Biomedical subjects

I Hayashi

Publications and source records attributed to I Hayashi.

At least 55 records · Page 3Linked to original sources

PubMed2000

Cyclo-oxygenase-2 enhances basic fibroblast growth factor-induced angiogenesis through induction of vascular endothelial growth factor in rat sponge implants.

Angiogenesis is reportedly enhanced by prostaglandins (PGs). In the present study, we investigated whether or not cyclo-oxygenase (COX)-2 mediated angiogenesis in chronic and proliferate granuloma. In rat sponge implants, angiogenesis was gradually developed over a 14-day experimental period as granuloma formed. This angiogenesis was enhanced by topical injections of human recombinant basic fibroblast growth factor (bFGF). In sponge granuloma, mRNA of COX-1 was constitutively expressed, whereas that of COX-2 was increased with neovascularization in parallel with that of vascular endothelial growth factor (VEGF). Topical injections of bFGF increased the expression of COX-2 mRNA. bFGF-stimulated angiogenesis was inhibited by indomethacin or selective COX-2 inhibitors, NS-398, nimesulide, and JTE-522. The levels of PGE(2) and 6-keto-PGF(1alpha) in the sponge granuloma were increased with bFGF 13 fold and 9 fold, respectively, and these levels were markedly reduced by NS-398. The expression of VEGF mRNA in the granuloma was also enhanced by bFGF, and was reduced by NS-398. Topical injections of PGE(2) and beraprost sodium, a PGI(2) analogue, increased the expression of VEGF mRNA, with angiogenesis enhancement. The enhanced angiogenesis by bFGF was significantly inhibited by topical injections of VEGF anti-sense oligonucleotide. These results suggested that COX-2 may enhance bFGF-induced neovascularization in sponge granuloma by PG-mediated expression of VEGF, and that a COX-2 inhibitor would facilitate the management of conditions involving angiogenesis.

Animals↗

PubMed2000

In vivo transfer of antisense oligonucleotide against urinary kininase blunts deoxycorticosterone acetate-salt hypertension in rats.

We have previously reported that the renal kallikrein-kinin system suppressed the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Kinins were degraded in the kidney mainly by carboxypeptidase Y (CPY)-like kininase. Blockade of renal kinin degradation may reduce hypertension in the developmental stage. We constructed an antisense oligonucleotide against rat CPY homologue (5'-CAT-CTC-TGC-TTC-CTT-GTG-TC-3', AS) and its randomized control oligonucleotide (5'-TCC-TTC-CTG-CTT-GAG-TTC-CT-3', RC), and prepared an HVJ-liposome complex that prolongs and increases the effectiveness of the antisense oligonucleotide. Antisense oligonucleotide was transfected (25 nmole rat(-1), in terms of nucleotide) into the kidney from the renal artery. Blood pressure was measured through a catheter inserted into the abdominal aorta. Mean blood pressure (MBP) in DOCA-salt treated (for 2 weeks) Sprague Dawley strain rats was 130+/-3 mmHg (n=11), and was reduced significantly (P<0.05) more by AS transfection (122+/-4 mmHg, n=6) than by RC treatment (137+/-6 mmHg, n=5) 4 days after the transfection. This reduction in MBP was accompanied by increased urinary sodium excretion (AS, 8.4+/-1.5 mmole day(-1); RC, 4.6+/-0.5 mmole day(-1), P<0.05) and a reduction in urinary CPY-like kininase activity. Ebelactone B (5 mg kg(-1), twice a day, p.o.), an inhibitor for urinary CPY-like kininase, also reduced MBP and induced natriuresis to the same degree as AS. Lisinopril, an inhibitor for angiotensin converting enzyme (ACE) failed to reduce the elevated MBP. These results suggest that CPY-like kininase may have more contribution than ACE to degrade kinin in the kidney, and that knockdown of CPY-like kininase in the kidney may partly prevent rat DOCA-salt hypertension.

Animals↗

PubMed2000

Clonal structure in a dwarf bamboo (Sasa senanensis) population inferred from amplified fragment length polymorphism (AFLP) fingerprints.

