Concha bullosa in chronic sinusitis.

Sinusitis is an important cause of morbidity and one of the major sources of income loss. Anatomical variations of the nose have been reported to predispose to sinusitis. These variations include concha bullosa, nasal septal deviation and oversized bulla. The aim of this study was to determine the proportion and the distribution of concha bullosa in patients with chronic sinusitis and to determine the relationship between concha bullosa and age, sex, ethnicity. A cross-sectional study was conducted at the Department of Ear, Nose and Throat in Kuala Lumpur Hospital (HKL). Data was collected retrospectively using a pretested proforma. All patients who underwent Sino nasal surgery between January 1999 and December 2000 and whose preoperative CT scans were available were included in the study. The CT scans were reviewed. Analysis was carried out using Statistical Package for Social Sciences. Out of 146 patients who underwent sinonasal surgery between January 1999 and December 2000, 101 (69.2% preoperative CT scans of these patients were available and these were reviewed. The proportion of patients with concha bullosa was 49.5%. The results showed that there was significant relationship between presence of concha bullosa and age and sex. The overall mean age of patient with concha bullosa was 35.7 years (95% CI 12.1-39.3) and ranged from 11-years to 56-years. The mean age of respondents with concha bullosa was significantly lower than patients without concha bullosa 41.98 (95% CI 37.6-46.3; t-test = 2.221; df=99; p < 0.05). Concha bullosa was significantly more in females (66.0%) compared to males (chi2 = 4.465, df=1, p < 0.05). There was no significant relationship between presence of concha bullosa and ethnicity.

Downregulation of endothelin B receptors in cardiomyopathic hamsters.

The mechanisms responsible for abnormal fluid retention in congestive heart failure (CHF) are unclear. Studies were conducted to elucidate how endothelin (ET) may contribute to salt and water retention. Cardiomyopathic (CM) hamsters with moderate heart failure were employed for in vivo and in vitro trials. Clearance methods were used to compare the level of renal function in CM hamsters and control animals. Radioligand binding studies were also performed to determine ET receptor distribution in the inner medullary collecting ducts. CM hamsters exhibited an attenuated response to ANF infusion (FENa: 2.7 +/- 0.5 vs. 5.9 +/- 0.8%, p < 0.01; FEH2O: 1.7 +/- 0.3 vs. 3.2 +/- 0.4%, p < 0.01; UcGMP: 11.2 +/- 2.3 vs. 16.6 +/- 2.0 pmol/min, p < 0.05) and a decrease in total ET receptor density (532 +/- 77 vs. 959 +/- 154 fmol/mg protein, p < 0.005). Particularly ETB receptors were significantly reduced (214 +/- 26 vs. 483 +/- 88 fmol/mg protein, p < 0.003). Enalapril therapy simultaneously restored the natriuretic and diuretic effects of ANF and ET receptor density in the diseased animals. These studies suggest that the renin-angiotensin-aldosterone system and ET hormonal system act together, via ETB receptor downregulation, to promote the abnormal fluid retention observed in CHF.

The cell adhesion molecule DdCAD-1 in Dictyostelium is targeted to the cell surface by a nonclassical transport pathway involving contractile vacuoles.

