bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF FELODIPINE ON BLOOD PRESSURE, BODY SODIUM, PLASMA RENIN ACTIVITY AND PLASMA ALDOSTERONE IN HYPERTENSIVE AND NORMO‐TENSIVE RATS
Authors: Ledingham Janet M. , Hamada M. , Simpson F. O. 
Published: June 2007

Summary1. To explore its effect on blood pressure (BP) in relation to body sodium (Na), felodipine was given to New Zealand genetically hypertensive (GH) and normotensive (N) rats and to Japanese SHR and WKY rats, prepared for repeated measurements of body sodium (Na) by a whole body counting technique (22Na) using an Na‐free pelleted diet and 22Na‐NaCl fluid as the sole source of Na, with water also available. The drug was added to the food before pelleting pellets, 0.5 mg/g food.2. Felodipine reduced BP in each strain; this effect was as great on normal Na intake as when on a zero Na intake. Felodipine caused an increase in plasma renin activity in each strain but the increase reached significant levels only in GH, SHR and WKY. Plasma aldosterone was decreased by treatment in GH and N and increased in SHR and WKY.3. In rats on a zero Na intake (water sole drinking fluid), felodipine caused no fall in body Na (i.e. no natriuretic effect was detectable) except in WKY. When saline was freely available, felodipine tended to stimulate saline intake and was associated with an increase in body Na in all strains except SHR; body Na was high in SHR even in the absence of felodipine and did not increase further with felodipine treatment. Felodipine slightly speeded up the excretion of an Na load in rats on an ample NaCl intake (choice of 0.5%22Na‐NaCl and water) but this may have been due, in part, to the treated rats having taken, by choice, a greater intake of saline in the pre‐load period.4. In this study, felodipine reduced BP and stimulated PRA and salt appetite. Its effects on Na handling varied to some extent between the strains; there was no consistent natriuretic effect, but rather some evidence of Na retention.
EFFECT OF FELODIPINE TREATMENT AND WITHDRAWAL ON BLOOD PRESSURE AND CARDIOVASCULAR STRUCTURE IN NEW ZEALAND GENETICALLY HYPERTENSIVE RATS
Authors: Ledingham J. M. , Phelan E. L. , Cross M. A. , Laverty R. 
Published: June 2007

Summary1. Four groups of New Zealand genetically hypertensive (GH) rats were treated with felodipine as follows: (A) from ages 4–12 weeks; (B) 4–20 weeks; (C) 4–12 weeks then withdrawn from felodipine till age 20 weeks; and (D) 12–20 weeks.2. Effects on blood pressure (BP), left ventricular (LV) weight and the structure of myograph‐mounted mesenteric resistance arteries (MRA) were measured.3. BP was about 170 mmHg in 4 week old GH rats and did not change substantially from this value in groups A and B but rose to over 230 mmHg in untreated controls. In rats of group D, started on felodipine at 12 weeks, BP fell rapidly and was 173 mmHg at 20 weeks. On withdrawal of felodipine at 12 weeks (group C) BP rose rapidly and exceeded control levels at 20 weeks.4. LV mass was significantly lower (P < 0.001) in all groups (A, B and D) killed while on felodipine but rose to control levels in the rats taken off felodipine.5. In the four treated groups there were no significant changes in MRA structure (lumen diameter, medial thickness, media/lumen ratio and volume of medial tissue) as measured on the myograph.6. Felodipine induces substantial falls in BP in GH rats which are sufficient to prevent cardiac hypertrophy but do not alter MRA structure. Resistance artery structure in GH rats does not seem to relate to the level of hypertension, and may therefore not have a necessary role in the pathogenesis of this hypertensive strain.
PROTECTIVE EFFECT OF NICARDIPINE TREATMENT ON CEREBROVASCULAR MICRO ANATOMICAL CHANGES IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Amenta Francesco , Fenante Fabio , Ricci Alberto , Sabbatini Maurizio 
Published: June 2007

