cyclic-gmp and Edema

Topics: Animals; Atrial Natriuretic Factor; Cyclic GMP; Edema; Humans; Kidney; Nephrotic Syndrome; Rats; Sodium

Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (

Topics: Angiotensin I; Animals; Biological Availability; Biomarkers; Blood Pressure; Cardiomyopathy, Dilated; Cyclic GMP; Diet, Sodium-Restricted; Edema; Heart Failure; Kidney; Male; Mice, Inbred C57BL; Natriuretic Peptide, Brain; Nitric Oxide; Nitric Oxide Synthase; Peptide Fragments; Phosphoric Diester Hydrolases; Pleural Effusion; Renin-Angiotensin System; Survival Analysis; Systole

The analgesic and anti-inflammatory properties of Citrus aurantium L. blossoms essential oil (neroli) were investigated in mice and rats. The analgesic activity of neroli was assessed by acetic acid-induced writhing and Eddy's hot plate methods, while acute and chronic anti-inflammatory effects were investigated by inflammatory paw edema in rat and the cotton pellet-induced granuloma tissue model, respectively. Mechanistic studies were conducted using L-nitro arginine methyl ester (L-NAME), an inhibitor of NO synthase. Neroli significantly decreased the number of acetic acid-induced writhes in mice compared to animals that received vehicle only. Also, it exhibited a central analgesic effect, as evidenced by a significant increase in reaction time in the hot plate method. The oil also significantly reduced carrageenan-induced paw edema in rats. The inhibitory activity of neroli (especially at 40 mg/kg) was found to be very close to the standard drug, diclofenac sodium (50 mg/kg). In cotton pellet-induced granuloma, neroli was effective regarding the transudate and granuloma formation amount. Neroli was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) and twenty-three constituents, representing 91.0 % of the oil, were identified. The major components of neroli were characterized as linalool (28.5 %), linalyl acetate (19.6 %), nerolidol (9.1 %), E,E-farnesol (9.1 %), α-terpineol (4.9 %), and limonene (4.6 %), which might be responsible for these observed activities. The results suggest that neroli possesses biologically active constituent(s) that have significant activity against acute and especially chronic inflammation, and have central and peripheral antinociceptive effects which support the ethnomedicinal claims of the use of the plant in the management of pain and inflammation.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Citrus; Cyclic GMP; Drug Evaluation, Preclinical; Edema; Flowers; Gas Chromatography-Mass Spectrometry; Male; Mice; Nitric Oxide; Oils, Volatile; Plant Extracts; Plant Oils; Rats, Wistar; Second Messenger Systems

Pimaradienoic acid (1) is a pimarane diterpene (ent-pimara-8(14),15-dien-19-oic acid) extracted at high amounts from various plants including Vigueira arenaria Baker. Compound 1 inhibited carrageenan-induced paw edema and acetic acid-induced abdominal writhing, which are its only known anti-inflammatory activities. Therefore, it is important to further investigate the analgesic effects of 1. Oral administration of 1 (1, 3, and 10 mg/kg) inhibited the acetic acid-induced writhing. This was also observed at 10 mg/kg via sc and ip routes. Both phases of the formalin- and complete Freund's adjuvant (CFA)-induced paw flinch and time spent licking the paw were inhibited by 1. Compound 1 inhibited carrageenan-, CFA-, and PGE2-induced mechanical hyperalgesia. Treatment with 1 inhibited carrageenan-induced production of TNF-α, IL-1β, IL-33, and IL-10 and nuclear factor κB activation. Pharmacological inhibitors also demonstrated that the analgesic effects of 1 depend on activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway. Compound 1 did not alter plasma levels of AST, ALT, or myeloperoxidase activity in the stomach. These results demonstrate that 1 causes analgesic effects associated with the inhibition of NF-κB activation, reduction of cytokine production, and activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway.