Amplified fragment length polymorphism (AFLP) fingerprints were used to reveal clonal structure of a dense population of dwarf bamboo, Sasa senanensis, in a 10-ha study plot at Sugadaira Montane Research Center, University of Tsukuba, Nagano, Japan. We generated AFLP fingerprints for 51 leaf samples, collected at 50 m intervals, using three selective primer pairs. A total of 135-166 fragments were detected per sample, and 22 different fingerprints were identified based on 24-83 differing fragments. Our results demonstrate that the S. senanensis population in our plot consists of at least 22 clones and that the largest single clone occurs over a distance of about 300 m. Furthermore, the clone distribution pattern implies a relationship between site quality and clonal structure.

Clone Cells↗

PubMed2000

Quantitative trait loci for lipid metabolism in the study of OLETF x (OLETF x Fischer 344) backcross rats.

1. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a model of type II diabetes with accompanying dyslipidaemia and obesity. 2. To define chromosomal intervals associated with obesity (abdominal fat weight and plasma leptin levels), dyslipidaemia (plasma triglyceride, cholesterol and free fatty acids) and hyperglycaemia (plasma glucose levels), we have performed genome-wide quantitative traits loci (QTL) analyses of 115 male OLETF x (OLETF x Fischer 344) backcross animals at 16 weeks of age. 3. The Diabetes Mellitus OLETF type I (Dmo1) locus on rat chromosome 1 showed statistically significant involvement in elevations of plasma levels of triglycerides (P = 4.87 x 10(-6) at D1Rat90) and total cholesterol (P = 1.16 x 10(-5) at D1Rat306). 4. No other loci produced significant linkage to these observed phenotypes. 5. These analyses have confirmed the importance of Dmo1 in lipid homeostasis at younger ages as well as during overt diabetes, which appears later. Thus, alterations at the Dmo1 locus are a major risk factor for pathogenesis in the strain, a finding that agrees with physiological studies that indicate a role for dyslipidaemia in the type II diabetic syndrome of OLETF rats.

Animals↗

PubMed2000

Reappraisal of orthodox histochemistry for the diagnosis of minimal deviation adenocarcinoma of the cervix.

Minimal deviation adenocarcinoma (MDA), or adenoma malignum, of the uterine cervix is a diagnostically problematic disease because of the difficulty in differentiating it histologically from normal cervical glands. To evaluate the use of mucin phenotyping for differentiating MDA from other conditions, we performed alcian blue pH 2.5/periodic acid-Schiff (AB-PAS) staining and high iron diamine (HID)-AB staining on routinely processed sections of 11 MDAs, 20 unremarkable cervical glands, 9 cervical glandular hyperplasias occurring in association with mucinous ovarian tumors, and 41 conventional cervical adenocarcinomas. In all 11 MDAs and 11 conventional cervical adenocarcinomas, the tumor cell cytoplasm was stained diffusely red by PAS, indicating that MDA cells produce neutral mucin almost exclusively. The amount of acid mucins, both sulfomucin and sialomucin, was decreased markedly by HID-AB. For four MDAs, preoperative biopsy specimens also showed diffuse cytoplasmic neutral mucin. In contrast, the cytoplasm of constituent cells was stained purple to violet by AB-PAS in all unremarkable cervical glands and glandular hyperplasias, indicating that both acid and neutral mucins were produced in equal amounts, sulfomucin being stained predominantly by HID-AB. Of the 30 conventional cervical adenocarcinomas, 28 showed both acid and neutral mucins and two showed acid mucin only in goblet cells, or in part of the cytoplasm or cell surface of constituent cells, where acid mucin consisted predominantly of sulfomucin in 14 and sialomucin in 16. AB-PAS and HID-AB are simple and orthodox histochemical methods which are effective for differential diagnosis of MDA and can contribute to its early detection and treatment.

Adenocarcinoma↗

PubMed2000

Primary meningeal sarcomas with leiomyoblastic differentiation: a proposal for a new subtype of primary meningeal sarcomas.

Two cases of primary meningeal sarcoma with leiomyoblastic differentiation are presented. In case no. 1, the tumor showed anaplastic spindle cell tumor components intermingled with anaplastic meningothelial components. Meningothelial tumor cells gradually became transformed into spindle tumor cells. Spindle tumor cells reacted with antisera to muscle actin (HHF-35) and alpha-smooth muscle actin. However, unchanged meningothelial tumor cells did not react with the antisera to HHF-35 and alpha-smooth muscle actin. Electron microscopy showed condensations of cytoplasmic fibers and pinocytotic vesicles in spindle tumor cells similar to those seen in smooth muscle cells. In case no. 2, the tumor cells consisted predominantly of sheets of round or polygonal cells as seen in an epithelioid leiomyosarcoma. The neoplastic cells had frequent nuclear inclusions, such as those seen in meningiomas. Immunohistochemically, the tumor cells reacted with antisera to desmin and to HHF-35. Electron microscopy showed a basal lamina around the cytoplasm of tumor cells. Intranuclear inclusions with various cytoplasmic organelles were frequently observed in the tumor cells, as in meningiomas. Interdigitating cytoplasmic processes and intercellular junctional complexes, however, were not found in the tumor cells. Two possible hypotheses explain the occurrence of leiomyoblastic characteristics of these cases. In case no. 1, leiomyoblastic cells originated from meningothelial cells with the advancement of meningothelial anaplasia. In case no. 2, pluripotential mesenchymal cells in the meninges differentiated into meningothelial and smooth-muscle cell lines at the time of tumor growth. With consideration of previous publications on primary meningeal sarcoma, these cases are the first reported primary meningeal sarcoma with leiomyoblastic and meningothelial differentiation.

Aged↗

PubMed2000

A nonpeptide mimic of bradykinin blunts the development of hypertension in young spontaneously hypertensive rats.

We tested whether FR190997, a nonpeptide B(2) agonist, prevented the development of hypertension in young spontaneously hypertensive rats (SHR), which secrete less kallikrein into the urine than do Wistar-Kyoto rats. An intra-arterial (IA) injection of FR190997 (0.3 to 30 nmol/kg) caused dose-dependent hypotension in conscious Sprague-Dawley rats. Although the maximum hypotensive potency of FR190997 equaled that of bradykinin, its action lasted approximately 10 times as long. Hoe140 (100 nmol/kg IA) significantly blocked the hypotensive response induced by FR190997 (10 nmol/kg). Atropine (100 nmol/kg IA) did not affect this response. A selective infusion of FR190997 into the renal artery induced natriuresis and diuresis in anesthetized rabbits. A continuous infusion (2 nmol. 10 mL(-1). h(-1) per rat) of FR190997 into the abdominal aorta of young SHR (6 weeks old, n=6) for 6 days significantly (P<0.05) reduced mean blood pressure to 114+/-6 (day 2) and 110+/-6 (day 5) mm Hg, from 149+/-7 and 162+/-6 mm Hg, respectively, in vehicle-infused rats (n=6). At 8 days after continuous infusion (day 14), mean blood pressure (148+/-5 mm Hg) in FR190997-infused rats remained significantly (P<0. 05) lower than that in vehicle-infused rats (190+/-6 mm Hg), almost the peak value. The mesenteric artery isolated from FR190997-treated rats (day 14) had lower contractile sensitivity to norepinephrine than that from vehicle-treated rats. These results suggested that the continuous infusion of a nonpeptide B(2) agonist may prevent hypertension if performed in the critical phase.

Age Factors↗

PubMed2000

[Two cases of epidural neulolysis using ethyl alcohol and histopathologic changes in the spinal cord].

We report two cases of cancer pain treated with transcatheter thoracic epidural neurolysis using ethyl alcohol, and epidural histopathologic changes in the spinal cord observed in one of the patients. Case 1: A 59-year-old woman complained of intractable right thoracic back pain due to mediastinal osteo-sarcoma. After obtaining pain relief by epidural block using local anesthetics, we did transcatheter thoracic epidural alcohol block using 2-4 ml of 75-100% ethyl alcohol for three times. Her VAS score decreased from 8/10 to 2/10 and the good pain control was obtained until her death 24 days after the third block. After obtaining permission from her family, necropsy was performed. Spinal nerve roots and the spinal cord showed no abnormality. But the laminar structure of the dura had been destroyed at the outer one third of the dura. Case 2: A 49-year old woman suffered from right upper abdominal pain due to giant metastatic liver tumor. We performed twice transcatheter thoracic epidural neurolysis using 2-3 ml of 75% ethyl alcohol. Her VAS score decreased from 7/10 to 3/10 and the pain relief was maintained until her death 2.5 months after the neurolysis. Motor palalysis was not observed in both cases.

Analgesia, Epidural↗

PubMed1999

Specific interaction between DNA polymerase II (PolD) and RadB, a Rad51/Dmc1 homolog, in Pyrococcus furiosus.

Pyrococcus furiosus has an operon containing the DNA polymerase II (PolD) gene and three other genes. Using a two-hybrid screening to examine the interactions of the proteins encoded by the operon, we identified a specific interaction between the second subunit of PolD (DP1) and a Rad51/Dmc1 homologous protein (RadB). To ensure the specific interaction between these two proteins, each gene in the operon was expressed in Escherichia coli or insect cells separately and the products were purified. The in vitro analyses using the purified proteins also showed the interaction between DP1 and RadB. The deletion mutant analysis of DP1 revealed that a region important for binding with RadB is located in the central part of the sequence (amino acid residues 206-498). This region has an overlap to the C-terminal half (amino acids 334-613), which is highly conserved among euryarchaeal DP1s and is essential for the activity of PolD. Our results suggest that, although RadB does not noticeably affect the primer extension ability of PolD in vitro, PolD may utilize the RadB protein in DNA synthesis under certain conditions.

Animals↗

PubMed1999

Carcinogenic effects of N-ethyl-N-hydroxyethylnitrosamine and its metabolites in rats and mice.

N-ethyl-N-hydroxyethylnitrosamine (EHEN), a member of the nitrosamine class of carcinogens induces renal cancer. However, since very little is known about the metabolic products of EHEN and their effects, these were investigated in rats and mice. EHEN, N-ethyl-N-formylmethylnitrosamine (EFMN) and N-ethyl-N-carboxymethyl-nitrosamine (ECMN) were administered in the drinking water for 2 weeks and the animals were then maintained until sacrifice at week 32. The urine of the rats was collected over the 2-week exposure period and analyzed by HPLC. The results showed that EHEN but not EFMN or ECMN induces tumors in the kidneys of rats. In mice the lungs were targeted not only by the parent compound but also by both metabolites. The findings suggest that the kidney is the most susceptible organ to EHEN effects in the rat while the lung is the most susceptible organ in mice. These results are consistent with inter-species variation in the metabolism of xenobiotics.

Animals↗

PubMed1999

Facilitation of renal kallikrein-kinin system prevents the development of hypertension by inhibition of sodium retention.

We have previously reported that the renal kallikrein-kinin system suppressed the development of hypertension, using kininogen deficient Brown Norway Katholiek rats. Kinins were degraded in urine mainly by carboxypeptidase Y-like kininase (CPY). Blockade of renal kinin degradation may prevent the experimental hypertension through the facilitation of the renal kallikrein-kinin system. Daily administration of ebelactone B (EB), which is isolated from Actinomycetes and strongly inhibits CPY, from the first day of deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks completely blocked hypertension in Sprague-Dawley rats. This treatment reduced sodium levels in erythrocytes and cerebrospinal fluids (CSF) significantly. By contrast, an ACE inhibitor, lisinopril did not prevent hypertension. The development of hypertension in young spontaneously hypertensive rats was also blunted by EB with reductions in sodium levels in erythrocytes and in CSF. The arterial kinin levels in rats undergoing DOCA-salt treatment were 2.2 +/- 0.2 pg/ml, which were increased significantly to 4.6 +/- 0.4 pg/ml with captopril (10 mg/kg, s.c.). The increased kinin levels were less than those to show hypotension. EB did not increase the arterial kinin levels, with significant increase in urinary kinin secretion. These results suggested that facilitation of the renal kallikrein-kinin system by inhibition of kinin degradation on the luminal side of the renal tubules may effectively prevent hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

K+ loading, but not Na+ loading, and blockade of ATP-sensitive K+ channels augment renal kallikrein secretion.

This study aimed to examine whether K+ loading or Na+ loading augments renal kallikrein (KK) secretion. It also investigated the effect of blockade of renal ATP-sensitive K+ channels on renal KK secretion. Rats were administered 50 mmol/kg body weight of KCl. Twelve-hour collected urine was measured for urinary excretion of K+ and Na+ and urinary activity of renal KK. Increases in urinary excretion of K+ and Na+ by K+ loading accompanied an increase in renal KK secretion. In another experiment, rats were infused intravenously with a solution of 75 mM K+ and 75 mM Na+, 150 mM Na+ or 300 mM Na+ for 150 min under anesthesia. Urinary KK activity was measured in urine collected every 30 min. Renal KK secretion began to increase within the 30 min infusion of K+ solution and persisted at more elevated levels during the infusion with K+ solution than with Na+ solutions. Furthermore, rats were given intravenous injection of ATP-sensitive K+ channel blocker, either PNU-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl) at a concentration of 10 mg/kg or glibenclamide at 30 mg/kg. Renal KK secretion increased 30 min after administration of both PNU-37883A and glibenclamide. In conclusion, it may be that augmentation of renal KK secretion by K+ loading occurred through an increase in urinary K+ excretion followed by the inhibition of K+ transport from ATP-sensitive K+ channels.

ATP-Binding Cassette Transporters↗

PubMed1999

A secretory mechanism of renal kallikrein by a high potassium ion; a possible involvement of ATP-sensitive potassium channel.

A relatively rapid excretion of urinary kallikrein into urine was observed by an intravenous infusion of high potassium in anesthetized rats. Superfusion of sliced cortex isolated from rat kidney with an isotonic solution containing more than 20 mM of KCl significantly stimulated the release of kallikrein. The latter in vitro result supported another mechanism for the release of renal kallikrein from kidney other than biosynthesis of kallikrein by aldosterone released from adrenal cortex after loading of high potassium and the mechanism was elucidated. ATP-sensitive potassium channel blockers, glibenclamide, 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U37883A), and barium chloride, which inhibit an efflux of intracellular potassium to block the channel, showed a significant increase of the kallikrein release from the slice of kidney cortex. Cytochalasin B, which inhibits a polymerization of actin, also showed a stimulation of the release. Enhanced release of kallikrein by a high potassium or ATP-sensitive potassium channel blocker was reduced by the absence of calcium ion and the presence of voltage-dependent calcium channel blocker in the superfused solution. These results indicate the ATP-sensitive potassium channel which couples to voltage-dependent calcium channel and cytoskeletal protein could be involved in a rapid secretory mechanism of renal kallikrein by high potassium.

ATP-Binding Cassette Transporters↗

PubMed1999

Functional beta1-integrins release the suppression of fibronectin matrix assembly by vitronectin.

beta1-null GD25 fibroblasts adherent to vitronectin fail to bind the N-terminal 70-kDa matrix assembly domain of fibronectin or to assemble fibronectin (Sakai, T., Zhang, Q., Fässler, R., and Mosher, D. F. (1998) J. Cell Biol. 141, 527-538). We have made four observations that extend this finding. First, the presence of vitronectin on a substrate that otherwise can support fibronectin assembly has a dominant-negative effect on assembly. Second, the dominant-negative effect is lost when active beta1A is expressed. Third, beta1A containing the extracellular D130A inactivating mutation has a dominant-negative effect on fibronectin assembly. Fourth, beta1-null cells adherent to vitronectin are flat and lack filopodia, whereas beta1-null cells adherent to fibronectin or beta1A-expressing cells adherent to either vitronectin or fibronectin are contracted and exhibit numerous filopodia. These results reveal, therefore, that GD25 cells adherent to vitronectin can only assume a shape suitable for assembly of fibronectin when there is a countervailing signal from functional beta1-integrins.

Amino Acid Sequence↗

PubMed1999

Left antero-axillary thoracotomy as an alternative approach for aortic arch reconstruction.

Antero-axillary thoracotomy--a new approach for the reconstruction of the aortic arch--provides a wide view of the arch and makes accessible the superior vena cava for retrograde cerebral perfusion as well as the coronary sinus for retrograde infusion of cardioplegia. This procedure has been used over 22 months for 26 patients with aortic arch aneurysm or aortic dissection, and the surgical results were evaluated. The distal arch was replaced in 16 patients, the total arch in 9 patients, and the proximal arch in 1 patient, using this technique. The mean duration of deep hypothermic circulatory arrest was 38 min, and the hospital mortality was 15.4%. Antero-axillary thoracotomy may be an excellent approach for the reconstruction of the aortic arch, minimizing the duration of hypothermic circulatory arrest.

Aortic Dissection↗

PubMed1999

Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists.

1. Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws. 2. Up to 100 microg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method. 3. Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid. 4. Treatment with aprotinin to inhibit tissue kallikrein reduced the scratching behaviour induced by sodium deoxycholic acid, whereas treatment with soybean trypsin inhibitor to inhibit plasma kallikrein did not. 5. Although injection of kininase II inhibitor, lisinopril together with sodium deoxycholic acid did not alter the scratching behaviour, phosphoramidon, a neutral endopeptidase inhibitor, significantly increased the frequency of scratching. 6. Homogenates of the skin excised from the backs of mice were subjected to gel-filtration column chromatography followed by an assay of kinin release by trypsin from each fraction separated. Less kinin release from the fractions containing kininogen of low molecular weight was observed in the skin injected with sodium deoxycholic acid than in normal skin. 7. The frequency of scratching after the injection of sodium deoxycholic acid in plasma kininogen-deficient Brown Norway Katholiek rats was significantly lower than that in normal rats of the same strain, Brown Norway Kitasato rats. 8. These results indicate that BK released from low-molecular-weight kininogen by tissue kallikrein, but not from high-molecular-weight kininogen by plasma kallikrein, may be involved in the scratching behaviour induced by the injection of sodium deoxycholic acid in the rodent.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Effect of prolonged administration of a urinary kinase inhibitor, ebelactone B on the development of deoxycorticosterone acetate-salt hypertension in rats.

The effect of prolonged administration of a carboxypeptidase Y-like kininase inhibitor, ebelactone B (EB) (2-ethyl-3, 11-dihydroxy-4, 6, 8, 10, 12-pentamethyl-9-oxo-6-tetradecenoic 1, 3-lactone), on the development of deoxycorticosterone acetate (DOCA)-salt hypertension was tested. The systolic blood pressure (SBP) of non-treated 6-week-old Sprague-Dawley strain rats was gradually increased by DOCA-salt treatment from 137+/-2 mmHg (n=11) to 195+/-7 mmHg at 10 weeks of age. With daily oral administration of lisinopril (5 mg kg(-1), twice a day), which is an inhibitor of angiotensin converting enzyme, a major kininase in plasma, the development of hypertension was not suppressed. By contrast, administration of EB (5 mg kg(-1), twice a day), completely inhibited the development of hypertension (SBP: 146+/-1 mmHg, n=5, 10 weeks old). The reduced SBP at 10 weeks of age was equal to the SBP before any treatment (142+/-1 mmHg, n=5). Direct determination of mean blood pressure (MBP) in conscious, unrestrained rats confirmed that MBP elevation was completely inhibited by EB. Continuous subcutaneous infusion (5 mg kg(-1) day(-1)) of HOE140, a bradykinin B2 receptor antagonist, restored the elevation of SBP, which was suppressed by EB. The weights of left ventricle of DOCA-salt treated rats 10-weeks-old (0.36+/-0.02 g 100 g body weight(-1), n=11) was significantly reduced by EB (0.27+/-0.01, n=5), as were the sodium levels in serum, cerebrospinal fluid and erythrocyte. These findings suggested that EB is effective in preventing salt-related hypertension presumably by eliminating sodium retention.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Early increases in renal kallikrein secretion on administration of potassium or ATP-sensitive potassium channel blockers in rats.

1 This study aimed to examine whether administration of potassium or ATP-sensitive potassium channel (KATP channel) blockers caused early increases in renal kallikrein (KK) secretion. To clarify this mechanism, the effect on renal KK secretion of a KATP channel blocker was compared with the effect resulting from use of an osmotic diuretic or volume load. Furthermore, the effect on potassium-induced increases in renal KK secretion by an additional treatment using a KATP channel blocker was examined. Lastly, the effect of a KATP channel blocker on renal KK secretion was also examined in superfused slices of kidney cortex. 2 Intravenous infusion of potassium augmented renal KK secretion within 30 min while urine volume increased gradually in both the potassium loading and control groups. 3 Administration of the KATP channel blocker, 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (PNU-37883A) or glibenclamide, caused a dose-dependent increase in renal KK secretion. 4 The concentration of KK in urine was higher in the PNU-37883A group as compared to the osmotic-diuretic or volume-load group. 5 PNU-37883A had no additive effect on the potassium-induced increase in renal KK secretion. 6 Renal KK secretion increased in slices of kidney cortex incubated with PNU-37883A within 10 min of superfusion. 7 In conclusion, administration of both potassium and KATP channel blockers induced early increases in renal KK secretion in the absence of the washout phenomenon. Potassium loading may have increased renal KK secretion through the same mechanism as the KATP channel blocker.

Adamantane↗