Summary1. The effect of long‐term treatment with the dihydropyridine Ca2+ antagonist, nicardipine, on the morphology of different sized pial arteries was assessed in spontaneously hypertensive rats (SHR) using histological techniques associated with image analysis.2. In control 20 week old SHR blood pressure values, the thickness of the tunica media, the media‐to‐lumen ratio and connective tissue content were significantly increased in comparison with reference normotensive Wistar‐Kyoto (WKY) rats.3. Treatment for 8 weeks with a daily dose of 3 mg/kg of nicardipine decreased blood pressure values in SHR and significantly reduced the area occupied by the tunica media and the media‐to‐lumen ratio. This effect was observed primarily in small sized pial arteries and to a lesser extent in medium sized pial arteries. Nicardipine administration was without effect on connective tissue content in the wall of cerebral arteries.4. These results indicate that treatment with nicardipine reduces blood pressure elevation in SHR and exerts a protective effect on arteries controlling cerebrovascular resistance. The activity of the compound primarily on small sized pial arteries may protect the brain from generalized vasodilation which could cause cerebral hypoperfusion.
EFFECT OF BARNIDIPINE ON BLOOD FLOW TO MAJOR ORGANS AND RENAL FUNCTION IN ANAESTHETIZED DOGS AND SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Saitoh Minori , Kasai Chieko , Ishikawa Jun , Masaki Katsuhiro , Asano Masaharu 
Published: June 2007

Summary1. The effects of barnidipine on blood flow to major organs and on renal function were investigated in anaesthetized dogs and conscious spontaneously hypertensive rats (SHR), and the results were compared with those for nicardipine, nitrendipine, nisoldipine, manidipine and amlodipine.2. In anaesthetized dogs, barnidipine (0.3–3 μg/kg i.v.) dose‐dependently decreased blood pressure and increased or preserved blood flow in the vertebral, coronary, femoral and renal arteries. The effect of barnidipine on blood flow was the most potent of the compounds tested. In conscious SHR, barnidipine (0.3–3 mg/kg p.o.) produced a dose‐dependent antihypertensive effect and decreased renal vascular resistance. Barnidipine also dose‐dependently increased urinary volume. The antihypertensive and diuretic effects of barnidipine were the most potent of the drugs tested.3. In summary, barnidipine was shown to preserve or increase blood flow to major organs and to produce diuretic activity with a decrease in blood pressure. These findings suggest that barnidipine maintains or promotes renal function at antihypertensive doses.
EFFECT OF ANGIOTENSIN‐CONVERTING ENZYME INHIBITORS ON FRUCTOSE INDUCED HYPERTENSION AND HYPERINSULINAEMIA IN RATS
Authors: Erlich Y. , Rosenthal T. 
Published: June 2007

Summary1. The effect of angiotensin‐converting enzyme inhibitors (ACEI) enalapril, lisinopril and ramipril was studied on fructose‐induced hypertensive and hyperinsulinaemic rats.2. 60 Sprague‐Dawley rats were fed a fructose‐enriched diet for 5 weeks, which produced hyperinsulinaemia, hypertri‐glyceridaemia and hypertension. Beginning with week 3 of the diet, lisinopril (10 and 20 mg per kg per day), ramipril (5 and 10 mg/kg per day) and enalapril (20 mg/kg per day) were given daily in drinking water for 2 weeks to 10 rats in each drug group. Ten rats fed only the fructose‐enriched diet served as control.3. Systolic blood pressure was measured weekly by the indirect tail‐cuff method. Plasma insulin level was determined using RIA.4. Data indicate that ACEI improve insulin resistance induced by high‐fructose intake in rats; that despite their equal hypotensive effect, ACEI differ in their ability to improve insulin resistance; and that improvement of insulin resistance by ACEI is dose‐dependent.
SUPPRESSION OF VASCULAR TRANSFORMING GROWTH FACTOR‐β1 AND EXTRACELLULAR MATRIX GENE EXPRESSIONS BY CILAZAPRIL AND NIFEDIPINE IN HYPERTENSIVE RATS
Authors: Kim Shokei , Ohta Kensuke , Hamaguchi Akinori , Miura Katsuyuki , Yukimura Tokihito , Iwao Hiroshi 
Published: June 2007