Topics: Acetic Acid; Analgesics; Anti-Inflammatory Agents; Carrageenan; Cyclic GMP; Diterpenes; Edema; Freund's Adjuvant; Hyperalgesia; Interleukin-10; Interleukin-1beta; KATP Channels; Molecular Structure; Pain; Potassium Channels; Signal Transduction; Tumor Necrosis Factor-alpha

Administration of L-nil, a selective inhibitor of inducible nitric oxide synthase (iNOS), improves ileus in an animal model of resuscitation induced intestinal edema. The purpose of this study was to elucidate the iNOS/nitric oxide (NO) signal transduction pathway in intestinal edema.. Male Sprague Dawley rats were divided into two groups; CONTROL and RESUS+VH (edema, 80 cc/kg normal saline (resuscitation) with mesenteric venous hypertension). iNOS mRNA and protein, iNOS activity, NO tissue levels, soluble guanylyl cyclase (sGC) expression, and cyclic guanosine monophosphate (cGMP) levels were measured. As a functional endpoint, we evaluated intestinal contractile strength and frequency in L-nil treated animals.. Edema was associated with increased iNOS mRNA and protein expression without subsequent increases in iNOS activity or tissue NO levels. There was no significant change in sGC expression or increase in cGMP induced by edema. Administration of L-nil did not decrease edema development or preserve contractile strength, but increased contractile frequency.. Hydrostatic intestinal edema is not associated with increased iNOS activity or tissue NO levels. Administration of L-nil in edema increases intestinal contractile frequency. This may represent a potential mechanism for the amelioration of ileus seen with the administration of L-nil.

Topics: Animals; Cyclic GMP; Edema; Gastrointestinal Motility; Guanylate Cyclase; Hydrostatic Pressure; Immunohistochemistry; Intestinal Diseases; Lysine; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction

Many neuromuscular conditions are characterized by an exaggerated exercise-induced fatigue response that is disproportionate to activity level. This fatigue is not necessarily correlated with greater central or peripheral fatigue in patients, and some patients experience severe fatigue without any demonstrable somatic disease. Except in myopathies that are due to specific metabolic defects, the mechanism underlying this type of fatigue remains unknown. With no treatment available, this form of inactivity is a major determinant of disability. Here we show, using mouse models, that this exaggerated fatigue response is distinct from a loss in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase (nNOS) in skeletal muscle is required to maintain activity after mild exercise. We show that nNOS-null mice do not have muscle pathology and have no loss of muscle-specific force after exercise but do display this exaggerated fatigue response to mild exercise. In mouse models of nNOS mislocalization from the sarcolemma, prolonged inactivity was only relieved by pharmacologically enhancing the cGMP signal that results from muscle nNOS activation during the nitric oxide signalling response to mild exercise. Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction-induced signalling from sarcolemma-localized nNOS, which decreases cGMP-mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise-induced signalling.

Topics: Animals; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Disease Models, Animal; Edema; Enzyme Activation; Exercise; Fatigue; Hemodynamics; Humans; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Muscle, Skeletal; Muscular Diseases; Nitric Oxide; Nitric Oxide Synthase Type I; Phosphodiesterase 5 Inhibitors; Protein Transport; Sarcolemma; Signal Transduction

The lymphatic vascular system regulates tissue fluid homeostasis and the afferent phase of the immune response, and it is also involved in tumor metastasis. There is increasing evidence that lymphatic vessels also mediate acute and chronic inflammation. However, the mechanisms and functional consequences of lymphangiogenesis under inflammatory conditions are largely unknown. Here, we show that lymphatic endothelial cells (LECs) specifically express the alpha1beta1 isoform of soluble guanylate cyclase (sGC), that vascular endothelial growth factor-A potently induces sGCalpha1beta1, and that nitric oxide (NO) -induced LEC proliferation, migration, and cGMP production in LECs are specifically dependent on sGCalpha1beta1. Moreover, the specific sGC inhibitor NS-2028 completely prevents ultraviolet B-irradiation-induced lymphatic vessel enlargement, edema formation, and skin inflammation in vivo. These findings identify a crucial role of the NO/sGCalpha1beta1/cGMP pathway in modulating lymphatic vessel function. The blockade of sGCalpha1beta1 signaling might serve as a novel therapeutic strategy for inhibiting lymphangiogenesis and inflammation, in addition to its effects on the blood vasculature.

