bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEMONSTRATION OF HEREDITARILY ACCELERATED PROLIFERATION IN ASTROCYTES DERIVED FROM SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Yamagata Kazuo , Nara Yasuo , Tagamit Motoki , Yamorit Yukio 
Published: June 2007

SUMMARY1. We examined the proliferative rates of cultured astrocytes isolated from stroke‐prone spontaneously hypertensive rats (SHRSP) and stroke‐resistant spontaneously hypertensive rats (SHRSR). Wistar‐Kyoto rats (WKY) were used as a control for SHRSP and SHRSR.2. In the presence of 10% fetal bovine serum (FBS), the doubling time for astrocytes from SHRSP and SHRSR was significantly shorter than WKY.3. When quiescent astrocytes derived from SHRSP or SHRSR were released from serum‐deprivation, the DNA synthesis was stimulated 13.3‐fold and 12.5‐fold, respectively, whereas only a 7.76‐fold increase was observed in WKY astrocytes.4. Further we studied the effects of two growth factors, epidermal growth factor (EGF) and fibroblast growth factor (FGF) on astrocyte proliferation. EGF induced greater DNA synthesis in SHRSP and SHRSR astrocytes compared with WKY astrocytes, although FGF had little or no effect.5. Total cholesterol levels in SHRSP astrocytes and SHRSR astrocytes were significantly lower than that of WKY astrocytes, which was consistent with our previous observations in cultured vascular smooth muscle cells.6. There was no differece in morphology among the cultured astrocytes from the three strains.7. The abnormality of growth rate and cell membranes composition of astrocytes might be closely related to the genetic phenotypes (acute death of neurons and oedema of astrocytes) of SHRSP or SHRSR.
ACUTE EFFECT OF ETHANOL ON RENAL ELECTROLYTE TRANSPORT IN THE RAT
Authors: Carney Shane L. , Gillies Alastair H. B. , Ray Cheryl D. 
Published: June 2007

SUMMARY1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso‐pressin (AVP) release.2. Ethanol at a plasma concentration of 1.69 ±0.28 mmol/L produced an immediate increase in urine flow (174 ± 11 μL/min pre‐ethanol and 189 ± 13 and then 206 ± 12 μL/min during the ethanol infusion; P<0.001) as well as an increase in fractional sodium excretion (0.17 ± 0.04 to 0.28 ± 0.05 and 0.27 ± 0.05%; P<0.001). There was also a brief phosphaturia. These increases in electrolyte excretion had returned to control values by 20 min despite a further increase in the plasma ethanol concentration.3. The urinary excretion of potassium, calcium and magnesium was not altered nor was glomerular filtration rate or renal plasma flow.4. Ethanol at a mean concentration of 1.60 mmol/L did not alter the action of a maximal concentration of AVP (75 ng/kg) on water or electrolyte transport. However, the antidiuretic effect of a submaximal concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of 1.63 and 0.98 mmol/L.5. These studies suggest that the ethanol induced diuresis commonly ascribed to inhibition of AVP secretion may also be due to other intrarenal effects of ethanol, possibly acting within the proximal tubule. These results also confirm recent in vitro findings that while ethanol does not inhibit the action of a maximal concentration of AVP, it does modulate the effects of lower AVP concentrations.
DECREASED SENSITIVITY TO β‐ADRENERGIC STIMULATION OF THE VENTRICULAR CELLS ISOLATED FROM THE SPONTANEOUSLY HYPERTENSIVE RAT HEART
Authors: Habuchi Yoshizumi , Lu Ling‐Ling , Okamoto Shigetaka , Komori Toshiaki , Takahashi Hakuo , Morikawa Junichiro , Yoshimura Manabu 
Published: June 2007

Summary1. The stirnulatory effects of isoproterenol on the L‐type Ca2+ current (Ic.) were compared between the control (WKY) and hypertensive (SHR) rat heart cells, using the patch‐clamp method.2. The current density and the shape of the current‐voltage relationship for Ic. were not different between the two groups. However, the maximal percentage increase in response to isoproterenol was smaller in SHR (+ 91% in SHR and + 81% in WKY), and the ED50 was significantly higher in SHR (0.081 μmol/L in SHR and 0.020 μmol/L in WKY). IBMX, a potent phosphodiesterase inhibitor, significantly increased the isoproterenol‐stimulated Ica in SHR, but not in WKY. These results suggest an impaired CAMP production in SHR heart cells.
MOLECULAR MECHANISMS OF VASCULAR HYPERTROPHY IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Marche P. , Hérembert T. , Zhu D. L. 
Published: June 2007

Summary1. In primary hypertension, an abnormally high vascular resistance can be explained in terms of alterations in vessel wall structure. Arterial cell hypertrophy and/or hyperplasia have been implicated as playing a central role in the vascular abnormalities noted in spontaneously hypertensive rats (SHR). Cultured arterial cells appear therefore as attractive models for studying m vitro the mechanisms whereby cells originating from hypertensives exhibit hyperproliferation and/or hyper‐responsiveness.2. This review summarized our present knowledge on growth and related biochemical events of cultured SHR‐derived vascular smooth muscle cells or aortic adventitial fibroblasts, in response to various polypeptide growth factors and vasoactive agents.3. Exaggerated growth response to various mitogens in cultured SHR‐derived vascular cells has been well documented. However, the molecular mechanisms of abnormal growth in SHR remain unknown. This abnormality seems not to be a consequence of the alterations at the levels of receptors or of some key mitogenic events of early signalling pathways such as phospholipase C, protein kinase C and G‐proteins. Further studies should therefore focus on the more distal events related to cell growth.
ALTERATION IN THE RELEASE OF ENDOTHELIUM‐DERIVED RELAXING FACTORS BY α‐ADRENOCEPTOR STIMULATION IN THE AORTA OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Shimamura K. , Matsuda K. , Yamamoto K. , Sunano S. 
Published: June 2007

Summary1. Endothelium‐dependent relaxation by a‐adrenoceptor agonists was examined in the thoracic aorta from normoten‐sive Wistar‐Kyoto (WKY) rats and stroke‐prone spontaneously hypertensive rats (SHRSP).2. In ring preparations from both strains, noradrenaline‐induced contraction was increased by L‐nitro arginine (L‐NNA), a NO synthesis inhibitor.3. L‐NNA increased the contraction induced by phenyl‐ephrine, an α1‐adrenoceptor agonist. UK‐14304 and clonidine, α2‐adrenoceptor agonists, did not contract the preparations with intact endothelium. However, these agents contracted preparations when NO synthesis was inhibited.4. In a precontracted preparation, clonidine and UK‐14304 induced relaxations. The relaxations in SHRSP aorta were smaller than those in WKY aorta.5. These results indicate that a‐agonists release NO from endothelium in WKY and SHRSP aorta. The mechanism related to NO release by α2‐adrenoceptor agonist is impaired in SHRSP aorta.
GENE EXPRESSION OF VASCULAR NATRIURETIC PEPTIDE RECEPTOR IN THE AORTA OF HYPERTENSIVE RATS
Authors: Yoshimoto Takanobu , Naruse Mitsuhide , Naruse Kiyoko , Fujimaki Yasuko , Tanabe Akiyo , Muraki Takamura , Hagiwara Hiromi , Hirose Shigehisa , Demura Hiroshi 
Published: June 2007

Summary1. To elucidate the pathophysiologic role of vascular natriuretic peptide (NP) receptor in hypertension, we determined NP‐A and NP‐B receptor mRNA levels by means of ribonuclease protection assay in aorta of three types of hypertensive rats.2. The NP‐A receptor mRNA level was higher in stroke‐prone spontaneously hypertensive rats (SHR‐SP/Izm) and deoxycorticosterone acetate‐salt hypertensive rats than that in their respective control rats. On the contrary, the NP‐A receptor mRNA level was lower in NG‐nitro‐L‐arginine‐methyl ester (L‐NAME)‐induced hypertensive rats compared with that in the control.3. The NP‐B receptor mRNA level did not show any significant change in all three hypertensive rats compared with their respective controls.4. The present study suggests that high blood pressure is not the major factor regulating the NP receptor gene expression and also that the receptor subtype is independently regulated from each other.
EXPRESSION OF PROTEIN KINASE C GENE IN THE BRAIN AND HEART OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Gao Ping‐jin , Zhao Guang‐sheng , Yuan Xiao‐yuan , Zhao Han‐fang , Chen Feng , Chen Shi‐shu 
Published: June 2007

Summary1. The aim of this study was to investigate protein kinase C (PKC) gene expression in spontaneously hypertensive rats (SHR).2. Using the PKC oligodeoxyribonucleotide probes (γ, ε), we detected PKC isoforms gene expression in the heart and brain of 4 and 20 week old SHR with those of age‐matched Wistar‐Kyoto (WKY) rats by northern blot analysis.3. In the cerebral cortex, there were significantly increased levels of expression of the Ca2+‐dependent isoform PKC‐γ in 4 and 20 weeks SHR compared with that of WKY, while Ca2+‐independent isoform PKC‐ε did not differ between SHR and WKY.4. In ventricular myocytes, there was a significant expression of the Ca2+‐independent isoform PKC‐ε in 4 and 20 week old SHR compared with that of WKY, while Ca2+‐dependent isoform PKC‐γ could not be detected in the same extracts of SHR or WKY.5. We conclude that both of the Ca2+‐dependent and Ca2+‐independent PKC could be involved in the pathogenesis of SHR. Ca2+‐dependent PKC‐γ may be mainly involved in the modulation of blood pressure in the level of the central nervous system, while Ca2+‐independent PKC‐ε Could be related to the genetic myocardial hypertrophy.
ANIMAL MODELS OF VASCULAR DEMENTIA WITH EMPHASIS ON STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Saito Hideya , Togashi Hiroko , Yoshioka Mitsuhiro , Nakamura Nishio , Minami Masaru , Parvez Hasan 
Published: June 2007

Summary1. Two experimental models designed to reflect different aspects of vascular dementia (rats with cerebrovascular occlusion and rats with cerebral embolization) and stroke‐prone spontaneously hypertensive rats (SHRSP) have been evaluated. The focus was on SHRSP as a model for vascular dementia.2. Neuropathological data revealed that the cerebrovascular disorder in SHRSP was associated with lesions in their brains similar to those seen in typical human cases of multiple cerebral infarction.3. SHRSP that died from cerebral infarction exhibited behavioural changes, including increased activity and disrupted circadian rhythms, which might correspond to the state of delirium observed in patients with dementia.4. SHRSP displayed cognitive impairments in a step‐through passive avoidance task.5. When compared to age‐matched Wistar Kyoto (WKY) rats, both conscious and anaesthetized SHRSP had significantly decreased cerebral spinal fluid (CSF) levels of acetylcholine (ACh).6. These findings suggest that the SHRSP might serve as a suitable animal model for vascular dementia in humans caused by cerebrovascular lesions.
DISTINCTION OF ENDUTHELIAL CELL GROWTH AND FIBRINOLYTIC ACTIVITY BETWEEN WKY/Izm AND SHRSP/Izm IN VITRO
Authors: Ito Shigeru , Nara Yasuo , Yamori Yukio 
Published: June 2007

Summary1. In the present study, endothelial cells (EC) growth and fibrinolytic activity of WKY/Izm and SHRSP/Izm were investigated in vitro.2. EC were isolated from the thoracic aortas of WKY and SHRSP at the age of 8–9 weeks. Proliferative activities of EC were analysed with doubling time and DNA synthesis. Fibrinolytic activity was determined by tissue type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI‐1) activities in cultured medium.3. SHRSP‐EC growth rate was significantly greater than WKY‐EC growth rate in doubling time. In the assay for DNA synthesis, 5‐bromo‐2′‐deoxy uridine incorporation rate in SHRSP‐EC was significantly increased compared with that in WKY‐EC.4. The tPA activity in cultured medium of WKY‐EC was 2‐fold greater than that of SHRSP‐EC, while PAI‐1 activities were nearly equal in them.5. These physiological distinctions of EC of SHRSP/Izm from that of WKY/Izm with close genetic background could be contributory genetic factors to hypertension‐related vascular diseases in SHRSP.
HMG‐COA REDUCTASE INHIBITOR AFFECTS BLOOD PRESSURE AND VASCULAR REACTIVITY
Authors: Li N. , Sawamura M. , Nara Y. , Kizawa K. , Ikeda K. , Usui H. , Kurahasi K. , Yamori Y. 
Published: June 2007

Summary1. To investigate the effect of endogenous cholesterol synthesis on blood pressure and vascular response, a HMG CoA reductase inhibitor, pravastatin (1 or 10 mg/kg) was administered orally for 2 or 4 weeks to 8–13 week old spontaneously hypertensive rats (SHR/Izm) and normotensive Wistar‐Kyoto (WKY/Izm) rats.2. Blood pressure was significantly increased in the pravastatin‐treated groups of both strains, but the elevation was observed in WKY after a longer treatment than in SHR.3. After the thoracic aorta from 10–12 week old SHR and WKY was pretreated with pravastatin (10‐4 mol/L), the vascular response to norepinephrine was increased in pravastatin‐treated SHR aorta but not in the WKY aorta in both contractivity and sensitivity.4. These experiments suggest that the vascular response is affected by intracellular cholesterol synthesis pathway.
EFFECTS OF CHRONIC TREATMENT WITH CARVEDILOL ON ABNORMALITIES OF ENDOTHELIUM‐DEPENDENT RELAXATION AND STRUCTURE OF ENDOTHELIUM IN RESISTANCE ARTERIES OF SHRSP
Authors: Sasaki F. , Yamamoto K. , Shimamura K. , Shibutani T. , Hashimoto H. , Tanaka M. , Sunano S. 
Published: June 2007

Summary1. This study investigated the effects of chronic treatment with carvedilol, a β‐blocking agent with an α‐blocking activity, on blood pressure, endothelium‐dependent relaxation and the endothelial structure of the mesenteric resistance artery in stroke‐prone spontaneously hypertensive rats (SHRSP).2. Chronic treatment with carvedilol at a dose range of 30–120 mg/kg per day lowered systolic blood pressure of SHRSP from 234.9 ± 3.3 to 198.7 ± 3.1 mmHg at 16 weeks of age.3. Acetylcholine‐induced endothelium‐dependent relaxation was impaired in the mesenteric artery from SHRSP and high concentrations of acetylcholine produced contractions. The impairment of the relaxation was abolished in the presence of indomethacin. Carvedilol treatment improved the impairment in the preparation from SHRSP. The structural abnormality of endothelium was observed in the preparation from SHRSP. The abnormality could be prevented by the antihypertensive treatment.4. These results suggest that the impairment of endothelium‐dependent relaxation in the preparation from SHRSP is due to the corelease of an endothelium‐derived contracting factor which is considered to be a product of cyclo‐oxygenase pathway of arachidonic acid cascade and that the impairment can be prevented by the antihypertensive treatment with carvedilol.
SUPPRESSIVE EFFECTS OF BENIDIPINE ON THE DEVELOPMENT OF HYPERTENSION AND RENAL LESIONS IN SALT‐LOADED STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Nito M. , Sato H. , Hara T. , Karasawa A. , Yamada K. , Ohta Y. 
Published: June 2007

Summary1. The effects of benidipine hydrochloride (benidipine), a long‐acting dihydropyridine calcium antagonist, on the development of hypertension and renal lesions were examined in stroke‐prone spontaneously hypertensive rats (SHRSP).2. SHRSP were fed with 8% NaCl diet for 3 weeks from 13 weeks of age, and benidipine (1 or 3 mg/kg per day) was orally administered during the same period.3. The high salt diet accelerated an increase in urinary excretions of total protein and albumin, and caused marked arteriole, glomerular and tubular lesions in the kidney.4. Benidipine significantly inhibited these changes, and also suppressed the elevation of blood pressure in salt‐loaded SHRSP.5. These results reveal that benidipine has protective effects against the development of hypertension and the progression of renal lesions induced by the high salt diet in SHRSP.
HYPOTENSIVE EFFECTS OF A NEW TRANSDERMAL DELIVERY SYSTEM FOR CLONIDINE (M‐5041T) IN SPONTANEOUSLY AND RENAL HYPERTENSIVE RATS
Authors: Ishii R. , Naruse T. , Tagawa T. , Ishida T. , Namba K. 
Published: June 2007

Summary1. Antihypertensive effects of a new transdermal delivery system for clonidine (clonidine tape; M‐50417) were investigated in spontaneously hypertensive rats (SHR), 2‐kidney, 1‐clip renal hypertensive rats (RHR) and deoxycorticosterone acetate/salt (DOCA/Salt) hypertensive rats.2. M‐5041T (0.5–4.5 mg/kg) elicited long‐lasting hypotensive effects and bradycardia in a dose‐dependent manner during 24 h patching in three hypertensive models compared with oral clonidine (100 μg/kg).3. The most hypotensive effect of M‐5041T was observed in DOCA/salt hypertensive rats.4. Co‐administration of M‐5041T with either trichloromethiazide (1 mg/kg, orally) or nifedipine (3 mg/kg, orally) at each dose without hypotensive effects per se induced significant hypotension in SHR.5. Repeated administrations of M‐5041T (1.5 mg/kg per day) for a consecutive 7 days produced significant hypotensive effects at postpatching 6 h, and recovered a postpatching 24 h in SHR.6. Repetitive M‐5041T administrations displayed no tolerance on the hypotensive effects and were devoid of any withdrawal syndrome.7. These findings suggest that M‐5041T may serve as an efficiently useful antihypertensive transdermal delivery system in humans.
NORADRENERGIC HYPERINNERVATION IN THE CAVAL VEIN OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Tabei Ryo , Kondo Mari , Terada Miho , Miyazaki Tatsuhiko , Watanabe Yukihiko , Shimizu Daisaburou , Yamamoto Ichirou 
Published: June 2007

Summary1. The distribution of fluorescent noradrenergic (NA) nerve fibres in the caval vein, which originate from the coeliac ganglion, was examined by glyoxylic acid method in stroke‐prone spontaneously hypertensive rats (SHRSP) aged 10, 30, 60, 90 and 180 days. The results were compared with those in age‐matched normotensive Wistar Kyoto (WKY) rats.2. The distribution pattern of NA nerve fibres in the caval vein in both strains changed from a meshwork pattern at 10 days of age to a wavelike line arrangement after 30 days of age.3. The densities of NA fibres of the caval veins in SHRSP were significantly higher (P < 0.01, Student's t‐test, 6 d.f.) than those of WKY at all ages examined. The difference in NA fibre density between SHRSP and WKY showed double peaks at 10 and 90 days of age.4. The present study suggests that hyperinnervation of the caval vein based on the hyperfunction of the coeliac ganglion is an important factor in the development of hypertension and also may participate in increasing cardiac output because the heart of SHR causes marked hypertrophy from 90 days of age.
NORADRENERGIC HYPERINNERVATION IN THE HEART OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Kondo Mari , Terada Miho , Fujiwara Takashi , Arita Norimasa , Yano Akemi , Tabei Ryo 
Published: June 2007

Summary1. Noradrenergic (NA) nerve fibre distribution was investigated in the epicardium and myocardium of the heart in stroke‐prone spontaneously hypertensive rats (SHRSP) and was compared to that in normotensive Wistar‐Kyoto (WKY) rats. Fluorescent NA nerve fibres in the left and right epicardium of both strains aged 10, 30, 60, 90 and 180 days, and in the myocardium of left and right ventricles and the ventricular septum of both strains aged 30, 90 and 180 days were examined by the glyoxylic acid method. The distribution densities of NA nerve fibres were measured by quantitative image analysis.2. The distribution pattern of NA nerve fibres in the epicardium of both strains showed a constant meshwork pattern throughout the entire examination period.3. In the myocardium, NA nerve fibres were distributed irregularly between myocytes of both strains in all ages examined.4. The densities of NA nerve fibres in the epicardium of SHRSP were significantly higher (P < 0.01 and 0.05; Student's t‐test, 6 d.f.) than those of WKY at all ages examined except left epicardium at 90 days of age.5. The densities in the right myocardium in 30 and 90 day old SHRSP were significantly higher (P < 0.05; Student's t‐test, 6 d.f.) than those of WKY.6. NA hyperinnervation in the epicardium and the myocardium of SHRSP may be assumed to be caused by the hyperfunction of the stellate ganglia which innervate the heart and may give rise to hypertrophy of the heart in SHRSP by a trophic effect of NA nerve fibre.
AGE‐RELATED CHANGES IN CEREBRAL AND PERIPHERAL MONOAMINE CONTENTS IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Uchida T. , Nishimura Y. , Suzuki A. 
Published: June 2007

Summary1. We examined monoamine contents in various regions of the brain and catecholamine contents in the heart and the adrenal gland of stroke‐prone spontaneously hypertensive rats (SHRSP) and Wistar‐Kyoto (WKY) rats aged 1.5, 3 and 6 months.2. The noradrenaline (NA) content and the 5‐hydroxytryptamine (5‐HT) content in the brainstem were larger in 1.5 month old SHRSP than in the age‐matched WKY. In addition, at age 6 months the brainstem 5‐HT content was higher in SHRSP than in WKY.3. The NA and 5‐HT contents in basal ganglia, thalamus, hypothalamus, septum and anterior and lateral cerebral cortex showed no significant difference between SHRSP and WKY at any age.4. The dopamine (DA) contents in all brain regions examined did not differ between WKY and SHRSP at any age.5. The NA contents in left and right ventricles were larger in 3 month old SHRSP than in the age‐matched WKY, but were lower in 6 month old SHRSP than in the age‐matched WKY. The cardiac DA contents did not differ between the two rat strains of any age.6. The adrenal NA and adrenaline (A) contents in 6 month old SHRSP were significantly larger than those in the corresponding WKY.7. These findings suggest that the increased NA and 5‐HT contents in the brainstem may be related to the onset of hypertension, and that the altered cardiac NA contents and adrenal NA and A contents change as a result of the onset or persistence of hypertension.
ROLE OF RENAL DOPAMINERGIC ACTIVITY ON RENAL SODIUM‐WATER METABOLISM IN CONGESTIVE HEART FAILURE
Authors: Hayashi Manabu , Shimamoto Kazuaki , Tsuchihashi Kazufumi , Ishiguro Toshiya , Torii Taka‐aki , Sawai Niroh , Mukai Hiroya , Iimura Osamu 
Published: June 2007

SUMMARY1. The role of the renal dopaminergic system in water‐sodium metabolism in heart failure remains unclear.2. In this study, the urinary free dopamine excretion (uDA), delivery of l‐dopa X creatinine clearance (Cer)), and the production of dopamine in the kidney [uDA/(plasma l‐dopa x Cer)] were investigated in patients with congestive herat failure (n= 30) and in normal controls (n = 12). In both groups, endogenous Ccr, urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma noradrenaline concentration (pNA) and plasma l‐dopa and dopamine production in the kidney showed successively lower values in congestive heart failure with progression in NYHA functional class.4. UNaV (r = 0.48, P < 0.05) and Cer (r = 0.539, P < 0.01) positively correlated with uDA. Linear correlations were found between left ventricular ejection fraction and uDA (r = 0.574, P < 0.01), pNA)r = ‐0.495, P < 0.01) or plasma <sc>l‐dopa (r = 0.423, P < 0.05).5. From these findings, it was suggested that (i) uDA was clearly suppressed in patients with CHF, and (ii) the possible mechanisms of its suppression might be due to decrease of delivery of l‐dopa into the proximal tubulles and suppressed production of dopamine from l‐dopa in the kidney.