DdCAD-1 is a 24-kD Ca2+-dependent cell- cell adhesion molecule that is expressed soon after the initiation of development in Dictyostelium cells. DdCAD-1 is present on the cell surface as well as in the cytosol. However, the deduced amino acid sequence of DdCAD-1 lacks a hydrophobic signal peptide or any predicted transmembrane domain, suggesting that it may be presented on the cell surface via a nonclassical transport mechanism. Here we report that DdCAD-1 is transported to the cell surface via contractile vacuoles, which are normally involved in osmoregulation. Immunofluorescence microscopy and subcellular fractionation revealed a preferential association of DdCAD-1 with contractile vacuoles. Proteolytic treatment of isolated contractile vacuoles degraded vacuole-associated calmodulin but not DdCAD-1, demonstrating that DdCAD-1 was present in the lumen. The use of hyperosmotic conditions that suppress contractile vacuole activity led to a dramatic decrease in DdCAD-1 accumulation on the cell surface and the absence of cell cohesiveness. Shifting cells back to a hypotonic condition after hypertonic treatments induced a rapid increase in DdCAD-1-positive contractile vacuoles, followed by the accumulation of DdCAD-1 on the cell membrane. 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole, a specific inhibitor of vacuolar-type H+-ATPase and thus of the activity of contractile vacuoles, also inhibited the accumulation of DdCAD-1 on the cell surface. Furthermore, an in vitro reconstitution system was established, and isolated contractile vacuoles were shown to import soluble DdCAD-1 into their lumen in an ATP-stimulated manner. Taken together, these data provide the first evidence for a nonclassical protein transport mechanism that uses contractile vacuoles to target a soluble cytosolic protein to the cell surface.

Molecular cloning and characterization of DdCAD-1, a Ca2+-dependent cell-cell adhesion molecule, in Dictyostelium discoideum.

Dictyostelium discoideum expresses EDTA-sensitive cell-cell adhesion sites soon after the initiation of development, and a Ca2+-binding protein of Mr 24,000 (designated DdCAD-1) has been implicated in this type of adhesiveness. We have previously purified DdCAD-1 to homogeneity and characterized its cell binding activity (Brar, S. K., and Siu, C.-H. (1993) J. Biol. Chem. 268, 24902-24909). In this report, we describe the cloning of DdCAD-1 cDNAs. DNA sequencing revealed a single open reading frame coding for a polypeptide containing 213 amino acids. The identity of the cDNA was confirmed by amino acid sequences of two cyanogen bromide peptides. The deduced amino acid sequence of DdCAD-1 exhibits a relatively high degree of sequence similarity with members of the cadherin family and protein S of Myxococcus xanthus. Unlike the other cadherins, the carboxyl-terminal region of DdCAD-1 contains a Ca2+-binding motif. Although analyses of the sequence suggest that the polypeptide lacks a signal peptide sequence and a transmembrane domain, immunofluorescence microscopy demonstrates the association of DdCAD-1 with the ecto-surface of the plasma membrane. To investigate the structure/function relationships of DdCAD-1, glutathione S-transferase fusion proteins containing different DdCAD-1 fragments were expressed and assayed for their 45Ca2+ and cell binding activities. These studies revealed that the cell binding activity is dependent on the amino-terminal segment and not the carboxyl-terminal Ca2+-binding domain and showed additional Ca2+-binding site(s) within the amino-terminal segment.

Downregulation of atrial natriuretic factor clearance receptors in experimental chronic renal failure rats.

Studies were performed to examine the changes of renal ANF second messenger guanosine 3',5'-cyclic monophosphate (cGMP) responses and receptor properties in chronic renal failure (CRF). Five-sixths-nephrectomized and sham-operated Wistar rats were used. The glomerular filtration rate was decreased in the five-sixths-nephrectomized rats, which also had significantly higher plasma blood urea nitrogen and plasma atrial natriuretic factor (ANF) levels (148.5 +/- 10.2 vs. 115.7 +/- 7.3 pg/ml, P = 0.01) than the sham rats. In vitro ANF-stimulated cGMP accumulations in glomeruli of five-sixths-nephrectomized rats were higher than controls. Radioligand-binding experiments showed downregulation of the total ANF receptor in both acid and nonacid wash CRF glomeruli (nonacid wash: 189 +/- 25 vs. 362.8 +/- 52.8 fmol/mg protein, P < 0.05; acid wash: 449.8 +/- 67 vs. 652.7 +/- 52.5 fmol/mg protein, P < 0.05). No change in receptor densities was observed in the des(Gln18,Ser19,Gly20,Leu21)atrial natriuretic peptide-(4--23)-NH2-resistant receptors between sham and CRF rat glomeruli. Therefore, downregulation of ANF clearance receptors exists in CRF rat glomeruli, and this is associated with the exaggerated ANF-stimulated cGMP response in these CRF glomeruli. Hypersensitivity of CRF rat to ANF, together with high plasma ANF levels and downregulation of clearance receptor, may contribute to increased sodium excretion in CRF.