Topics: Cell Movement; Cell Proliferation; Cells, Cultured; Cyclic GMP; Edema; Enzyme Inhibitors; Gene Expression Regulation, Enzymologic; Guanylate Cyclase; Humans; Immunity, Cellular; Inflammation; Lymphatic Vessels; Nitric Oxide; Nitric Oxide Synthase Type III; Oxadiazoles; Oxazines; Receptors, Cytoplasmic and Nuclear; S-Nitroso-N-Acetylpenicillamine; Soluble Guanylyl Cyclase

Morphine can inhibit inflammatory edema in experimental animals. The mechanisms and sites by which opioids exert this effect are still under debate. Since the spinal level is a site for modulation of the neurogenic component of inflammation, we investigated the effect of intrathecal (i.t.) administration of morphine, and the involvement of spinal nitric oxide (NO)/cyclic-guanosine monophosphate-GMP pathway in carrageenan (CG)-induced paw edema.. Male Wistar rats received i.t. injections of drugs (20 microL) 30 min before paw stimulation with CG (150 microg). Edema was measured as paw volume increase (mL), and neutrophil migration was evaluated indirectly by myeloperoxidase (MPO) assay.. Morphine (37, 75, and 150 nmol) inhibited inflammatory edema, but had no effect on MPO activity. Coinjection with naloxone (64 nmol) reversed the effect of morphine. The corticosteroid synthesis inhibitor, aminoglutethimide (50 mg/kg, v.o.), administered 90 min before morphine injection did not modify its antiedematogenic effect. Low doses of the NO synthase inhibitor, N(omega)-nitro-L-arginine (L-NNA; 10 and 30 pmol) increased, while higher doses (3 and 30 nmol) inhibited edema. The guanylate cyclase inhibitor 1H-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 21 and 42 nmol) increased, while the phosphodiesterase type 5 inhibitor sildenafil (0.15 and 1.5 nmol) inhibited paw edema. Coadministration of a subeffective dose of L-NNA (3 pmol) or ODQ (10 nmol) with morphine prevented its antiedematogenic effect, but sildenafil (0.15 nmol) rendered a subeffective dose of morphine effective (18 nmol). ODQ also prevented the antiedematogenic effect of the NO donor S-nitroso-N-acetyl-penicilamine.. These results support the idea that morphine can act on opioid receptors at the spinal level to produce antiedematogenic, and that the NO/cGMP pathway seems to be an important mediator in this effect.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cyclic GMP; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Enzyme Inhibitors; Guanylate Cyclase; Inflammation; Injections, Spinal; Male; Morphine; Naloxone; Narcotic Antagonists; Neutrophil Infiltration; Neutrophils; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitroarginine; Oxadiazoles; Peroxidase; Phosphodiesterase Inhibitors; Piperazines; Purines; Quinoxalines; Rats; Rats, Wistar; S-Nitroso-N-Acetylpenicillamine; Signal Transduction; Sildenafil Citrate; Spinal Cord; Sulfones; Time Factors

