscarinic receptors by intravenous bethanechol. Inhibition of nitric oxide synthase with N(omega)-nitro-l-arginine methyl ester (l-NAME) HCl did not augment DMV-evoked excitatory effects on gastric motility. Microinjection of l-glutamate into the DMV caudal to CS produced vagally mediated gastric inhibition that was resistant to l-NAME. l-Glutamate microinjected into the medial subnucleus of the tractus solitarius (mNTS) also produced vagally mediated inhibition of gastric motility. Motility responses evoked from the DMV were always blocked by ipsilateral vagotomy, while responses evoked from the mNTS required bilateral vagotomy to be blocked. Microinjection of oxytocin into the DMV inhibited gastric motility, but the effect was never blocked by ipsilateral vagotomy, suggesting that the effect may have been due to diffusion of oxytocin to the mNTS. Microinjection of substance P and N-methyl-d-aspartate into the DMV also produced inhibitory effects attributable to excitation of nearby mNTS neurons. Our results do not support previous studies indicating parallel vagal excitatory and inhibitory pathways originating in the DMV rostral to CS. Our results do support previous findings of vagal inhibitory pathways originating in the DMV caudal to CS.

Animals↗
PubMed2006

Cost of illness of hyponatremia in the United States.

BACKGROUND: Hyponatremia is a disorder of fluid and electrolyte balance characterized by a relative excess of body water relative to body sodium content. It is the most common electrolyte disorder encountered in clinical medicine and is associated with negative outcomes in many chronic diseases. However, there is limited information in the literature about health care resource use and costs attributable to the effects of the condition. The purpose of this analysis was to estimate the annual cost of illness of hyponatremia in the United States. METHODS: The study utilized a prevalence-based cost of illness framework that incorporated data from publicly available databases, published literature and a consensus panel of expert physicians. Panel members provided information on: classification of hyponatremia patients, treatment settings for hyponatremia (i.e., hospital, emergency room, doctor's office), and health care resource use associated with the diagnosis and treatment of hyponatremia. Low and high prevalence scenarios were estimated and utilized in a spreadsheet-based cost of illness model. Costs were assigned to units of resources and summarized across treatment settings. RESULTS: The prevalence estimate for hyponatremia ranged from 3.2 million to 6.1 million persons in the U.S. on an annual basis. Approximately 1% of patients were classified as having acute and symptomatic hyponatremia, 4% acute and asymptomatic, 15%-20% chronic and symptomatic, and 75-80% chronic and asymptomatic. Of patients treated for hyponatremia, 55%-63% are initially treated as inpatients, 25% are initially treated in the emergency room, and 13%-20% are treated solely in the office setting. The direct costs of treating hyponatremia in the U.S. on an annual basis were estimated to range between $1.6 billion and $3.6 billion. CONCLUSION: Treatment of hyponatremia represents a significant healthcare burden in the U.S. Newer therapies that may reduce the burden of hyponatremia in the inpatient setting could minimize the costs associated with this condition.

Journal Article↗
PubMed2006

Increased renal alpha-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape.

Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the alpha-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of gamma-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076-F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207-217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-beta-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, alpha- and gamma-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and gamma-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, alpha- or gamma-ENaC or increased MAP associated with "escape."

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2006

Control of brain volume during hypoosmolality and hyperosmolality.

Multiple studies over several decades have provided evidence that both electrolytes and organic osmolytes play crucial roles in regulating brain volume, both during increases as well as during decreases in extracellular fluid osmolality. In both situations, rapidly, and however, changes in brain electrolyte contents appear to occur more represent the first line of defense of brain volume during acute perturbations of body fluid tonicity, while organic osmolytes allow adaptation to more chronic perturbations. For both hyperosmolality and hypoosmolality, the rate of development of the disorder is an important determinant of neurological morbidity and mortality, since sufficiently rapid changes in tonicity can exceed the brain's capacity to regulate its volume leading to more severe degrees of brain edema or dehydration. Recovery from both hyper- and hypoosmolality requires reversal of the adaptive processes that enabled regulation of brain volume in response to the initial insult. However, adaptation and recovery are not symmetrical processes. Marked differences occur in the speed with which the brain is able to lose or to reaccumulate different types of solutes after recovery from chronic disturbances of body fluid tonicity. In general, accumulation, or reaccumulation, of organic solutes by brain tissue is a much slower process than volume regulatory losses of such solutes. As with the adaptation process, the rate of recovery is an important determinant of subsequent morbidity and mortality, since rapid corrections of osmolality can also exceed the capacity of the brain to readjust its solute content, and consequently its volume, back to normal levels. Whether or not transient excesses or deficiencies of either electrolytes or specific organic osmolytes in brain intracellular or extracellular fluid contribute to functional disturbances independently of changes in brain volume is an intriguing question that has not been sufficiently evaluated. Also remaining to be answered are questions regarding other physiological, pathophysiological, and pharmacological factors that either impair or enhance volume regulatory processes, and thereby modify the neurological manifestations accompanying disorders of body fluid osmolality in humans. Finally, a complete understanding of the cellular mechanisms underlying adaptation to and deadaptation from acute and chronic perturbations of body osmolality will be essential to design the most enlightened, and therefore appropriate, treatments for these disorders.