In vitro hormone-stimulated atrial natriuretic factor release is increased in experimental renal failure.

The effects of hormone stimulation on atrial natriuretic factor (ANF) release in atria were studied in experimental renal failure rats. In vitro experiments were done in two groups of male Wistar rats. Group 1 rats were sham operated, and group 2 rats were subjected to 5/6 nephrectomy. Overall glomerular filtration rate was significantly reduced (1.98 +/- 0.10 vs. 0.75 +/- 0.05 ml/min, p < 0.001) in nephrectomized rats. These rats were also mildly uremic [blood urea nitrogen (BUN): 18 +/- 0.6 vs. 60 +/- 3.9 mg/dl p < 0.001]. The right atria of partially nephrectomized and sham-operated rats were isolated and perfused in a modified Langendorff apparatus to measure ANF release rate. Experiments were done in two phases. In the initial phase, spontaneous release of ANF was measured. In the second phase, angiotensin II (10(-6) M), vasopressin (10(-6) M) or endothelin (ET 1; 10(-6) M) were added into the perfusate. Spontaneous ANF release by the atria of renal failure rats was significantly elevated compared to intact rats. A significant positive correlation was found between ANF release rate and BUN (r = 0.65, p < 0.01). This suggests that the increase in ANF release by the atria of chronic renal failure (CRF) rats is related to the severity of renal impairment. Angiotensin II, vasopressin and endothelin induced exaggerated increases in ANF release by the atria of CRF rats. These results show that a shift in stimulus response curve is present and can contribute to the observed increase in plasma ANF levels in CRF rats.

Cyclic guanosine monophosphate responses to atrial natriuretic factor, brain natriuretic peptide, but not C-type natriuretic peptide, and the characterization of their receptors in rat medullary thick ascending limb.

The effects of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on renal medullary thick ascending limb (mTAL) have not been fully understood. The aim of this study is to examine the second-messenger responses of rat mTAL to ANF, BNP, and CNP. Characterizations of the ANF, BNP, and CNP receptors in mTAL were also performed by radioligand studies. Results showed that ANF and BNP were both capable of eliciting cyclic guanosine monophosphate (cGMP) responses in mTAL. Conversely, no cGMP response was observed upon stimulation by CNP in mTAL. The presence of ANF receptors was demonstrated by radioligand studies. One receptor site was found, and the Kd and maximum binding capacity were 4.0 +/- 0.45 nmol/L and 277.8 +/- 47.7 fmol/mg protein, respectively. BNP receptors were also found in mTAL, and ANF and BNP were sharing the same receptor. On the contrary, no CNP receptor could be shown by radioligand studies. These results suggest that guanylyl cyclase-coupled receptors (atrial natriuretic peptide receptor-A [ANPR-A]) specific for ANF and BNP are present in rat mTAL, while those for CNP (ANPR-B) are absent. ANF and BNP but not CNP act on mTAL to control water excretion.

Second messenger changes of atrial natriuretic factor and brain natriuretic peptide in kidneys of cardiomyopathic hamsters.

The effects of natriuretic peptides in kidney are blunted in congestive heart failure (CHF). The aim of this study is to examine the changes of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) second messenger productions in CHF. Experiments were conducted on 300-day-old normal and cardiomyopathic hamsters. Blood was collected for ANF measurement. cGMP accumulation studies were done in glomeruli upon ANF and BNP stimulation, and in inner medullary collecting duct (IMCD) cells upon ANF stimulation. Higher plasma ANF levels were found in cardiomyopathic hamsters (811.3 +/- 124.6 vs. 166.6 +/- 13 pg/ml, p < 0.01). ANF-stimulated cGMP accumulations in glomeruli and IMCD cells were higher in cardiomyopathic hamsters. Increased BNP-stimulated cGMP accumulations were also observed in cardiomyopathic hamster glomeruli. These results suggest that the renal hyporesponsiveness to natriuretic peptides in CHF in not due to attenuated ANF and BNP second messenger productions.