Nitric oxide (NO) plays a central role in the pathogenesis of septic shock. However, the role of the NO produced by endothelial NO synthase (eNOS) in septic shock is still unclear. We examined the effect of chronic eNOS overexpression and the role of eNOS-derived NO in lipopolysaccharide (LPS)-induced septic shock using eNOS transgenic (Tg) mice.. LPS was intraperitoneally injected into Tg and control mice. No differences existed in the peak plasma nitrate and nitrate levels induced by LPS between the 2 genotypes. In LPS-treated control mice, blood pressure progressively declined and reached 60% of basal levels (from 97+/-3 to 59+/-3 mm Hg) 24 hours after LPS injection. In contrast, the blood pressure of LPS-treated Tg mice fell only 15% from basal levels (from 84+/-4 to 71+/-4 mm Hg) after the first 6 hours and, thereafter, it remained at this level. LPS-induced increases in the expression of the mRNA of both vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 in the lungs were significantly lower in Tg mice than in control mice. LPS-induced pulmonary leukocyte infiltration and increases in lung water content were also significantly attenuated in Tg mice. Histological examination revealed that lung injury after LPS injection was milder in Tg mice. Furthermore, Tg mice exhibited enhanced survival from LPS-induced septic shock compared with control mice.. Chronic eNOS overexpression in the endothelium of mice resulted in resistance to LPS-induced hypotension, lung injury, and death. These effects are associated with the reduced vascular reactivity to NO and the reduced anti-inflammatory effects of NO.

Topics: Animals; Aorta; Blood Pressure; Cyclic GMP; Edema; Female; Granulocytes; Hypotension; Immunity, Innate; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Multiple Organ Failure; Nitrates; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitrites; Organ Size; Peroxidase; Shock, Septic; Vasodilation

The antinociceptive effect of Crotalus durissus terrificus venom was investigated in a model of inflammatory hyperalgesia induced by carrageenin. The rat paw pressure test was applied before and 3 h after the intraplantar (i.pl.) injection of carrageenin. The venom administered per os before and 1 or 2 h after carrageenin blocked hyperalgesia. When carrageenin was injected in both hind paws and naloxone into one hind paw, antinociception was abolished only in the paw injected with naloxone. D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP) and nor-binaltorphimine, antagonists of micro- and kappa-opioid receptors, respectively, did not alter the effect of the venom. N,N-diallyl-Tyr-Aib-Aib-Phe-Leu (ICI 174,864), an antagonist of delta-opioid receptors, antagonised this effect. Prolonged administration of the venom did not induce tolerance to this antinociceptive effect. N(G)-methyl-L-arginine (L-NMMA) and methylene blue, inhibitors of nitric oxide synthase and soluble guanylate cyclase, respectively, injected i.pl., antagonised antinociception. These data indicate that both delta-opioid receptors and nitric oxide participate in the mediation of the peripheral antinociceptive effect of C. durissus terrificus venom.

Topics: Analgesics, Non-Narcotic; Animals; Arginine; Carrageenan; Crotalid Venoms; Cyclic GMP; Edema; Enzyme Inhibitors; Hyperalgesia; Male; Methylene Blue; Motor Activity; Narcotic Antagonists; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Rats; Rats, Wistar; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu

Cardiotrophin-1 (CT-1) is a recently discovered member of the gp130 cytokine family, which includes IL-6, IL-11, leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Recent evidence suggests that, like other members of this family, CT-1 may possess anti-inflammatory properties. We hypothesized that in vivo CT-1 administration would attenuate endotoxin (ETX)-induced acute lung injury. We studied the effects of CT-1 (100 microgram/kg ip, 10 min prior to ETX) in a rat model of ETX-induced acute lung injury (Salmonella typhimurium lipopolysaccharide, 20 mg/kg ip). Six hours after ETX, lungs were harvested for determination of neutrophil accumulation (myeloperoxidase, MPO, assay) and lung edema (wet-to-dry weight ratio). Mechanisms of pulmonary vasorelaxation were examined in isolated pulmonary artery rings at 6 h by interrogating endothelium-dependent (response to acetylcholine) and endothelium-independent (response to sodium nitroprusside) relaxation following alpha-adrenergic (phenylephrine)-stimulated preconstriction. CT-1 abrogated the endotoxin-induced lung neutrophil accumulation: 2.3 +/- 0.2 units MPO/g wet lung (gwl) vs 6. 3 +/- 0.3 units MPO/gwl in the ETX group (P < 0.05 vs ETX, P > 0.05 vs control). Similarly, CT-1 prevented ETX-induced lung edema: wet-to-dry-weight ratio, 4.473 +/- 0.039 vs 4.747 +/- 0.039 in the ETX group (P < 0.05 vs ETX, P > 0.05 vs control). Endotoxin caused significant impairment of both endothelium-dependent and -independent pulmonary vasorelaxation, and CT-1 attenuated this injury. Thus, cardiotrophin-1 possesses significant anti-inflammatory properties in a model of endotoxin-induced acute lung injury.