Adaptation, Physiological↗
PubMed2006

Whole-body volume regulation and escape from antidiuresis.

Both individual cells and organs regulate their volume in response to sustained hypo-osmolality via solute and water losses. Similar processes occur in the whole body to regulate the volumes of extracellular fluid (ECF) and intravascular spaces toward normal levels. Body water losses occur via the phenomena "escape from antidiuresis"; solute losses occur through the secondary natriuresis induced by water retention. As a result of resistance to arginine vasopressin (AVP) signaling, escape from antidiuresis is caused by downregulation of kidney aquaporin-2 expression despite high AVP plasma levels. Recent data have implicated downregulation of vasopressin V2R as a potential mechanism of resistance, and suggest that this may be a result of decreased intrarenal angiotensin II signaling in combination with increased intrarenal nitric oxide and prostaglandin E2 signaling. The natriuresis that results in volume regulation of the ECF and vascular spaces is the result of intrarenal hemodynamic changes produced by volume expansion, but the degree to which these effects are modulated by aldosterone secretion and the activity of distal sodium cotransporters and channels remains to be elucidated. The clinical implication of these volume-regulatory processes is that the chronic hyponatremic state is one of water retention and solute losses from intracellular fluid and ECF compartments. The degree to which solute losses versus water retention contribute to hyponatremia will vary in association with many factors, including the etiology of the hyponatremia, the rapidity of development of the hyponatremia, the chronicity of the hyponatremia, the volume of daily water loading, and individual variability. Understanding these volume-regulatory processes allows a better understanding of many aspects of the conundrum of patients with "clinical euvolemia" and dilutional hyponatremia from AVP-induced water retention.

Angiotensin II↗
PubMed2006

Disorders of body water homeostasis in critical illness.

Disorders of sodium and water homeostasis are among the most commonly encountered disturbances in the critical care setting, because many disease states cause defects in the complex mechanisms that control the intake and output of water and solute. Because body water is the primary determinant of extracellular fluid osmolality, disorders of body water balance can be categorized into hypoosmolar and hyperosmolar disorders depending on the presence of an excess or a deficiency of body water relative to body solute. Because the main constituent of plasma osmolality is sodium, hypoosmolar and hyperosmolar disease states are generally characterized hy hyponatremia and hypernatremia, respectively. After a brief review of normal water metabolism, this article focuses on the diagnosis and treatment of hyponatremia and hypernatremia in the critical care setting.

Body Water↗
PubMed2006

AVP receptor antagonists as aquaretics: review and assessment of clinical data.

The antidiuretic hormone arginine vasopressin (AVP) is primarily responsible for regulating osmotic and volume homeostasis of body fluids, largely through binding to vasopressin type 1A (V(1A)) and type 2 (V2) receptors. Increased AVP secretion leads to decreased free water excretion with resulting water retention, and can cause dilutional hyponatremia. A new class of medications known as AVP receptor antagonists induces free water diuresis without natriuresis or kaliuresis, an effect termed aquaresis. Numerous clinical trials show AVP antagonists to be effective at increasing free water excretion and serum sodium in patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion or edema-forming states such as congestive heart failure and cirrhosis. This article reviews clinical trial data on the AVP antagonists in late development (lixivaptan, satavaptan, and tolvaptan) and recently approved for marketing (conivaptan).

Antidiuretic Hormone Receptor Antagonists↗
PubMed2005

Hindbrain chemical mediators of reflex-induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine.

The purpose of this study was to activate a vagovagal reflex by using esophageal distension and nicotine and test whether hindbrain nitric oxide and norepinephrine are involved in this reflex function. We used double-labeling immunocytochemical methods to determine whether esophageal distension (and nicotine) activates c-Fos expression in nitrergic and noradrenergic neurons in the nucleus tractus solitarii (NTS). We also studied c-Fos expression in the dorsal motor nucleus of the vagus (DMV) neurons projecting to the periphery. Esophageal distension caused 19.7 +/- 2.3% of the noradrenergic NTS neurons located 0.60 mm rostral to the calamus scriptorius (CS) to be activated but had little effect on c-Fos in DMV neurons. Intravenous administration of nicotine caused 19.7 +/- 4.2% of the noradrenergic NTS neurons 0.90 mm rostral to CS to be activated and, as reported previously, had no effect on c-Fos expression in DMV neurons. To determine whether norepinephrine and nitric oxide were central mediators of esophageal distension-induced decrease in intragastric pressure (balloon recording), N(G)-nitro-L-arginine methyl ester microinjected into the NTS (n = 5), but not into the DMV, blocked the vagovagal reflex. Conversely, alpha2-adrenergic blockers microinjected into the DMV (n = 7), but not into the NTS, blocked the vagovagal reflex. These data, in combination with our earlier pharmacological microinjection data with nicotine, indicate that both esophageal distension and nicotine produce nitric oxide in the NTS, which then activates noradrenergic neurons that terminate on and inhibit DMV neurons.

