bluuebunny/crossref_metadata_2025_split huggingface dataset:
LONG‐TERM EFFECTS OF TREATMENT WITH ENALAPRIL ON THE STRUCTURE OF MESENTERIC RESISTANCE ARTERIES IN NEW ZEALAND GENETICALLY HYPERTENSIVE RATS
Authors: Ledingham Janet M. , Laverty R. 
Published: June 2007

Summary1. New Zealand genetically hypertensive (GH) rats were treated with enalapril (20mg/kg per day in drinking fluids) from age 4–10 weeks; one group (GHex‐enal) was then taken off enalapril and followed for 6 more weeks to see if the drug‐induced changes in blood pressure (BP) and structure of mesenteric resistance arteries (MRA) were long lasting once the enalapril was withdrawn. Control groups consisted of untreated GH and their normotensive (N) control strain.2. Tail‐cuff BP in GH treated rats fell significantly to N BP levels during treatment. On cessation of treatment BP rose rapidly. At age 16 weeks BP, although at a hypertensive level (mean ± s.e.m., GHex‐enal, 210.8 ± 4.7 mmHg), was still significantly below the GH controls (230 ± 6.9, P < 0.05), but above the N control group (137 ± 3, P < 0.0001).3. Left ventricular (LV) mass in GH rats was reduced by enalapril to that in N rats; at the end of the subsequent period without treatment it was still significantly lower than the GH control group, but also significantly above the N group (GHexenal, 255 ± 6; GH 306 ± 11; N 179 ± 3, mg/100 g bodyweight).4. The large changes in media, lumen and media/lumen ratio seen after 6 weeks of treatment were not sustained over the subsequent non‐treatment period. However, values in the GHex‐enal group at 16 weeks were closer to those in the N16 control group.5. The persisting effects on smooth muscle (SM) cell density and SM fraction of the media contributed to an increase in SM cell volume which was significantly greater than the N16 group (P < 0.01). The number of layers of SM in the media was less than in the GH16 control group and not different from the N16 controls.6. In GH rats the effect of ACEI on BP, LV mass and MRA structure is relatively longlasting once treatment is withdrawn.
ENALAPRIL IMPROVES GLUCOSE TOLERANCE IN TWO RAT MODELS: A NEW HYPERTENSIVE DIABETIC STRAIN AND A FRUCTOSE‐INDUCED HYPERINSULINAEMIC RAT
Authors: Rosenthal T. , Erlich Y. , Rosenmann E. , Grossman E. , Cohen A. 
Published: June 2007

Summary1. The present study was undertaken to examine the effect of the angiotensin converting enzyme (ACE) inhibitor, enalapril, on blood pressure and spontaneous blood glucose levels in two rat models: our new diabetic hypertensive rat in which genetic hypertension and diabetes develop following cross‐breeding of Cohen diabetic rat (CDR) and spontaneous hypertensive rats (SHR); and a rat in which hypertension, hyperinsulinaemia and hyperlipidaemia were induced by fructose diet.2. The new strain of animal was fed the usual copper‐poor sucrose diet, and for 4 weeks received enalapril. The fructose‐induced hyperinsulinaemic animals were fed a fructose‐enriched diet for 3 weeks, and enalapril 20 mg per kg per day was added to the drinking water for 2 more weeks.3. The new strain of diabetic‐hypertensive rats that received enalapril showed a significant decrease in blood pressure level. The fructose‐fed animals showed a fall in insulin and blood pressure following the introduction of enalapril to their diet.4. The present study confirms the advantage of the ACE inhibitor enalapril in improving the metabolic parameters of hypertensive diabetic rats, including insulin sensitivity.
EFFECT OF AN ANGIOTENSIN II RECEPTOR ANTAGONIST, TCV‐116, ON NEOINTIMAL FORMATION FOLLOWING BALLOON INJURY IN THE SHR CAROTID ARTERY
Authors: Kino Hirofumi , Hama Junkichi , Takenaka Toshihiko , Sugimura Keiichi , Kamoi Kouji , Shimada Seijiro , Yamamoto Yoshihiro , Nagata Shuzo , Kai Tatsuya , Horiuchi Masatsugu , Katori Ryo 
Published: June 2007

Summary1. In the present study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV‐116, on carotid neointimal formation after balloon injury in SHR and WKY rats.2. Oral administration of TCV‐116 at a dose of 10mg/kg per day reduced not only systolic blood pressure but also neointimal formation after carotid balloon injury. TCV‐116 also suppressed cardiac hypertrophy. An angiotensin‐converting enzyme inhibitor, lisinopril (20mg/kg per day), had a similar effect to that of TCV‐116.3. In the WKY experiment, both TCV‐116 and lisinopril suppressed neointimal formation as well as systolic blood pressure, but did not suppress cardiac hypertrophy.4. Although SHR showed markedly enhanced neointimal formation after balloon injury compared with age‐matched WKY rat, both TCV‐116 and lisinopril showed similar sup‐pressive effects on neointimal formation in both SHR and WKY rats.5. These results confirm the important role of angiotensin II in neointimal formation following balloon injury. Further studies are needed to clarify the mechanism of the difference between SHR and WKY rats in the response of vascular smooth muscle cells.
CARDIOVASCULAR AND RENAL PROTECTIVE EFFECTS OF LOSARTAN IN SPONTANEOUSLY HYPERTENSIVE RATS WITH DIABETES MELLITUS
Authors: Kohzuki Masahiro , Yasujima Minoru , Liu Ping Fu , Obara Katsuya , Kanazawa Masayuki , Yoshida Kazunori , Saito Takao , Sato Tokutaro , Abe Keishi 
Published: June 2007

Summary1. Cardiovascular and renal benefits of a specific angiotensin II (AII) receptor antagonist, losartan (LOS), were assessed in diabetic rats with renal impairment.2. Uninephrectomized SHR made diabetic by streptozotocin administration were given LOS (5 mg/kg per day, i.p.) alone, captopril (CAP) (50 mg/kg per day, i.p.) alone, or a combination of CAP and LOS via osmotic minipumps for 8 weeks.3. Both CAP alone and LOS alone completely blocked the development of hypertension in diabetic SHR in the same manner. CAP + LOS did not enhance the antihypertensive effects of LOS alone or CAP alone.4. CAP+LOS, LOS alone and CAP alone significantly decreased urinary protein excretion and serum creatinine to the same extent.5. These results indicate that both LOS and CAP exert antihypertensive and renoprotective effects in this model: these actions are mainly through inhibition of AII production.
RENIN‐ANGIOTENSIN SYSTEM IN THE ANTIHYPERTENSIVE EFFECT OF ISOTEOLINE IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Markov M. , Higashino H. , Suzuki A. 
Published: June 2007

Summary1. The aim of the present study was to examine the effects of isoteoline (IST), a new tetrahydroaporphine derivative, on the blood pressure and some of the components of renin‐angiotensin‐aldosterone system (RAAS) in spontaneously hypertensive rats (SHR).2. After long‐term treatment (14 days, 3 times daily) in a dose of 1 mg/kg orally and intraperitoneally, IST induced a significant decrease of the systolic blood pressure (SBP) in SHR (from 192 ± 2 to 155 ± 5 mgHg).3. At the same time, IST induced a significant decrease of the levels of plasma renin activity (PRA) and aldosterone (ALD) and manifested a trend to increase the sodium plasma level.4. These results indicate that IST after chronic long‐term treatment induced a marked antihypertensive effect and inhibited the components of RAAS in SHR. Apparently, the long‐lasting antihypertensive effect of IST in SHR was mediated and realized in part by inhibition of the components of RAAS.
EVOLUTION OF DOSE‐RELATED CARDIOVASCULAR RESPONSES TO L‐GLUTAMATE MICROINJECTED INTO THE NUCLEUS TRACTUS SOLITARII AFTER REMOVAL OF THE NODOSE GANGLION IN RAT
Authors: Talman W. T. , Colombari E. 
Published: June 2007

Summary1. In this study, we sought to determine if sensitivity to dose‐related changes in arterial pressure (AP) and heart rate (HR) elicited by microinjection of L‐glutamate (L‐GLU) into the nucleus tractus solitarii (NTS) evolves after deafferentation in adult male Sprague‐Dawley rats.2. Twelve rats served as unoperated controls; and eight were studied 5 days, eleven 10 days and nine 15 days after ganglionectomy. Each rat was anaesthetized (halothane 1.5–2.096) and cannulated for recording AP and HR. Vehicle or L‐GLU (3, 30, 75, 150, 300 and 1500 pmole/50 nL) was microinjected into the right and left NTS. Injection sites were confirmed histologically.3. In control animals and in animals 5 days and 15 days after ganglionectomy, the lowest dose of L‐GLU that produced a significant fall of AP was 30 pmole. The threshold dose with injections on the lesioned side 10 days after ganglionectomy was 3 pmole. In rats studied at 10 days, but not in control, 5 or 15 day rats, dose‐related responses for injections made on the left were shifted significantly to the left of those made on the right (P < 0.05).4. In control, 5 and 15 day rats there were no significant differences between dose‐related responses elicited from right and left NTS. Responses of HR did not differ between groups of animals or sides of injection.5. These results suggest that supersensitivity to L‐GLU evolves after nodose ganglionectomy and support a role for L‐GLU as a transmitter of cardiovascular afferents in the NTS.
ACETYLCHOLINE RELEASE IN THE ROSTRAL VENTROLATERAL MEDULLA OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Kubo Takao , Ishizuka Takanobu , Asari Tetsuya , Fukumori Ryuji 
Published: June 2007

Summary1. Central acetylcholine (ACh) has been implicated in the pathogenesis of experimental hypertension and the rostral ventrolateral medulla (RVLM) is an important area for cardiovascular regulation. The purpose of this study was to determine whether cholinergic neurotransmission in the RVLM is altered in spontaneously hypertensive rats (SHR).2. Experiments were performed on male SHR (12–16 weeks) and age‐matched Wistar‐Kyoto rats (WKY). The rats anaesthetized with pentobarbital were placed in a stereotaxic apparatus. For determining the release of ACh in the RVLM, a dialysis probe was introduced into the RVLM.3. An RVLM microinjection of cholinergic agents elicited an increase in blood pressure. The pressor response to physostigmine was greater in SHR than that of WKY whereas there was no difference in the pressor response to ACh or carbachol between SHR and WKY.4. The release of ACh in the RVLM was greater in SHR than that of WKY. Physostigmine (0.5 mg/kg, i.p.) produced increases in medulla ACh contents. The increase in ACh content of the rostroventral medulla including the RVLM was greater in SHR than that of WKY whereas there was no difference in ACh contents of the other three parts of the medulla oblongata between SHR and WKY.5. Depressor responses to scopolamine injected bilaterally into the RVLM were greater in SHR than those of WKY.6. These results suggest that ACh release is enhanced specifically in the RVLM of SHR. It appears that this enhanced release of ACh in the RVLM of SHR contributes to the maintenance of hypertension in SHR.
ALTERED BASAL RELEASE AND PRESSOR EFFECT OF L‐DOPA IN THE ROSTRAL VENTROLATERAL MEDULLA OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Yue Jin‐Liang , Miyamae Takeaki , Ueda Hiroshi , Misu Yoshimi 
Published: June 2007

Summary1. Transmitter‐like L‐DOPA functions as a tonic to produce postsynaptic cardiopressor responses in the rostral ventrolateral medulla (RVLM) of rats. We attempted to clarify whether a transmitter‐like L‐DOPA system is altered in the RVLM of spontaneously hypertensive rats (SHR) to maintain the hypertension.2. By microdialysis of left RVLM area, the basal L‐DOPA release was higher in SHR than in Wistar‐Kyoto (WKY) rats. This release was partially inhibited by tetrodotoxin (TTX, 1 μmol/L) to a similar degree in both strains. TTX‐sensitive L‐DOPA release was higher in SHR than in WKY.3. L‐DOPA (10–600 ng) and L‐glutamate (10–300 ng) microinjected into left RVLM produced dose‐dependent hypertension and tachycardia. Pressor but not tachycardiac responses to L‐DOPA at lower doses were slightly greater in SHR than in WKY, whereas no difference to L‐glutamate was observed in either strain.4. In RVLM regions, there was no difference of tyrosine hydroxylase activity in SHR or WKY; however, L‐aromatic amino acid decarboxylase activity was lower in SHR than in WKY.5. Enhanced presynaptic neuronal L‐DOPA release, including a decrease in decarboxylation and sensitization of postsynaptic pressor sites to L‐DOPA in RVLM, may be involved in the maintenance of hypertension in SHR.
SYNERGISTIC EFFECTS OF BAY K 8644 AND BRADYKININ ON NOREPINEPHRINE RELEASE IN THE HYPOTHALAMUS OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Tsuda Kazushi , Tsuda Seiko , Nishio Ichiro , Masuyama Yoshiaki , Goldstein Menek 
Published: June 2007

Summary1. In the present study, we examined the effects of Bay K 8644, a dihydropyridine (DHP)‐sensitive Ca2+ channel agonist, and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats (SHR).2. In the preliminary studies using Sprague‐Dawley rats, Bay K 8644 by itself had no significant effects on the stimulation‐evoked [3H]‐norepinephrine release from hypothalamic slices. Bradykinin increased the stimulation‐evoked [3H]‐nor‐epinephrine release in a dose‐related fashion. The facilitatory effects of bradykinin on norepinephrine release were potentiated by Bay K 8644.3. In SHR, Bay K 8644 significantly increased the stimulation‐evoked norepinephrine release from hypothalamic slices. However, exposure of slices to Bay K 8644 caused no significant effects on norepinephrine release in Wistar‐Kyoto (WKY) rats. The effects of Bay K 8644 in combination with bradykinin on the stimulation‐evoked norepinephrine release were also greater in SHR than in WKY rats.4. These results demonstrate that Bay K 8644 significantly potentiated the facilitatory effects of bradykinin on norepinephrine release in rat hypothalamus. The finding indicates a possible interaction of bradykinin with DHP‐sensitive Ca2+ channels in the central nervous system. Furthermore, the pronounced effects of Bay K 8644 and bradykinin in SHR suggest that bradykinin‐related Ca2+ channels might have a role in the regulation of norepinephrine release in the hypothalamus of SHR.
ALTERATION OF BARORECEPTOR AND CHEMORECEPTOR REFLEXES IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Ohta H. , Talman W. T. 
Published: June 2007

Summary1. Electrical stimulation of the aortic depressor nerve elicited depressor and bradycardiac responses in both spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats, but in spontaneously breathing animals responses were weaker in SHR than in WKY.2. Responses did not significantly differ in artificially ventilated animals except that high stimulation intensity elicited significantly greater bradycardiac responses in WKY. A decrease in ventilatory rate occurred in both strains.3. Electrical stimulation of the carotid sinus nerve (CSN) elicited an initial pressor response followed by a depressor response with a minimal change in heart rate in either strain. The pressor response in SHR was greater than in WKY. Depressor responses in SHR were weaker than those in WKY with or without artificial ventilation. CSN stimulation increased ventilatory rate in both strains but the frequency‐related responses differed at higher stimulation intensity.4. These results suggest that there are alterations in the function of central or afferent components of chemoreceptor and baroreceptor reflexes in SHR in addition to previously described structural changes at the level of peripheral sensory receptors.
BARORECEPTOR FUNCTION IS RESTORED BY ANTIHYPERTENSIVE THERAPY THROUGH LOWERING OF BLOOD PRESSURE IN ADULT SHR
Authors: Ichikawa Masashi , Suzuki Hiromichi , Kumagai Kazuhiro , Ryuzaki Munekazu , Kumagai Hiroo , Nishizawa Masahiko , Saruta Takao 
Published: June 2007

Summary1. We investigated the effects of antihypertensive treatment (8 weeks) with four different agents (trichlormethiazide, atenolol, nicardipine and enalapril) on baroreceptor function in 28 week old spontaneously hypertensive rats (SHR) to measure aortic depressor nerve (ADN) activity.2. Threshold pressure (P th) of ADN activity was elevated and the gain sensitivity of the pressure–‐activity curve, as determined by the maximum gain (Gmax) of a logistic function curve, was depressed in untreated SHR compared to those in untreated Wistar‐Kyoto (WKY) rats.3. Treatment with the four agents similarly reduced blood pressure in SHR. Each of the four agents induced a decrease in Pth and an increase in Gmax to a similar extent in SHR.4. These findings suggest that antihypertensive therapy in chronic hypertension augments baroreceptor function through the lowering of blood pressure but not through specific pharmacological actions.
ROLE OF AN ENDOGENOUS MONOAMINE OXIDASE INHIBITOR, ISATIN, IN SHRSP BRAIN
Authors: Hamaue N. , Endo T. , Hirafuji M. , Yamazaki N. , Togashi H. , Saito H. , Minami M. 
Published: June 2007

Summary1. The acute effects of isatin, an endogenous monoamine oxidase (MAO) inhibitor, on norepinephrine (NE) and serotonin (5‐HT) concentrations in the brain of stroke‐prone spontaneously hypertensive rats (SHRSP) and Wistar‐Kyoto rats (WKY) were determined in order to elucidate its pathophysiological role.2. Isatin was identified in purified extracts of SHRSP brain.3. A single dose of isatin significantly increased NE concentration in the cerebral cortex of WKY. Isatin also significantly increased 5‐HT concentration in WKY brains.4. After isatin administration NE and 5‐HT levels in the SHRSP brain did not differ from those in WKY.5. These data suggest that isatin, an endogenous MAO inhibitor, presents in the SHRSP brain and maintains high blood pressure.
EFFECT OF METHOXAMINE ON NORADRENALINE RELEASE IN THE CAUDAL ARTERY OF HYPERTENSIVE RATS
Authors: Shinozuka Kazumasa , Kunitomo Masaru , Bjur Richard A. , Westfall David P. , Hattori Keisuke 
Published: June 2007

Summary1. The effect of methoxamine, an α1‐adrenoceptor agonist, on the overflow of endogenous noradrenaline (NA) was examined in the electrically field stimulated (EFS) caudal artery obtained from Wistar rats, Wistar‐Kyoto rats (WKY) and age‐matched spontaneously hypertensive rats (SHR).2. Methoxamine inhibited the EFS‐evoked release of endogenous NA in the arteries from Wistar rats and WKY, but not in the arteries of SHR. 2‐chloroadenosine, a purinoceptor agonist, also inhibited the NA release in the arteries from normotensive rats but not in the arteries of SHR.3. The inhibitory effect of methoxamine was blocked by adenosine deaminase and potentiated by adenosine uptake inhibitor, dipyridamole.4. Methoxamine caused the release of adenine nucleotides and adenosine from the caudal arteries of WKY and SHR.5. These suggest that the inhibitory effect of methoxamine on NA release is mediated by endogenous adenyl purines and that the failure of methoxamine to inhibit NA release in the caudal artery of SHR is due to a dysfunction of the pre‐junctional purinoceptors on sympathetic nerve terminals.
α1‐ADRENOCEPTOR SUBTYPES MEDIATING THE CONTRACTION OF ARTERIES IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Fujimoto S. , Sumi‐Fujimoto K. 
Published: June 2007

Summary1. This study was undertaken to determine which (α1‐adrenoceptor (AR) subtypes were involved in the activation of the femoral artery and the aorta by norepinephrine (NE) in spontaneously hypertensive rats (SHR).2. Negative log EC50 values and maximum responses of NE‐induced contraction of the SHR femoral artery were unchanged and increased, respectively, compared with those of Wistar‐Kyoto (WKY) rats.3. Contractile responses of the SHR aortas to NE were similar to those of the normotensive tissues.4. Schild plot data for cut‐AR antagonists indicated that α1‐AR in the aorta were predominantly α1H subtype. In the femoral artery, because Schild plots for bunazosin had slopes of less than 1.0, there were α1H (or α1C) and α1L subtypes.5. The α1‐AR subtype in the aorta was essentially identical to the α1H subtype in the femoral artery. α1‐AR subtypes mediating contraction in the SHR blood vessels were identical to those in the WKY tissues.
DOPAMINE‐INDUCED RELAXATION IN ISOLATED INTRARENAL ARTERIES FROM ADULT STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Gao Y. J. , Nishimura Y. , Suzuki A. 
Published: June 2007

Summary1. The relaxant effects of dopamine (DA) on the intrarenal arteries obtained from 6 month old stroke‐prone spontaneously hypertensive rats (SHRSP) and age‐matched Wistar‐Kyoto (WKY) rats were pharmacologically investigated in vitro.2. DA (10−7−3 × 10−5 mol/L) produced endothelium‐independent relaxation on the arterial rings which had been incubated with phenoxybenzamine (2 × 10−6 mol/L) and precontracted with KCI.3. DA‐induced relaxation was greater in the arterial rings from SHRSP than in those from WKY. SKF 38393 (10−8−10−6 mol/L) partially mimicked DA‐produced relaxation in both groups. SCH 23390 dose‐dependently inhibited DA‐induced relaxation with pD′2 value of 9.33 for SHRSP and of 9.26 for WKY.4. There were no significant differences between SHRSP and WKY in the relaxation caused by forskolin, dibutyryl cyclic AMP, or 3‐isobutyl‐1‐methylxanthine.5. These results suggested that DA1 receptor‐mediated relaxation was increased in the intrarenal arteries from SHRSP, and this increase might not be associated with altered vasodilation mediated by cyclic AMP.
ENHANCED CONTRACTILE RESPONSES MEDIATED BY DIFFERENT 5‐HT RECEPTOR SUBTYPES IN BASILAR ARTERIES, SUPERIOR MESENTERIC ARTERIES AND THORACIC AORTAS FROM STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Nishimura Y. , Suzuki A. 
Published: June 2007

Summary1. The contractile effects of 5‐hydroxytryptamine (5‐HT) in isolated ring preparations of basilar arteries (BA), thoracic aortas (TA) and superior mesenteric arteries (SMA) from stroke‐prone spontaneously hypertensive rats (SHRSP) and Wistar‐Kyoto (WKY) rats were investigated pharmacologically.2. The pD2 values (expressed as a negative logarithm of of EC50) for 5‐HT in BA of SHRSP were greater than those of WKY. Increased pD2 values for 5‐HT were also found in SMA and TA of SHRSP when compared to WKY.3. Ketanserin (a 5‐HT2 antagonist) produced a biphasic displacement of the concentration‐response curves for 5‐HT in BA of WKY and SHRSP but elicited a parallel rightward shift of the 5‐HT curve in SMA and TA of the two groups.4. 5‐CT (a 5‐HT1 agonist)‐induced contractions and their pD2 values in the presence of ketanserin were larger in BA of SHRSP than in those of WKY, while 5‐CT did not contract SMA or TA in either group.5. No significant difference was found in the contractile response induced by α‐methyl‐5‐HT (a 5‐HT2 agonist) in BA from SHRSP and WKY, while the pD2 values for α‐methyl‐5‐HT were increased in SMA and TA from SHRSP when compared to WKY.6. These results suggest that the hyperresponsiveness to 5‐HT found in SHRSP arteries may be mediated by different 5‐HT receptor subtypes, that is, by 5‐HT1 in BA and by 5‐HT2 in SMA and TA.
AN EXPERIMENTAL MODEL OF MIGRAINE WITH AURA: CORTICAL HYPOPERFUSION FOLLOWING SPREADING DEPRESSION IN THE AWAKE AND FREELY MOVING RAT
Authors: Shimazawa Masamitsu , Hara Hideaki 
Published: June 2007

SUMMARY1. Cortical spreading depression (CSD) was induced by direct current stimulation of the lateral frontal cortex in awake and freely moving rats.2. Regional cerebral blood flow (rCBF) was continuously measured by a laser Doppler flowmeter using an acrylic cup which was chronically fixed on the surface of the cerebral cortex. Under the resting condition rCBF remained constant throughout the observation period and showed a high reproducibility.3. rCBF increased to approximately 190% of control values during 1‐3 min after CSD, and decreased to approximately 80% of control values, before returning to normal values 60 min after CSD.4. These results are consistent with those found in anesthetized animals. This is the first study which has continuously monitored cortical hypoperfusion after CSD in awake and freely moving rats. The model is a useful system for studying migraine with aura.