Topics: Acute Disease; Animals; Cyclic GMP; Cytokines; Edema; Endotoxemia; Endotoxins; Lung; Lung Diseases; Male; Neutrophils; Pulmonary Circulation; Rats; Rats, Sprague-Dawley; Vasodilation

Exogenous nitric oxide reduces ischemia-reperfusion injury after solid organ transplantation. Tetrahydrobiopterin, an essential cofactor for nitric oxide synthases, may restore impaired endothelium-dependent nitric oxide synthesis. We evaluated whether tetrahydrobiopterin administration to the recipient attenuates lung reperfusion injury after transplantation in swine.. Unilateral left lung transplantation was performed in 15 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.5 L cold (1 degrees C) low-potassium-dextran solution and preserved for 20 hours. Group I animals served as controls. Group II and III animals were treated with a bolus of tetrahydrobiopterin (20 mg/kg). In addition, in group III a continuous infusion of tetrahydrobiopterin (10 mg/kg per hour over 5 hours) was given. One hour after reperfusion, the recipient right lung was occluded. Cyclic guanosine monophosphate levels were measured in the pulmonary venous and central venous blood. Extravascular lung water index, hemodynamic variables, lipid peroxidation, and neutrophil migration to the allograft were assessed.. In group III a significant reduction of extravascular lung water was noted in comparison with the controls (P =.0047). Lipid peroxidation in lung allograft tissue was significantly reduced in group II (P =.0021) and group III ( P =. 0077) in comparison with group I. Pulmonary venous levels of cyclic guanosine monophosphate increased up to 23 +/- 1 pmol/mL at 5 hours in group II and up to 40 +/- 1 pmol/mL in group III (group I, 4.1 +/- 0.5 pmol/mL [I vs III]; P <.001), whereas central venous levels of cyclic guanosine monophosphate were unchanged in all groups.. Tetrahydrobiopterin administration during lung allograft reperfusion may reduce posttransplantation lung edema and oxygen-derived free radical injury in the graft. This effect is mediated by local enhancement of the nitric oxide/cyclic guanosine monophosphate pathway.

Topics: Animals; Antioxidants; Biopterins; Cryopreservation; Cyclic GMP; Dextrans; Disease Models, Animal; Edema; Endothelium, Vascular; Extravascular Lung Water; Free Radical Scavengers; Hemodynamics; Infusions, Intravenous; Injections, Intravenous; Lipid Peroxidation; Lung Diseases; Lung Transplantation; Neutrophil Infiltration; Nitric Oxide; Nitric Oxide Synthase; Plasma Substitutes; Potassium; Pulmonary Veins; Reactive Oxygen Species; Reperfusion Injury; Swine

