Effects of natriuretic peptide receptor inhibition on remnant kidney function in rats

To identify the contribution of natriuretic peptide (NP) activity to the adaptative increases in glomerular filtration rate (GFR), effective renal plasma flow rate (ERPF) and fractional sodium excretion (FENa) observed in the remnant kidney, we investigated the acute effects of administering HS-142-1 (HS), a potent NP receptor antagonist, in 5/6th nephrectomized (NPX) rats. In addition to normal sodium intake, high or low sodium intakes were used to stimulate or suppress, respectively, endogenous NP activity in NPX rats. In rats three days after NPX on high sodium, HS (20 mg/kg bolus i.v.) reduced GFR from 0.55 +/- 0.05 to 0.35 +/- 0.04 ml/min; ERPF from 1.83 +/- 0.19 to 1.53 +/- 0.16 ml/min; and FENa from 7.1 +/- 1.1 to 1.6 +/- 0.4%, without affecting MAP. Similar changes of lesser magnitude were observed in NPX rats on normal sodium intake. By contrast, GFR, ERPF, FENa and MAP were unchanged following HS in NPX rats on low sodium intake, suggesting that the magnitude of responses to HS is dependent upon the expected levels of activity of NP. We conclude that in anesthetized rats, natriuretic peptides contribute to the compensatory increases in GFR, ERPF and FENa observed in the remnant kidney under normal and salt-replete conditions.     

Impaired expression of atrial natriuretic peptide in diabetic rats with myocardial infarction

We evaluated the effects of myocardial infarction (MI) on the hemodynamics and the expression of atrial natriuretic peptide (ANP) mRNA in rats with streptozotocin-induced diabetes. Eight weeks after streptozotocin injection, the diabetic rats and age-matched nondiabetic controls underwent coronary artery ligation. One week later, the left ventricular end-diastolic pressure, systolic blood pressure, infarct size, and serum ANP levels did not differ significantly between the diabetic and nondiabetic rats. Compared with control animals without MI, the atrial ANP/beta-actin mRNA ratio in rats with MI was increased to 195% in diabetic animals and 213% in nondiabetic animals. In the left ventricle, however, the ANP/beta-actin mRNA ratio in diabetic animals with MI was increased to only 131% compared with control animals, whereas the corresponding increase in nondiabetic animals was 240% (p<0.05). Thus, the modulation of ANP mRNA expression after MI was impaired in the left ventricle, but not in the atria, of diabetic rats. A reduced myocardial expression of ANP could increase the morbidity and mortality associated with cardiovascular disorders in patients with diabetes.     

Upregulation of angiotensin converting enzyme by atrial natriuretic peptide and cyclic GMP in human endothelial cells

OBJECTIVE: To examine the role of atrial natriuretic peptide (ANP) and cyclic GMP in the regulation of angiotensin converting enzyme (ACE) in cultured human endothelial cells. METHODS: Cultured endothelial cells from human umbilical veins (HUVEC) were treated with ANP (0.3-30 nM), 8-Br-cGMP (1-100 microM), Rp-8-Br-PET-cGMPS (1 microM), or the phosphodiesterase inhibitors, zaprinast (10-100 microM), dipyridamole (1-10 microM), or isobutyl methyl xanthine (IBMX, 0.1-0.5 mM). ACE amounts were measured by inhibitor binding assay and cellular cGMP levels by radioimmunoassay. RESULTS: ANP caused a dose dependent increase in ACE measured in intact endothelial cell culture. The stimulatory effect of ANP was blocked by Rp-8-Br-PET-cGMPS, a protein kinase G inhibitor. The cyclic GMP analog, 8-Br-cGMP and the cyclic GMP specific phosphodiesterase inhibitor, zaprinast, both increased ACE. Increase of ACE was also caused by nonspecific phosphodiesterase inhibitors, dipyridamole and IBMX. Intracellular cGMP levels were shown to increase by ANP, and phosphodiesterase inhibitors. CONCLUSIONS: These data suggest that cGMP is an intracellular mediator regulating ACE and that ANP induced increase of ACE is mediated via a cGMP dependent mechanism.     

Inhibitory effect of aldosterone on the natriuretic response to atrial natriuretic peptide in hypocapnic rats