Animals↗
PubMed2005

Small interfering RNA-mediated functional silencing of vasopressin V2 receptors in the mouse kidney.

The antidiuretic effects of arginine vasopressin (AVP) on the kidney are mediated by V2 subtype AVP receptors (V2R). To investigate the role of regulation of V2R in water and sodium homeostasis, we have developed a method for small interfering RNA (siRNA)-mediated inhibition of V2R expression in vivo. Three 21-nt siRNA sequences were chosen that specifically targeted the mouse V2R but shared no appreciable sequence homology to any other known mouse genes, including the vasopressin V1a and V1b receptors. Additionally, an siRNA sequence that shared no significant matches to any known mammalian gene sequences was chosen for use as a control. Chemically synthesized siRNA was complexed with the liposomal transfection reagent DOTAP. Each mouse (male C57BL/6) received 3.6 nmol (approximately 50 microg) of either the control (nonsilencing) or one of the V2R-targeting siRNAs via intravenous injection. Forty-eight hours after injection membranes were prepared from the inner medulla of the kidneys, and V2R expression was measured by a radioligand binding assay and Western immunoblotting. Treatment with one of the V2R-targeting siRNAs (R2) caused a 39.7 +/- 8.7% reduction in V2R-specific binding compared with the control (n = 11, P < 0.05) and a 37.0 +/- 2.3% reduction in V2R protein expression as measured by Western immunoblotting (n = 4, P < 0.001). Additionally, real-time PCR revealed that R2 siRNA treatment induced a 68.8 +/- 2.2% reduction in V2R mRNA. However, this siRNA treatment did not alter the animals' basal urine concentrating capacity under unstimulated conditions. In subsequent experiments, treatment with R2 siRNA was found to significantly attenuate the antidiuretic effects the V2R-specific AVP agonist 1-desamino-[8-D-arginine]vasopressin (dDAVP). Mice were infused with dDAVP (0.25 ng/h) for 3 days to produce maximal antidiuresis and then were injected with either the R2 siRNA or the nonsilencing control. On day 2 after treatment, urine osmolality was significantly decreased from 3,455 +/- 72 in control animals (n = 12) to 3,155 +/- 129 mosmol/kgH2O in R2 siRNA-treated animals (n = 12) (P < 0.05); similarly, on day 2 24-h urine volume was significantly increased from 0.86 +/- 0.07 ml/day to 1.11 +/- 0.06 ml/day in R2 siRNA-treated animals (P < 0.05). In summary we have demonstrated that RNA interference methodology can be used successfully in vivo to significantly reduce functional expression of the V2R in the mouse kidney.

Animals↗
PubMed2005

Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality.

In vitro studies suggest that endothelin-1 (ET-1) inhibits vasopressin (AVP)-stimulated water permeability in the collecting duct (CD). To evaluate the role of CD-derived ET-1 in regulating renal water metabolism, the ET-1 gene was selectively disrupted in the CD (CD ET-1 KO). During normal water intake, urinary osmolality (Uosm), plasma Na concentration, urine volume, and renal aquaporin-2 (AQP2) levels were unchanged, but plasma AVP concentration was reduced in CD ET-1 KO animals. CD ET-1 KO mice had impaired ability to excrete an acute, but not a chronic, water load, and this was associated with increased CD ET-1 mRNA in control, but not CD ET-1 KO, mice. In response to continuous infusion of 1-desamino-8-D-arginine vasopressin, CD ET-1 KO mice had greater increases in Uosm, V2 and AQP2 mRNA, and phosphorylation of AQP2. CD suspensions from CD ET-1 KO mice had enhanced AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ET-1 KO increases renal sensitivity to the urinary concentrating effects of AVP and suggest that ET-1 functions as a physiological autocrine regulator of AVP action in the CD.

Animals↗
PubMed2005

Sodium status of collapsed marathon runners.