Summary1. We investigated the protective effects of an angiotensin‐converting enzyme inhibitor (ACEI) and a Ca antagonist on vascular injury in hypertension.2. Thirteen week old stroke‐prone spontaneously hypertensive rats (SHRSP) were orally given cilazapril (ACEI 10 mg per kg day) or nifedipine (Ca antagonist 30 mg kg per day) for 12 weeks. After the treatment, the aorta and superior mesenteric artery were excised, and subjected to the extraction of RNA. mRNA levels for the transforming growth factor‐β1 (TGF‐β1) and extracellular matrix components such as fibronectin (FN), collagen type I (CoI), type III (CoIII) and type IV (CoIV) and laminin, were measured by northern blot analysis, using each specific cDNA probe.3. In the mesenteric artery of SHRSP, TGF‐β1 mRNA levels were increased compared with Wistar‐Kyoto (WKY) rats, being accompanied by a significant increase in mRNA levels for FN, CoI, CoIII, CoIV and laminin. In the aorta, only TGF‐bland fibronectin mRNAs were increased in SHRSP, but collagen and laminin were not increased.4. Both cilazapril and nifedipine, to similar extents, suppressed the above mentioned increased gene expressions in both mesenteric artery and aorta, being associated with the improvement of vascular hypertrophy.5. These results suggest that TGF‐Blmay be responsible for smooth muscle cell hypertrophy and the increased deposition of extracellular matrix in hypertensive blood vessels. Both cilazapril and nifedipine may lessen hypertensive vascular thickening, by suppressing the gene expression of TGF‐Bland extracellular matrix.
DO KININS MEDIATE CARDIOPROTECTIVE AND RENOPROTECTIVE EFFECTS OF CILAZAPRIL IN SPONTANEOUSLY HYPERTENSIVE RATS WITH RENAL ABLATION?
Authors: Kohzuki Masahiro , Yasujima Minoru , Kanazawa Masayuki , Yoshida Kazunori , Sato Tokutato , Abe Keishi 
Published: June 2007

Summary1. We assessed the potential of the kallikrein–‐kinin system in mediating the cardioprotective and renoprotective effects of an angiotensin‐converting enzyme inhibitor (ACEI), cilazapril (CIL) in rats with renal ablation.2. Eight week old spontaneously hypertensive rats (SHR) were subjected to 5/6 nephrectomy. One week after the operation, the rats were divided into 5 groups: (i) vehicle; (ii) CIL 1 mg/kg per day per os (p.o.); (iii) Hoe140 (HOE) 70 μg/kg per day given intraperitoneally (i.p.); (iv) CIL 1 mg/kg per day p.0. plus HOE 7 7μg/kg per day i.p.; (v) CIL 1 mg/kg per day p.o. plus HOE 70 μg/kg per day i.p. The treatment lasted for 4 weeks.3. CIL alone significantly reduced systolic blood pressure, urinary protein excretion, heart weight and serum creatinine level. HOE alone did not induce any significant changes in these parameters. CIL in combination with HOE (7 or 70 μg/kg per day) did not induce any changes in these parameters, in addition to those associated with the effects of CIL alone.4. These results indicate that the kallikrein‐kinin system might not play a major role in the cardioprotective and renoprotective effects of ACE inhibitors in the rat remnant kidney model of chronic renal failure.
PROTECTIVE EFFECT OF THROMBOXANE SYNTHETASE INHIBITOR ON HYPERTENSIVE RENAL DAMAGE IN DAHL SALT‐SENSITIVE RATS
Authors: Gomi T. , Ikeda T. , Sasaki Y. , Kosugi T. , Shibuya Y. , Sakurai J. 
Published: June 2007

Summary1. The effects of OKY‐046, a specific thromboxane (TX) synthetase inhibitor, on blood pressure, urinary excretion of TX and its release from blood platelets and renal papilla, and pathological change of glomeruli were evaluated in Dahl salt‐sensitive rats.2. Average daily intakes of OKY‐046‐treated rats were 0.93 mg/kg (low dose), 9.8mg/kg (moderate dose), and 88 mg/kg (high dose).3. Systolic blood pressure tended to decrease by 6.3, 11.4, and 10.9% in three OKY‐treated groups.4. OKY‐046 suppressed the release of TX from platelets in a dose‐dependent fashion. Both TX in urine and released from renal papilla decreased in OKY‐treated groups with moderate and high dose. OKY‐046 resulted no change in urinary excretion or release from renal papilla of prostaglandin E2 or 6‐keto‐prostaglandin F1α.5. Glomerular sclerosis score decreased significantly in both groups treated with moderate and high doses of OKY‐046.6. An inhibition of renal TX synthesis by TX synthetase inhibitor has a protective effect on the development of hypertensive renal damage with minor antihypertensive effect in Dahl salt‐sensitive rats.
ELECTROENCEPHALOGRAPHIC EVALUATION OF THE THERAPEUTIC EFFICIENCY OF ANTIHYPERTENSIVE AGENTS ON M‐SHRSP
Authors: Ohta Yoshio , Chikugo Taka‐aki , Suzuki Tsuneyuki , Chichibu Shiko 
Published: June 2007