1. Intraplantar injection of carrageenan (150 microl, 1-3% w/v) in the rat resulted in a dose-related increase in hindpaw weight (oedema) characterized by a rapid 'early' phase (up to 2.5 h) response followed by a more sustained 'late' phase (2-6 h) response. No change in weight of either the contralateral (i.e. noninjected) hindpaw or hindpaws injected with saline was observed. 2. Six hours after intraplantar injection of carrageenan (1-3% w/v) hindpaw constitutive (i.e. calcium-dependent) nitric oxide synthase (cNOS) activity (determined ex vivo as the conversion of radiolabelled L-arginine to radiolabelled citrulline) was increased (e.g. 2% w/v; 0.64+/-0.08 pmol citrulline mg(-1) protein 15 min(-1) c.f. 0.08+/-0.04 pmol citrulline mg(-1) protein 15 min(-1) in saline-injected, control animals, n=4, P<0.05). Carrageenan injection also resulted in the appearance in hindpaw homogenates of inducible (i.e. calcium-independent) nitric oxide synthase (iNOS, e.g. 2% w/v; 0.67+/-0.14 pmol citrulline mg(-1) protein 15 min(-1), n=4). Hindpaw cyclic GMP concentration was also significantly increased 6 h after intraplantar injection of carrageenan (e.g. 2% w/v; 379.6+/-26.8 fmol mg(-1) protein c.f. 261.8+/-42.2 fmol mg(-1) protein, in saline-injected, control animals, n=4, P<0.05). 3. Pretreatment (5-25 mg kg(-1), i.p., 30 min before carrageenan, 2% w/v) of animals with L-N(G) nitro arginine methyl ester (L-NAME; isoform nonselective inhibitor of NOS) or 7-nitro indazole (7-NI; inhibitor of neuronal NOS, nNOS) caused dose-related inhibition of both the early (2 h) and late (6 h) phase hindpaw oedema, associated with reduced hindpaw iNOS and cNOS activity and cyclic GMP concentration in animals killed at 6 h. Administration of 7-NI (5-25 mg kg(-1), i.p.) to animals 2.5 h after intraplantar carrageenan (2% w/v) injection (i.e. at the end of the early phase oedema response) produced dose-related inhibition of the late phase response. 4. Pretreatment (5-25 mg kg(-1), i.p., 30 min before carrageenan, 2% w/v) of animals with L-N6-iminoethyllysine (L-NIL, selective inhibitor of iNOS) (5-25 mg kg(-1)) failed to affect the early phase hindpaw oedema response but did produce a dose-related inhibition of the late phase oedema. L-NIL pretreatment also inhibited the carrageenan-induced increase in both hindpaw iNOS and cNOS activity as well as the rise in hindpaw cyclic GMP concentration. 5. The present experiments demonstrate an anti-inflammatory effect of 7-NI as evidenced by

Topics: Animals; Carrageenan; Cyclic GMP; Edema; Enzyme Inhibitors; Hindlimb; Indazoles; Lysine; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Rats; Rats, Wistar

Sodium-retaining cirrhotic and chronic caval dogs with ascites show a heterogeneous natriuretic response to atrial natriuretic factor (ANF) infusions such that half will increase their urinary excretion of sodium and half will show no natriuretic response whatsoever. In these studies we have examined several physiological variables that might discriminate between these two experimental populations. We studied 22 caval dogs (11 natriuretic responders, 11 nonresponders) and 19 cirrhotic dogs (9 responders, 10 nonresponders). After an infusion of rat ANP-(1-28), 125 ng.kg-1.min-1, differences in glomerular filtration rate, blood pressure, or urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP) could not differentiate between the two types of dogs. When the left kidney of nonresponding dogs in both the caval and cirrhotic groups was either denervated or vasodilated with acetylcholine bromide (60-80 micrograms/min), the attenuation of the natriuretic response to ANF was not reversed. Papillary plasma flow (PPF) after ANF infusion was measured by a Lillienfield technique and averaged 36 +/- 4 ml.min-1.100 g-1 in normal dogs, 10.7 +/- 0.7 ml.min-1.100 g-1 in both responding and nonresponding caval dogs, and 48.3 +/- 1.1 ml.min-1.100 g-1 for each group of cirrhotic dogs. We conclude that differences in renal perfusion, PPF, cGMP generation, or the presence of intact renal nerves cannot explain the lack of a post-ANF natriuretic response in half of caval or cirrhotic dogs. Other physiological determinants must explain the heterogeneity of natriuretic response to ANF observed in edematous dogs.

Topics: Animals; Ascites; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Denervation; Dogs; Drug Resistance; Edema; Female; Fibrosis; Kidney; Ligation; Male; Natriuresis; Renal Circulation; Sodium; Vasodilation; Vena Cava, Inferior

Topics: Animals; Cyclic AMP; Cyclic GMP; Edema; Foot; Hindlimb; Male; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats