bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROLE OF INTRACELLULAR SIGNALLING PATHWAYS IN HYDROGEN PEROXIDE‐INDUCED INJURY TO RAT GLOMERULAR MESANGIAL CELLS
Authors: Shaw Sidney , Naegeli Patricia , Etter Jean‐Daniel , Weidmann Peter 
Published: June 2007

SUMMARY1. Brief exposure of cultured rat glomerular mesangial cells (GMC) to H202 in nominally bicarbonate‐free solution induced a rapid dose dependent, dantrolene‐inhibitable increase in intracellular free Ca2+ from 65 ± 6 to 203 ± 14 nmol/L and a prolonged release of [14C]‐arachidonic acid [14C]‐AA which preceded the onset of cell membrane damage assessed by trypan‐blue uptake.2. Ca2+ responses were potentiated in HCO3−/CO2 containing buffers and reached values of 1145 ± 100 nmol/L at 1 mmol/L H2O2. In HCO3−/CO2 solutions, but not HEPES buffer, HzOz‐induced Ca2+ increases were markedly attenuated by verapamil (100 μmol/L) or removal of extracellular calcium.3. Enhanced release of [14C]‐AA was partially attenuated by inhibitors of key intracellular signalling mechanisms including the phospholipase‐A2 (PLA2) inhibitor mepacrine (100 μmol/L), the NADPH oxidase inhibitor diphenyliodonium (10 μmol/L), the mitochondrial calcium‐cycling inhibitor ruthenium red (100 μmol/L) and the iron chelator dipyridyl (100 μmol/L). Release was unaffected by protein kinase C inhibition with H7 (100 μmol/L), inositol triphosphate antagonism with neomycin (1 mmol/L) or overnight treatment with the G‐protein antagonist pertussis toxin (5 μg/mL).4. Several structurally diverse lipoxygenase inhibitors, including esculetin, baicalein and phenidone, over the dose range 1–100 μmol/L, also prevented [14C]‐AA release and markedly protected against cell membrane damage. No drug directly scavenged H202 assessed by UV absorption.5. These results indicate that H2O2 activates in GMC a complex series of interrelated pathological mechanisms which in turn contribute to a prolongation of oxidative damage beyond the time of the initial exposure. These include an increase in intracellular calcium which, depending upon conditions, appears to be mediated by release from intracellular stores as well as Ca2+ entry from the extracellular space. In turn there is a sustained release of arachidonic acid, which may partly depend on prolonged activation of PLA2 but not phospholipase C.6. Release of [14C]‐AA could be attenuated by inhibitors of NADPH oxidase, mitochondrial calcium‐cycling, iron chelators and a structurally diverse range of lipoxygenase inhibitors in association with protection from H2Otrnediated cell membrane damage.
PROTON AND POTASSIUM TRANSPORT BY H+/K+‐ATPases
Authors: van Driel Ian R. , Callaghan Judy M. 
Published: June 2007

SUMMARY1. H+/K+‐ATPases are members of the P‐type ATPase multigene family. The prototypical H+/K+‐ATPase is the protein that acidifies gastric luminal contents. The physiological and pharmacological significance of this pump has led to a detailed investigation of its biochemistry and molecular and cell biology.2. Recently, a number of closely related H+/K+‐ATPase isoforms have been discovered. These isoforms are present in organs other than the stomach, including the colon and kidney, where they contribute to acid—base and potassium homeostasis. The structure, expression and physiological roles of the gastric H+/K+‐ATPase and other isoforms are reviewed.
NOVEL MUTATION IN THE FIRST INTRON OF THE SPONTANEOUSLY HYPERTENSIVE RAT RENIN GENE UPSTREAM OF THE TANDEM REPEAT ELEMENT
Authors: Di Nicolantonio R. , Yu H. , Wilks A. , Lan L. 
Published: June 2007

Summary1. The first 1100 base pairs of the first intron of the renin gene was amplified from the spontaneously hypertensive rat (SHR), Wistar‐Kyoto (WKY) and Sprague‐Dawley (SD) rats. A Bgl II restriction fragment length polymorphism (RFLP) was identified in this region of the SHR renin gene.2. Sequence analysis located the Bgl II RFLP between positions 500 and 505 of the reported rat renin gene. The new Bgl II cut site was produced by a single base mutation from G to A.3. Whether this mutation in the first intron of the SHR renin gene plays a role in the reported overexpression of the renin gene in this strain remains to be elucidated.
PLATELET‐DERIVED GROWTH FACTOR B‐CHAIN COMPRISES THE MAJOR PART OF ENHANCED RELEASED MITOGEN FROM AORTIC ENDOTHELIAL CELLS OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Sasahara M. , Hayase Y. , Yang X. H. , Iihara K. , Amano S. , Hazama F. 
Published: June 2007

Summary1. The present study was conducted to analyse the release and production of mitogen in cultured aortic endothelial cells of stroke‐prone spontaneously hypertensive rats (SHRSP), for the further understanding of the role of arterial endothelial cells in the genesis of vascular lesions in hypertension.2. The cultured aortic endothelial cells derived from SHRSP increased released mitogens were compared with those from control Wistar‐Kyoto rats (WKY) with respect to cultured vascular medial smooth muscle cells and fibroblasts.3. Biochemical analyses determined that the major part of mitogen released from aortic endothelial cells of both SHRSP and controls was the platelet‐derived growth factor B‐chain.4. Further northern analyses revealed that the transcripts of PDGF B‐chain were constitutively accumulated three‐ to fourfold in quiescent aortic endothelial cells from SHRSP, compared with those from WKY through passages 2 to 5.5. However, the half‐lives of the transcripts after actinomy cin D treatment were 1.12 h (s.d. = 0.14,n= 4) and 1.28 h (s.d. = 0.08,n= 3), in SHRSP and in WKY, respectively, showing no significant difference.6. These suggest that the increased accumulated transcripts of PDGF B‐chain in SHRSP are due to an enhanced trans‐criptional rate. These enhanced release and production of PDGF‐B chain in arterial endothelial cells, which may be induced under chronic hypertensive conditions, is suggested to contribute to the genesis of vascular lesion in hypertension, through the stimulation of vascular smooth muscle cell proliferation and hypertrophy.
OCULAR FUNDUS CHANGES IN MALIGNANT OR PRECOCIOUS STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS AFTER ADMINISTRATION OF ANTIHYPERTENSIVE DRUGS
Authors: Hamada Yoh , Niisato Etsurou , Otor Toshifumi , Chikugo Taka‐aki , Ohta Yoshio , Suzuki Tsuneyuki , Okamoto Kozo 
Published: June 2007

Summary1. Malignant or precocious stroke‐prone spontaneously hypertensive rats (M‐SHRSP) showed hypertensive ocular fundus changes with severe hypertension, but various anti‐hypertensive drugs given over a proper period improved funduscopic findings.2. We treated a M‐SHRSP with SQ29, 852 (an angiotensin converting enzyme inhibitor, ACEI) or manidipine (a calcium antagonist) and observed hypertensive vascular changes in the fundus.3. The M‐SHRSP treated with anti‐hypertensive drugs lived longer and the hypertensive fundic changes improved in both groups. But there were some differences of histochemical staining reaction on the endothelial cell‐surface and mucopoly‐saccharides accumulations between the treated group of ACEI and the group treated with the calcium antagonist.4. In the treated group with calcium antagonist, the anionic ion functions of the endothelial cell‐surface were impaired and organic retinal or choroidal damages appeared to have deteriorated.
ROLE OF NITRIC OXIDE IN THE CONTROL OF BLOOD PRESSURE IN YOUNG AND ADULT SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Akiba Y. , Yamaguchi N. , Amano H. , Fujii T. , Fujimoto K. , Suzuki T. , Kawashima K. 
Published: June 2007

Summary1. The depressor response to sodium nitroprusside (SNP) and the pressor response to Nω‐nitro‐L‐arginine methyl ester (L‐NAME) were investigated in anaesthetized and ganglion‐blocked 6 week old (young) and 20 week old (adult) spontaneously hypertensive rats (SHR), and the results were compared with those in age‐matched normotensive Wistar‐Kyoto (WKY) rats.2. SNP produced a dose‐dependent decrease of the mean blood pressure (BP) in both strains, and no differences in vascular sensitivity to SNP were observed between the strains.3. L‐NAME caused dose‐dependent pressor responses in both strains. The sensitivity and the maximal response to L‐NAME in SHR were significantly greater than those in age‐matched WKY (P < 0.05 or 0.01; t‐test, 13d.f. in both ages). However, there were no significant differences in the responses between ages in each strain.4. Acute reduction of BP induced by 7‐O‐ethylfangchinoline did not affect the responses to SNP and L‐NAME in the adult SHR.5. These results indicate that a greater amount of NO is tonically released in SHR and that its contribution to BP control is greater in SHR than in WKY, whereas vascular sensitivity to NO does not differ between the strains. In addition, acute changes in BP do not affect the degree of dependency on NO for BP control.
PROMOTION OF NITRIC OXIDE FORMATION BY HEPARIN IN CULTURED AORTIC ENDOTHELIAL CELLS FROM SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Minami M. , Yokokawa K. , Kohno M. , Ikeda M. , Horio T. , Kano H. , Hanehira T. , Yasunari K. , Takeda T. 
Published: June 2007

Summary1. The present study examined the effect of heparin on nitric oxide (NO) formation and cyclic guanosine 3′, 5′‐monophos‐phate (cGMP) levels in cultured aortic endothelial cells (EC) from spontaneously hypertensive rats (SHR) and normoten‐sive Wistar‐Kyoto (WKY) rats.2. Bradykinin (BK), adenosine diphosphate (ADP), Ca2+ ionophore A23187 (Io) and endothelin‐3 (ET‐3) stimulated the production of NO and cGMP. No significant difference was observed in both NO and cGMP production in EC between WKY and SHR.3. Heparin enhanced BK‐, ADP‐, Io‐ and ET‐3–stimulated NO and cGMP production. These enhancements by heparin in EC were significantly greater in SHR than in WKY.4. Both NO formation and cGMP production stimulated by the agonists and/or heparin were blocked in the presence of NG‐monomethyl‐L‐arginine (LNMMA, 10‐5mol/L).5. Increased sulphur level was observed on heparin‐treated SHR EC surface compared with that on control SHR EC or on heparin‐treated WKY EC surface.6. These results suggest that heparin promotes agonist‐induced NO‐cGMP response in cultured EC from SHR.
CHANGES OF ENDOTHELIAL FUNCTIONS IN THE CORONARY ARTERY AFTER CHRONIC NITROARGININE FEEDING
Authors: Kajimoto Noriyoshi , Ogawa Hiroshi , Suzuki Aritomo 
Published: June 2007

Summary1. The effects of chronic NG‐nitro‐L‐arginine (LNA) feeding on the endothelial function in isolated coronary arteries from stroke‐prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar‐Kyoto (WKY) rats were studied.2. A diet containing LNA (0.02%) was given to male SHRSP and WKY at 6 weeks of age and the coronary arteries were dissected on the 10th day of feeding.3. In the SHRSP and WKY fed the LNA‐free diet, acetyl‐choline (ACh) relaxed the precontracted ring segments of the coronary artery with intact endothelium in a dose‐dependent manner. The reactivity was stronger in the WKY than in the SHRSP. However, the ACh‐induced relaxation after the LNA‐feeding was significantly stronger in the coronary arteries from the WKY than in those from the SHRSP.4. The relaxation induced by the calcitonin gene‐related peptide (CGRP) was endothelium‐dependent and endothelium‐independent. The degree of the response in the rats fed the LNA‐containing diet was not significantly different from that in the rats fed the LNA‐free diet.5. The vasodilator response induced by sodium nitroprusside (SNP) was dose‐dependent and similar in the rats fed the LNA containing diet and the LNA‐free diet.6. These findings indicate that chronic LNA feeding markedly impaired the endothelial nitric oxide formation in the coronary artery from young SHRSP.
REGIONAL DISTRIBUTION OF SUPEROXIDE DISMUTASE IN THE BRAIN AND MYOCARDIUM OF THE STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Kimoto S. , Nishida S. , Funasaka K. , Nakano T. , Teramoto K. , Tomura T. T. 
Published: June 2007

Summary1. Enzyme activities and contents of manganese and copperzinc superoxide dismutase (Mn‐, Cu/Zn‐SOD) and oxygen free‐radical scavengers were determined in the myocardium (right, left ventricle) and brain (cerebral cortex, hippocampus) of 15 and 31 week old stroke‐prone spontaneously hypertensive rats (SHRSP).2. In 15 week old SHRSP myocardium, both Mn‐ and Cu/Zn‐SOD activities were higher but in 31 week old SHRSP, these were lower than that in Wistar‐Kyoto (WKY) rats. Further, correlation between Mn‐SOD content and activity in 31 week old SHRSP myocardium showed that specific activity was lower than that in WKY.3. In 15 and 31 week old SHRSP cerebral cortex and hippocampus, SOD content and activity showed a tendency to be lower than that in WKY.4. These results indicate that enzymatically inactive or low‐active Mn‐SOD protein exists in SHRSP myocardium, and that the alteration of SOD may be one of the causative factors for the vulnerability of the myocardium and brain against O2‐radicals.
RELATIONSHIP BETWEEN ERYTHROCYTES GLUTATHIONE PEROXIDASE AND INCIDENCE OF STROKE LESION IN THE STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Murakami Tetsuo , Takemori Kumiko , Takeda Tohru , Yoshizumi Hajime 
Published: June 2007

Summary1. To determine biochemically the incipient timing of cerebral stroke in stroke‐prone spontaneously hypertensive rats (SHRSP) the relation between the glutathione peroxidase (GSH‐Px) activity in erythrocytes and the extent of stroke lesion was investigated.2. When the blood pressure of SHRSP was maintained over 250 mmHg, the GSH‐Px activity was lowered and the body‐weight also decreased. In the SHRSP where the GSH‐Px activity in erythrocytes dropped below 23 units/mL blood, the incidence of cerebral stroke was 98% (n= 88/90).3. The haemoglobin and haematocrit level were unchanged even after the GSH‐Px activity dropped to 23 units/mL blood.4. Lowering of GSH‐Px activity in erythrocytes observed during continued hypertension was found to be due to decreased GSH‐Px protein, but not to an inactivation of enzymes, as evidenced from immunochemical titration.5. Lowering of GSH‐Px activity in erythrocytes was found to be closely related with the incidence of cerebral stroke in SHRSP. These findings suggest that tracing of the GSH‐Px activity in erythrocytes in SHRSP may serve as an indicator for prediction and prognosis of stroke lesion.
ALTERNATIVE SPLICING OF NATRIURETIC PEPTIDE A AND B RECEPTOR TRANSCRIPTS IN THE RAT BRAIN
Authors: Francoeur F. , Gossard F. , Hamet P. , Tremblay J. 
Published: June 2007

Summary1. In the present study we searched for variants of alternative splicing of guanylyl cyclase A and B mRNA in rats in vivo.2. Guanylyl cyclase A2 and guanylyl cyclase B2 isoforms of guanylyl cyclase produced by alternative splicing leading to the deletion of exon 9 of both transcripts were quantified in several rat organs.3. Only one alternative splicing was found in the regulatory domain, encoded by exons 8–15.4. Quantification of the guanylyl cyclase B2 isoform in different rat organs and in cultured aortic smooth muscle cells showed that this alternative splicing was tissue‐specific and occurred predominantly in the central nervous system where the alternatively spliced variant represented more than 50% of the guanylyl cyclase B mRNA.5. The same alternative splicing existed for guanylyl cyclase A mRNA but at very low levels in the organs studied.6. Alternative splicing of guanylyl cyclase B exon 9 in the brain may play an important role in signal transduction, since the expressed protein possesses a constitutionally active guanylyl cyclase acting independently of C‐type natriuretic peptide regulation.
ALTERED GENE EXPRESSION OF NATRIURETIC PEPTIDE RECEPTOR SUBTYPES IN THE KIDNEY OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Goto Masahisa , Itoh Hiroshi , Tanaka Issei , Suga Shin‐ichi , Ogawa Yoshihiro , Kishimoto Ichiro , Nakagawa Masayo , Sugawara Akira , Yoshimasa Takaaki , Mukoyama Masashi , Nakao Kazuwa 
Published: June 2007

Summary1. To elucidate the physiological and pathophysiological role of the natriuretic peptide system in the progression of hypertensive renal disease, we examined the gene expression of natriuretic peptide receptor subtypes, guanylate cyclase‐A (GC‐A), guanylate cyclase‐B (GC‐B) and clearance receptor (C receptor), in the kidney of stroke‐prone spontaneously hypertensive rats (SHRSP) at 8 and 20 weeks of age, and compared them with their gene expression in age‐matched Wistar‐Kyoto (WKY) rats.2. Northern blot analyses revealed that messages for three natriuretic peptide receptor subtypes were expressed in the kidney, and their expressions were higher in the glomeruli than in the whole kidney in each strain.3. In 20 week old rats with established hypertension, the glomerular concentration of GC‐A mRNA was significantly higher in SHRSP than in WKY. The concentrations of GC‐B and C receptor mRNA in the glomeruli tended to increase and decrease, respectively, but they were not statistically significant in SHRSP.4. In 8 week old rats, the glomerular concentrations of GC‐A, GC‐B and C receptor mRNA were not significantly different between SHRSP and WKY.5. This study demonstrates that in the progression of hypertension, the expression of GC‐A, which mediates biological actions of natriuretic peptides, is enhanced in the kidney of SHRSP compared to that of WKY. Together with the augmented secretion of the ligands previously revealed, altered expression of natriuretic peptide receptor subtypes in SHRSP may have a deterrent role in the development of hypertension and its renal complications.
PREPARATION OF A MONOCLONAL ANTIBODY AGAINST MOUSE BRAIN NATRIURETIC PEPTIDE (BNP) AND TISSUE DISTRIBUTION OF BNP IN MICE
Authors: Nakagawa Masayo , Tanaka Issei , Suga Shin‐ichi , Ogawa Yoshihiro , Tamura Naohisa , Goto Masahisa , Sugawara Akira , Yoshimasa Takaaki , Itoh Hiroshi , Mukoyama Masashi , Nakao Kazuwa 
Published: June 2007

Summary1. In order to explore the significance of brain natriuretic peptide (BNP), a cardiac hormone secreted from the ventricle, in mice, we prepared a monoclonal antibody against mouse BNP (mBNP) and established a specific radioimmunoassay (RIA) for mBNP.2. A monoclonal antibody, KY‐mBNP‐I, was prepared by the fusion of mouse myeloma cells X63‐Ag8.653 with spleen cells of the BALB/c mouse immunized with synthetic mBNP[108–121] conjugated to bovine thyroglobulin. KY‐mBNP‐I belonged to an IgG2a subclass and showed a high affinity for mBNP(Ka = 1.8 × 1011 mol/L−l).3. The RIA established that using KY‐mBNP‐I was highly sensitive and specific for mBNP, with an IC50 value of 3 fmol/ tube and cross‐reactivities of less than 0.003% with related natriuretic peptides. mBNP‐like immunoreactivity (mBNP‐LI) was detected in the mouse atrium (0.35 ± 0.02 nmol/g), ventricle (20.5 ± 0.5 pmol/g) and kidney (0.50 ± 0.05 pmol/g), but not in other tissues including brain.4. Gel filtration analysis revealed that the major component of tissue mBNP‐LI was co‐eluted with synthetic mBNP[77–1211, a 45‐amino acid mature peptide.5. The monoclonal antibody and RIA for mBNP established here will provide useful tools to investigate the functional significance of BNP in mice, coupled with the genetic engineering approach.
ENDOTHELIN‐1 GENE EXPRESSION AND VASCULAR HYPERTROPHY IN DOCA‐SALT HYPERTENSION COMPARED TO SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Schiffrin Ernesto L. , Larivière Richard , Li Jin‐Sheng , Sventek Pavol , Touyz Rhian M. 
Published: June 2007

Summary1. Enhanced endothelin‐1 gene expression has been found in blood vessels of deoxycorticosterone acetate (DOCA)‐salt hypertensive rats. In this study, the effects of salt, DOCA and the development of hypertension in DOCA‐salt hypertensive rats on the expression of the endothelin‐1 gene in blood vessels and on vascular hypertrophy were compared in Sprague‐Dawley (SD) rats and spontaneously hypertensive rats (SHR).2. Increased endothelin‐1 mRNA was found by northern blot analysis in the mesenteric arterial bed of DOCA‐salt hypertensive rats and DOCA‐salt SHR, but not in DOCA or salt‐treated SD rats or in SHR, even when blood pressure reached a mean of 211 mmHg in DOCA‐treated SHR.3. Vascular structure was studied in small mesenteric arteries mounted on a wire myograph. The media width to lumen diameter ratio showed a close correlation with systolic blood pressure except in DOCA‐salt hypertensive rats and DOCA‐salt SHR, in which it was greater than accounted for by the level of blood pressure. Treatment of DOCA‐salt hypertensive rats with the combined ETA/ETB endothelin antagonist bosentan lowered blood pressure slightly, but vascular hypertrophy regressed almost completely and any hypertrophy remaining could be explained by the residual elevated blood pressure.4. In conclusion, SHR do not exhibit enhanced expression of endothelin‐1 in blood vessels. DOCA, salt and elevated blood pressure interact to induce increased arterial expression of endothelin‐1. Vascular overexpression of the endothelin‐1 gene may produce vascular hypertrophy independently of blood pressure elevation.
URINARY EXCRETION OF 19‐NORALDOSTERONE IN THE SPONTANEOUSLY HYPERTENSIVE RAT AND STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Takeda Yoshiyu , Miyamori Isamu , Yoneda Takashi , Hurukawa Kenji , Inaba Satoru , Ito Yuji , Takeda Ryoyu 
Published: June 2007

Summary1. We measured the urinary excretion of 19‐noraldosterone in the spontaneously hypertensive rat (SHR) and stroke‐prone SHR (SHRSP) during the development of hypertension and compared these measurements with Wistar‐Kyoto (WKY) rats.2. 19‐Noraldosterone in rat urine was confirmed using HPLC‐MS. Urine samples were collected from 4 and 9 week old SHR (n= 12), SHRSP (n= 12) and WKY rats (n= 9). 19‐Noraldosterone was measured by specific radio immunoassay after purification of the urine extracts with HPLC.3. There were no significant differences in plasma corticosterone among SHR, SHRSP and WKY rats at 4 and 9 weeks of age. Aldosterone levels were increased in the prehypertensive SHR and SHRSP. Nine week old SHRSP showed high plasma concentration of aldosterone compared with SHR or WKY rats of the same age.4. Urinary excretion of 19‐noraldosterone was increased in 4 week old SHR (15 ± 4.2 pmol/day) and SHRSP (17 ± 5.0 pmol/day) compared with WKY rats (9 ± 3.9 pmol/day) at the same age. Nine week old SHR showed decreased urinary excretion of 19‐noraldosterone compared with WKY rats at the same age. Urinary levels of 19‐noraldosterone were higher in SHRSP (11 ± 4.9 pmol/day) than in SHR (7 ± 4.0 pmol/day) at 9 weeks of age.5. Adrenal mineralocorticoids are suggested to be responsible for the abnormal vascular reactivity observed in SHRSP. Relatively elevated levels of 19‐noraldosterone in SHRSP may contribute to malignant hypertension in this model.
LIPID MEDIATORS AND PROTEIN KINASE C FOR INTRACELLULAR SIGNALLING
Authors: Nishizuka Yasutomi , Nakamura Shun‐ichi 
Published: June 2007

Summary1. The stimulation of a cell surface receptor initiates a degradation cascade of various membrane lipid constituents.2. Many of their metabolites have potentials to induce, intensify and prolong the activation of protein kinase C that is needed for sustained cellular responses.