Absence of C-type natriuretic peptide receptors in hamster glomeruli.

The distribution of atrial natriuretic peptide receptor B (ANPR-B) varies between tissues and species. The aim of this study is to determine whether ANPR-B is present in the hamster glomeruli. In vitro C-type natriuretic peptide (CNP)- and atrial natriuretic factor (ANF)-stimulated cGMP accumulation studies were performed in hamster glomeruli. Elevated cGMP accumulations were observed upon ANF addition. No cGMP response was seen with CNP. Competitive receptor-binding experiments were performed with 125I-CNP and 125I-ANF against their respective cold peptides in hamster glomeruli. Although no CNP binding was detected, positive ANF binding was found and two types of ANF receptor were demonstrated. The affinity (Kdl) and maximum binding capacity (Bmaxl) of the high-affinity ANF receptor were 0.014 +/- 0.001 nM and 60.4 +/- 10.2 fmol/mg protein, respectively. Those of the low-affinity receptor (Kd2 and Bmax2) were 45.7 +/- 6.2 nM and 28.3 +/- 6.3 pmol/mg protein, respectively. Similarly, saturation binding experiments also failed to show any CNP receptor binding in hamster glomeruli. This finding suggests that ANPR-B is not present in hamster glomeruli and CNP is not a direct physiological regulator of hamster renal function.

Hypersensitivity of inner medullary collecting duct cells to arginine vasopressin and forskolin in cardiomyopathic hamsters.

Circulating arginine vasopressin (AVP) levels are elevated in congestive heart failure (CHF). However, the second messenger changes of the AVP system in CHF have not been explored. The aim of the present study is to determine whether there are changes in cAMP production in the AVP system in CHF. Cardiomyopathic hamsters of strain UM-X7.1 were used. Normal Golden Syrian hamsters were used as controls. IMCD cells were isolated from both group of hamsters. cAMP accumulation experiments were performed with AVP and forskolin stimulation in vitro. There was more cAMP release after stimulation by both AVP and forskolin in the cardiomyopathic than normal hamster IMCD cells. This illustrates that hypersensitivity of IMCD cells to AVP exists in cardiomyopathic hamsters. This may be partly explained by the presence of V2 receptor adenylate cyclase hyperactivity. The hypersensitivity of IMCD cells to AVP may be one of the factors causing fluid retention in CHF.

Mechanism of polyuria after cisplatin therapy.

Cisplatin is an antineoplastic agent. Several nephrotoxic effects are associated with its use including chronic and acute renal failure, renal magnesium wasting, and polyuria. We have investigated polyuria in groups of rats treated with cisplatin at doses of 2.5 and 5 mg/kg body weight given once weekly for 3 weeks to determine possible mechanisms of this impairment. After cisplatin administration, glomerular filtration rate was reduced and significant increases in sodium and water loss were also seen. These changes were associated with decreases in urinary cAMP. Inner medullary collecting duct (IMCD) cells were removed from these animals and were stimulated with graded doses of vasopressin. Cells from cisplatin-treated rats showed an impaired response in cAMP generation to vasopressin stimulation as compared to cells from normal animals. To determine more precisely the site of impairment, the adenylate cyclase complex of the IMCD cells was further studied with forskolin and NaF. Forskolin was used to probe the catalytic unit activating adenylate cyclase, and NaF the guanine nucleotide regulatory protein (G protein). In response to forskolin, cells from cisplatin-treated rats and normal rats responded similarly in generating cAMP. However, following NaF, the cAMP response was blunted in the cells from the cisplatin rats. These results suggested that the catalytic unit was not injured by cisplatin (forskolin study) but the G protein was (NaF). In conclusion, the present study suggests that the polyuria seen following cisplatin administration is associated with an end-organ resistance to vasopressin manifested by reduced cAMP generation, secondary in part or whole to a defect at the level of the G protein.

Effect of pacing on epinephrine-stimulated atrial natriuretic factor release.

Previous in vitro studies showed that epinephrine stimulation can induce atrial natriuretic factor (ANF) release only form the right atrium but not from the left. In addition, sinus node has been shown to play an important role in the release of ANF. In vitro studies were done in isolated left and right rat atria to determine if pacing can induce the left atria to release ANF during epinephrine stimulation. ANF concentrations in the perfusate were measured by a radioimmunoassay method. Epinephrine increased ANF release in the right atria (from 6.3 +/- 0.8 to 10.8 +/- 0.9 pg/min/mg), but not in the unpaced left atria (4.2 +/- 0.4 and 4.2 +/- 0.3 pg/min/mg). However, when the atria were paced, ANF release rose in both the left (from 6.2 +/- 0.5 to 11.5 +/- 1.4 pg/min/mg) and right (from 8.4 +/- 1.15 to 16.6 +/- 1.8 pg/min/mg) atria with epinephrine addition. These results suggest that atrial contraction and tension play an important role in epinephrine-stimulated ANF release.

Atrial natriuretic factor release in cardiomyopathic hamsters.

Studies were done in male cardiomyopathic and normal hamsters to examine the effect of heart failure on atrial natriuretic factor (ANF) secretion. Five groups of animals were studied. The hamsters were 70, 150, 200, 250 and 300 days old. The degree of heart failure became more severe with age. This was associated with a marked increase in left and right atrial weight. Plasma ANF rose in the cardiomyopathic hamsters with age, and no significant change was seen in the normal animals. ANF levels in the atrial tissue declined as the animals developed heart failure, suggesting that ANF release increased in heart failure. To examine these directly, the right and left atria of these animals were isolated and superfused in a modified Langendorff apparatus. The effluents from these experiments were collected and analyzed for ANF levels. Analysis showed that ANF secretion (expressed as pg/min/mg of tissue) declined in heart failure. Since there were significant atrial hypertrophy, the results were also expressed as picogram per minute per atrium. When the data were shown as picogram per minute per atrium, there was a marked increase in ANF secretion. The present data show that one of the factors causing an increase in circulating ANF in heart failure is augmented secretion.

Changes in atrial natriuretic factor processing and secretion with age.

The effect of age on atrial natriuretic factor (ANF) metabolism in the rat was studied. Plasma ANF levels rose with age. A positive correlation was found between age and plasma ANF levels. Molecular forms of ANF were also examined. alpha-ANF and gamma-ANF were present in the circulation. The ratio of gamma-ANF/alpha-ANF increased with age. The atria were isolated and perfused to determine the ANF secretion rate. The spontaneous release of ANF decreased with age. The released ANF mainly consisted of alpha-ANF with a small amount of gamma-ANF. The ratio of gamma-ANF/alpha-ANF in the effluent increased with age. ANF concentrations in the atria varied with age, but the molecular forms did not. gamma-ANF was the main form found in the atria. These results suggest that ANF secretion as well as post-transcriptional processing is altered with age.

Effect of dietary sodium on atrial natriuretic factor released in rats with chronic renal failure.

Studies were done in partially nephrectomized rats to examine the effect of dietary sodium intake on atrial natriuretic factor (ANF) released by the atria. Experiments were done in four groups of male Wistar rats. Group 1 (n = 10) and 3 (m = 10) rats were sham-operated. Group 2 and 4 were 5/6 nephrectomized. Group 1 and 2 were fed a sodium-supplemented diet. Group 3 and 4 received a sodium-deficient diet. Renal functions were similar between group 2 and 4. Plasma ANF level was raised in group 2 (182 +/- 17 pg/ml). Circulating ANF levels in group 1,3 and 4 were 95 +/- 5, 90 +/- 5 and 95 +/- 4 pg/ml, respectively. Atrial ANF contents were higher in partially nephrectomized rats after receiving a sodium-supplemented diet. A reduction in atrial ANF contents occurred when fed a sodium-deficient diet. In vitro studies were done to assess the rate of ANF released. ANF secretory rates were highest in group 2 (11 +/- 1.5 pg/min/mg). There was no difference between group 1,3 and 4. A positive correlation was found between plasma ANF and ANF released in all groups examined. Thus, plasma ANF levels were a good reflection of ANF secretory rates. A significant correlation existed between plasma ANF and sodium excretion in chronic renal failure rats (r = 0.78; p less than 0.01). A dissociation between plasma ANF and water excretion was seen. These results suggest that in chronic renal failure rats, ANF played a role in sodium adaptation.

Effect of dietary magnesium on atrial natriuretic peptide release.

Magnesium is the second most abundant divalent ion in the body, but the effects of this cation on atrial natriuretic peptide (ANP) release have not been examined. The present study was conducted to determine the effect of magnesium on ANP secretion. Experiments were conducted in six groups of male Wistar rats. Each group was assigned a diet containing a different amount of magnesium. Plasma magnesium was 0.42 +/- 0.01, 0.63 +/- 0.01, 0.75 +/- 0.02, 0.97 +/- 0.03, 1.03 +/- 0.01, and 1.19 +/- 0.01 mM in groups I, II, III, IV, V, and VI, respectively. Plasma ANP concentration was significantly higher in the hypermagnesemic animals and significantly lower in the hypomagnesemic rats. A significant positive correlation was found between plasma magnesium and plasma ANP levels (y = 88 + 23 chi; r = 0.46; P less than 0.01). ANP concentration in the atria was lower in hypomagnesemic rats and higher in hypermagnesemic rats. This suggests that the low concentrations of ANP found in the plasma of hypomagnesemic animals were due to the lack of ANP in the atria. The atria from the various groups were isolated and perfused in a modified Langendorff apparatus to measure the rate of ANP secretion. Our results showed that the hypomagnesemic rats have a lower release rate as opposed to that seen in hypermagnesemic animals. A significant correlation was also seen between ANP secretion and tissue ANP concentration. The higher rate of ANP release from the heart of hypermagnesemic animals was due to the presence of more ANP, which was reduced during hypomagnesemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary calcium on atrial natriuretic factor release from isolated rat atria.

Previous studies have shown that acute calcium load causes an increase in circulating plasma atrial natriuretic factor (ANF) levels. The present study was conducted to examine the effect of high dietary calcium on ANF release. Experiments were performed on two groups of male Wistar rats. Hypercalcemic (n = 12) and normocalcemic (n = 12) animals were placed on a high and normal calcium diet, respectively, for 14 days before study. A 24-hour renal clearance was conducted on all animals before superfusion studies. Clearance results showed that high dietary calcium induced a significant increase in plasma calcium (2.69 +/- 0.02 v 2.90 +/- 0.77 mmol/L; P less than .01). This elevation is plasma calcium was associated with a marked increase in calcium excretion (fractional excretion of calcium, 1.91% +/- 0.33% v 8.17% +/- 0.11%, and was correlated with a significant increase in plasma ANF levels (97 +/- 6 v 167 +/- 20 pg/mL). We also measured immunoreactive ANF in the atria of hypercalcemic and normocalcemic rats. ANF content and concentration in the atria were lower in hypercalcemic (465 +/- 36 ng/mg) than in normocalcemic rats (635 +/- 30 ng/mg). This implies that ANF secretion is stimulated by hypercalcemia. To examine this directly, the right atrium from hypercalcemic and normocalcemic rats was superfused in a modified Langendorff preparation. Spontaneous release of ANF from the isolated right atria of hypercalcemic animals (19 +/- 0.8 pg/min/mg) was significantly higher (P less than .01) than from the normocalcemic rats (8.6 +/- 0.3 pg/min/mg). These results suggest that elevation of plasma ANF levels in hypercalcemia is due to an increase in ANF secretion.

The effect of calcitriol on atrial natriuretic factor release from isolated atrium.

Previous studies in our laboratory have shown that patients with idiopathic hypercalciuria (IH) have low basal atrial natriuretic factor (ANF) levels in the plasma. These depressed ANF levels are associated with a high plasma calcitriol levels. In this study, we have evaluated the effect of acute calcitriol administration on ANF release in the isolated atrium. There was a gradual reduction of ANF release as the dosage of calcitriol increased from 1 ng to 10 ng. Beyond 10 ng, additional suppression of ANF release by calcitriol was not observed. These results indicate that acute calcitriol administration causes a significant decrease in ANF release. To further determine whether this reduction in ANF release is due to changes in plasma calcium, additional studies were conducted to examine the effect of acute changes in perfusate calcium on ANF release by isolated atria. Acute elevation of perfusate calcium caused an increase in ANF release, whereas a reduction significantly decreased the secretory rate. These observations suggest that calcitriol affects ANF release by a mechanism not dependent on changes in plasma calcium.

Increased release of atrial natriuretic peptide by the atria of rats with experimental renal failure.

Indirect evidence suggests that atrial natriuretic peptide (ANP) secretion is augmented in chronic renal disease. The object of our present study is to examine the release of ANP from isolated atria obtained from chronic renal failure rats to directly determine whether ANP secretions are increased under these conditions. Experiments were conducted on male Wistar rats (200-225 g) who were subjected to 5/6 nephrectomy of sham operation. Plasma blood urea nitrogen was significantly elevated in 5/6 nephrectomized rats (65 +/- 7 vs. 16 +/- 1 mg%). Overall glomerular filtration rate was 2.36 +/- 0.06 ml/min in sham-operated animals, as opposed to 0.55 +/- 0.11 ml/min in 5/6 nephrectomized rats. Fractional excretion of sodium was significantly higher in 5/6 nephrectomized rats (0.52 +/- 0.01 vs. 1.68 +/- 0.21%). Plasma ANP was 102 +/- 4 pg/ml in normal rats and 161 +/- 14 pg/ml in 5/6 nephrectomized ones. We have also measured immunoreactive ANP in the atria of normal and 5/6 nephrectomized rats. ANP content and concentration in the atria were lower in 5/6 nephrectomized rats. (652 +/- 34 vs. 515 +/- 46 ng/mg of tissue). Right atria from normal and nephrectomized animals was superfused with a modified Langendorff preparation. Spontaneous release of ANP was significantly higher from the nephrectomized rats (17.5 +/- 0.6 pg/min/mg) than from the normal rats (9.8 +/- 0.3 pg/min/mg). These results suggest that ANP may play a role in sodium homeostasis in rats with reduced renal mass.

Single copy sequences in galago DNA resemble a repetitive human retrotransposon-like family.

Galago DNA contains a few single copy sequences that are homologous to the human THE 1 family of repeats. Two of these galago loci have been isolated as genomic clones and their structures are compared to the THE 1 consensus sequence. Whereas the human sequence resembles a proretroviral transposon, the galago sequences provide no evidence for a proretroviral sequence organization. The two galago clones share a common repeat sequence, which is homologous to the U5 region of the THE 1 long terminal repeat. Immediately 3' to this repeat, each galago clone contains sequences that are homologous to mutually exclusive regions of the internal THE 1 sequence. Thus, the human THE 1 sequence can be represented as a mosaic of the two ancestrally related galago loci. The galago loci are transcribed in vivo, so that their conservation in the primate genome could be selected. Human THE 1 repeats apparently resulted by recruiting preexisting cellular sequences via a retrovirally mediated process.