CONTEXT: Recommendations for prevention and treatment of medical emergencies in participants in marathon races center on maintenance of adequate hydration status and administration of fluids. Recently, new recommendations for fluid replacement for marathon runners were promulgated by medical and athletic societies. These new guidelines encourage runners to drink ad libitum between 400 and 800 mL/h as opposed to the previous "as much as possible" advice. OBJECTIVE: To assess the sodium and hydration (plasma osmolality) status of collapsed marathon runners after the promulgation of new hydration guidelines. DESIGN: Plasma sodium and osmolality values of runners who presented to the medical tent at the finish line of the 2003 Boston Marathon were measured. RESULTS: Using reference ranges derived from the general population, of 140 collapsed runners, 35 (25%) were hypernatremic (sodium, >146 mEq/L) and 6 (12%) were hyperosmolar (osmolality, >296 mOsm/kg H(2)O), whereas 9 (6%) were hyponatremic (sodium, <135 mEq/L) and 8 (16%) were hypo-osmolar (osmolality, <280 mOsm/kg H(2)O). Compared with a population of marathon runners who had experienced no medical difficulties, 9% of the runners were hypernatremic, 5% were hyponatremic, 8% were hypo-osmolar, and none were hyperosmolar. CONCLUSIONS: Our findings indicate a significant incidence of hypernatremia with hyperosmolality and hyponatremia with hypo-osmolality among collapsed runners despite the new fluid intake recommendations, suggesting that either further educational measures are required or that the new guidelines are not entirely adequate to prevent abnormalities in fluid balance. Furthermore, the immediate medical management of hypernatremia and hyponatremia is different. Administration of fluids to severely hyponatremic patients may result in fatal cerebral edema. Our findings caution against institution of treatment until laboratory tests determine the patient's sodium status.

Dehydration↗
PubMed2004

Regulation of gene expression in magnocellular neurons in rat supraoptic nucleus during sustained hypoosmolality.

Hypoosmolality produces a dramatic inhibition of vasopressin (VP) and oxytocin gene expression in the supraoptic nucleus (SON). This study examines the effect of sustained hypoosmolality on global gene expression in the oxytocin and VP magnocellular neurons of the hypothalamo-neurohypophysial system, to identify genes associated with the magnocellular neuron's adaptation to this physiological condition. Using laser microdissection of the SON, T7-based linear amplification of its RNA, and a 35,319-element cDNA microarray, we compare gene expression profiles between SONs in normoosmolar (control), 1-desamino-[8-D-arginine]-VP-treated normoosmolar, and hypoosmolar rats. We found 4959 genes with statistically significant differences in expression between normosmolar control and the hypoosmolar SONs, with 1564 of these differing in expression by more than 2-fold. These genes serve a wide variety of functions, and most were up-regulated in gene expression in hypoosmolar compared with control SONs. Of these, 90 were preferentially expressed in the SON, and 44 coded for transcription-related factors, of which 15 genes were down-regulated and 29 genes were up-regulated in the hypoosmolar rat SONs. None of these transcription-related factor genes significantly changed in expression after sustained 1-desamino-[8-D-arginine]-VP-treatment alone, indicating that these changes were associated with the hypoosmolar state and not due solely to a decreased activity in the SON. Quantitative in situ hybridization histochemistry was selectively used to confirm and extend these microarray observations. These results indicate that the hypoosmolar state is accompanied by a global, but selective, increase in expression of a wide variety of regulatory genes in the SON.

Animals↗
PubMed2004

Glucose does not activate nonadrenergic, noncholinergic inhibitory neurons in the rat stomach.

We reported previously that intravenously administered d-glucose acts in the central nervous system to inhibit gastric motility induced by hypoglycemia in anesthetized rats. The purpose of this study was to determine whether this effect is due to inhibition of dorsal motor nucleus of the vagus (DMV) cholinergic motoneurons, which synapse with postganglionic cholinergic neurons, or to excitation of DMV cholinergic neurons, which synapse with postganglionic nonadrenergic, noncholinergic (NANC) neurons, particularly nitrergic neurons. Three approaches were employed: 1) assessment of the efficacy of d-glucose-induced inhibition of gastric motility in hypoglycemic rats with and without inhibition of nitric oxide synthase [10 mg/kg iv nitro-l-arginine methyl ester (l-NAME)], 2) assessment of the efficacy of intravenous bethanechol (30 mug.kg(-1).min(-1)) to stimulate gastric motility in hypoglycemic rats during the time of d-glucose-induced inhibition of gastric motility, and 3) determination of c-Fos expression in DMV neurons after intravenous d-glucose was administered to normoglycemic rats. Results obtained demonstrated that l-NAME treatment had no effect on d-glucose-induced inhibition of gastric motility; there was no reduction in the efficacy of intravenous bethanechol to increase gastric motility, and c-Fos expression was not induced by d-glucose in DMV neurons that project to the stomach. These findings indicate that excitation of DMV cholinergic motoneurons that synapse with postganglionic NANC neurons is not a significant contributing component of d-glucose-induced inhibition of gastric motility.

Animals↗