1. Previous studies have shown that acute hypocapnia blunts the natriuretic effect of atrial natriuretic peptide (ANP) independently of the renal nerves and that the effect of ANP is restored by total adrenalectomy. We investigated the natriuretic response to ANP in potassium canrenoate (aldosterone receptor antagonist)-treated rats to clarify whether aldosterone contributes to the attenuated natriuretic response to ANP during hypocapnia. 2. Wistar rats, challenged with either canrenoate or saline vehicle, were infused with 10 micrograms/kg per h ANP during acute hypocapnia achieved by mechanical ventilation. 3. In saline-treated hypocapnic rats, ANP infusion failed to increase the fractional excretion of sodium (FENa) (from 3.49 +/- 0.26 to 5.03 +/- 0.42%, respectively; n = 6) which was similar to values for time control rats (from 3.00 +/- 0.61 to 4.41 +/- 0.68%; n = 6). The hyporesponsiveness to ANP during hypocapnia was also evident when the FENa was compared with that of normocapnic rats (from 3.92 +/- 0.69 to 7.87 +/- 0.45%; P < 0.05; n = 6). In canrenoate-treated rats, ANP infusion caused greater increases in sodium excretion (FENA from 3.05 +/- 0.71 to 7.21 +/- 0.45%; P < 0.05; n = 8) than saline infusion (FENA from 4.16 +/- 1.11 to 5.47 +/- 0.66%; n = 6), despite the hypocapnia. The increase in FENA after ANP infusion during hypocapnia (4.16 +/- 0.86%) was similar to the increase seen during normocapnia (3.89 +/- 0.86%; n = 9). 4. In conclusion: (i) acute hypocapnia blunts the natriuretic effects of ANP; and (ii) this attenuation is restored by potassium canrenoate treatment. The data suggest that aldosterone plays an important role by limiting the renal actions of ANP during acute hypocapnia.     

Brain natriuretic peptide (BNP) gene expression in the heart of vasopressin-deficient Brattleboro rats

This study describes the bacteriological and mycological investigation of 212 ear swab samples of dogs with an otitis externa. 11 samples were sterile. Malassezia pachydermatis could be cultivated in 72.1% of all samples, in 21.9% of these cases in pure culture. In 27.9% of all samples only bacteria were found. Coagulase-positive haemolytic Staphylococcus and Malassezia pachydermatis were isolated together in 31.8% of all ear swab samples. Pseudomonas aeruginosa could be detected in 22.9%, haemolytic Streptococcus in 8.0%. The evaluation of antibiograms showed little resistance of staphylococcus to most common antibiotics or chemotherapeutics respectively, but the growth of Pseudomonas aeruginosa and especially Proteus spec. was only inhibited by a few substances.     

The interaction of atrial natriuretic peptide with other bioregulators of kidney function in chronic glomerulonephritis in children

A study was made of renin-angiotensin-aldosterone system activity and plasmic concentrations of atrial natriuretic peptide (NUP) as well as antidiuretic hormone in children with primary glomerulonephritis. A close relationship was established of these parameters in regulation of water-salt homeostasis. The above systems are involved in pathogenesis of childhood glomerulonephritis. This finding should be considered in development of pathogenetically validated therapy of glomerulonephritis, including introduction of synthetic NUP.     

The rise and fall of atrial natriuretic peptide for acute renal failure

Varices in unusual sites constitute a minor but significant cause of gastrointestinal bleeding in patients with liver disease. We report a case of varices across the anastomotic line between the jejunum and gallbladder after cholecystojejunostomy. Although such varices have been demonstrated by angiography, to our knowledge they have never been demonstrated by small bowel enema (enteroclysis). We report a case and describe the findings on enteroclysis.     

Antagonist for atrial natriuretic peptide receptors ameliorates glomerular hyperfiltration in diabetic rats

To evaluate the possible contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration, we examined the effect of non-peptide competitive antagonist for biological receptors of ANP, HS-142-1, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in diabetic rats. Increased GFR and RPF in diabetic rats were significantly ameliorated by the injection of HS-142-1, while blood pressure remained unchanged. Urinary cyclic GMP excretion was significantly higher in diabetic rats than in control rats and HS-142-1 decreased urinary cGMP excretion significantly. These results indicate that atrial natriuretic peptide contributes to the development of glomerular hyperfiltration and hyperperfusion in diabetes and HS-142-1 might be useful in the treatment of them.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8 pg/ml; ANP: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 +/- 1.8%, ANP 40.2 +/- 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 +/- 1.0 and 60.3 +/- 4.0 pg/ml in patients with normal LVEDP and 31.7 +/- 3.6 and 118.3 +/- 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001) or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term effects of pentobarbital anesthesia on the atrial natriuretic peptide system in rats

The midline fascial splitting approach is a modified midline approach to the iliac crest for bone graft that takes advantage of the anatomic planes between layers of the dorsal lumbar fascia. Two hundred consecutive grafts were taken by this technique with one superficial infection, two cases of serous hematoma, and three patients with significant postoperative pain at the harvest site, for an overall complication rate of 3%. In comparison, bone grafts were harvested from 200 consecutive patients by the midline subcutaneous approach to the iliac crest with 2 deep infections, 1 cluneal nerve injury, 15 patients with severe and disabling pain at the harvest site, and 12 patients with a serous hematoma, for an overall complication rate of 15%. The midline fascial splitting approach significantly reduced the incidence of postoperative serous hematoma (P < 0.007) as well as the incidence of significant and disabling pain (P < 0.001). In addition, the approach is simple, straightforward, anatomic, and decreases trauma to soft tissues.     

Renal natriuretic effects of atrial natriuretic peptide in dogs with alloxan-induced acute pulmonary edema

During a lecture on clinical surgery that he gave at the H?tel-Dieu Hospital in Paris in 1831, Guillaume Dupuytren established the nature of "Permanent retraction of the fingers", that has been designated Dupuytren's contracture since the end of the XIXth century. The nosological individualization of this soft tissue rheumatism is analyzed based on a review of Dupuytren's lectures and of writings by XIXth century practitioners; the other two conditions included in Dupuytren's diathesis, namely Ledderhose's contracture and Peyronie's disease, are also discussed.     

Metoclopramide does not affect renal function and atrial natriuretic peptide release in response to acute saline loading in conscious rats

The medication regimens of 243 children aged 1-16 years were analysed. The children were resident in five Districts in the Northern Region, England and were taking medication orally in liquid or syrup form for chronic disease. 39% of the children were under 5 years of age and 44% were aged 5-11 years, with slightly more males in most age groups. Epilepsy, chronic renal disease and cystic fibrosis were the most common medical problems for which the medicines were prescribed long-term. The duration of medication ranged between 3 months and 12 years; the average duration varied according to the disease and the type of medicine. Most of the anticonvulsants and vitamins had been used for 2 years or more, whereas most of the anti-asthmatic drugs were used for a period of up to a year only. Twenty six (39%) of the 67 different preparations used contained sugar, 19 (28%) were sugar-free, and the sweetening agent in the remainder varied according to how they were prescribed. Specificity of prescribing was the major determinant in the dispensing of either the sugar-containing or the sugar-free medicines.     

SPARC gene expression is reduced in early diabetes-related kidney growth

Renal enlargement is a characteristic feature of diabetes in humans and experimental animals that may predict subsequent renal disease. The biological processes involved in diabetes-related kidney growth are complex and involve changes in extracellular matrix, cell hypertrophy and hyperplasia. Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix protein with anti-adhesive, antiproliferative and matrix remodeling properties. We examined kidney SPARC gene expression and protein content in early experimental diabetes. By Northern blot analysis, kidney SPARC mRNA fell in diabetic animals at day 1 to 40 +/- 15% of controls levels (mean +/- SEM, P < 0.01) to 42% +/- 11% on day 3 (P < 0.01) with a further decrease at day 7 to 29 +/- 7% (P < 0.001). In situ hybridization demonstrated SPARC mRNA within glomeruli renal interstitial cells and in blood vessels but not in tubular epithelial cells. SPARC mRNA was decreased in diabetic rats within a change in the pattern of distribution. By immunofluorescence, SPARC protein was detected in glomeruli and tubular basement membrane. Diabetes was associated with a decrease in SPARC protein at both sites. These data demonstrate that the onset of diabetes-related kidney growth is associated with a reduction in SPARC mRNA and protein. In the context of the known biological actions of SPARC, the findings in the present study implicate this matrix protein in the pathogenesis of diabetes related kidney growth.     

Environmental upregulation of the atrial natriuretic peptide gene in the living fossil, Limulus polyphemus

Northern blot analysis revealed that atrial natriuretic peptide (ANP) gene expression occurs in heart, hematocytes and gills of the invertebrate Limulus polyphemus, the horseshoe crab. In low salinity and on land ANP prohormone messenger RNA in Limulus' heart was 32-fold less compared to that in a vertebrate heart (i.e., rat, Rattus norvegicus). ANP gene expression doubled (P < 0.05) in Limulus' heart and gills with change from land and low salinity to medium salinity and osmolality. ANP gene expression was 10-fold higher in Limulus' gills in seawater (i.e., high salinity). The products of this ANP gene expression (i.e., ANP, long acting natriuretic peptide, vessel dilator and kaliuretic peptide) were released and increased in the circulation, i.e., hemolymph, of Limulus proportional to the increase in salinity and osmolality (P = <0.01). These results suggest that modification of ANP gene expression enables animals to adapt to freshwater, seawater, and land.     

Insertion/deletion polymorphism in the angiotensin-converting enzyme gene is associated with atrial natriuretic peptide activity after exercise

Serotonin 2A receptor (5-HT2A receptor) is widely distributed in the central nervous system, and has been suggested to be involved in a variety of behavioral conditions and neuropsychiatric disorders. Two polyclonal antibodies were raised against the N-terminus peptide of rat 5-HT2A receptor in chickens (5-HT2A-N) and a glutathione S-transferase fusion protein that contained the C-terminus of the mouse 5-HT2A receptor in rabbits (5-HT2A-C). Affinity-purified 5-HT2A-N and -C antibodies reacted strongly with a single band of 77-78 kDa in postsynaptic density proteins prepared from the rat cortex. The distribution pattern of immunoreactive structures in the rat brain was virtually the same for the two antibodies. The highest levels of immunoreactivity were observed in the olfactory bulb, neocortex, claustrum, piriform cortex, mamillary bodies, pontine nuclei, red nucleus and cranial motor nuclei. In the olfactory bulb, mitral cells were intensely labeled. In the neocortex, many immunoreactive neurons were found in layers II-VI. In layer IV of the neocortex, strong neuropil labeling was observed. In a double-labeling study using chicken 5-HT2A-N and rabbit anti-glial fibrillary acidic protein (GFAP) antibody, a considerable number of GFAP positive cells also showed 5-HT2A immunoreactivity. By using an immunoelectron microscopic technique, 5-HT2A receptor immunoreaction was shown to be localized just beneath the postsynaptic membrane thickening of asymmetric synapses.