Summary1. In order to evaluate the therapeutic effects of antihypertensive agents on malignant hypertension in M‐SHRSP, EEG were performed as a non‐invasive, therapeutic index.2. Under pentobarbital anaesthesia, the EEG pattern of rats with severe hypertension and/or cerebrovascular lesions showed alternate short‐active and long‐depressive phases with spike and sharp waves.3. When M‐SHRSP were treated with an angiotensin converting enzyme inhibitor (SQ 29,852) or a calcium antagonist (manidipine), the depressive phases became shorter and active phases longer. These changes were more prominent in manidipine treated rats than in SQ 29,852 treated rats.4. The EEG spike‐ and sharp‐wave complex seems to be a convenient index for evaluating cerebrovascular lesions and cerebral activity in M‐SHRSP.
IS THE M1‐MUSCARINIC RECEPTOR A CANDIDATE GENE FOR HYPERTENSION IN THE SPONTANEOUSLY HYPERTENSIVE RAT?
Authors: Klett Christoph P. R. , Printz Morton P. 
Published: June 2007

Summary1. Central nervous system muscarinic receptors have been implicated in genetic models of hypertension as well as in stress adaptive cardiovascular responses. To determine if the sequence of the M1‐muscarinic receptor is pathogenetic for hypertension, we analysed the differences between SHRLJ (spontaneously hypertensive rats) and WKYLJ (Wistar‐Kyoto) rats in the sequence of the M1‐receptor gene.2. Specific primer sets were synthesized so as to cover the gene in 10 fragments (158–344 base pairs) with overlaps. Analysis was conducted by both polymerase chain reaction (PCR)‐acrylamide and by single‐stranded conformation polymorphism (SSCP).3. No polymorphic locus was found by non‐denaturing PCR‐acrylamide nor by denaturing SSCP. Slight intrastrain variations in fragment 2 of the parental strains were examined by direct sequencing; however, no difference in sequence was found between SHRLJ and WKYLJ. TO identify the chromosomal location and possible linkage with a polymorphic locus, rat/mouse somatic hybrid cell lines were examined. The rat M1‐muscarinic receptor was assigned to chromosome 1.4. Based on analysis of the coding sequence of the gene, our data do not support the hypothesis that the M1‐muscarinic receptor is a candidate gene for hypertension. We conclude that, pending analyses of the promoter and regulatory regions of the gene, differences in the M1‐muscarinic receptor in SHR either in receptor expression or in physiological response must be due to altered intracellular signalling or extracellular transynaptic events, but not due to a mutation of the gene sequence.
ELEVATED SPONTANEOUS ACTIVITY OF PHENYLEPHRINE‐EXCITED NEURONS IN THE CAUDAL VENTROLATERAL MEDULLA OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Wong T. M. , Yang Z. , Chan Y. S. 
Published: June 2007

Summary1. The caudal ventrolateral medulla (CVLM) of pentobarbital‐anaesthetized spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) rats was identified by the depressor response with microinjection of glutamate.2. The mean firing rate of the spontaneously active phenyl‐ephrine‐excited CVLM neurons was significantly greater in SHR than in WKY. The pattern of neuronal firing in terms of coefficient of variation and skewness of the interspike interval histogram was similar in both types of rats.3. Administration to CVLM of kainic acid, an excitotoxic agent, led to a biphasic blood pressure response—a transient reduction followed by a gradual and sustained elevation. The elevation in blood pressure was significantly greater in SHR than in WKY.4. These findings suggest that the barosensitive CVLM neurons are more active and the tonic inhibitory influence from CVLM to rostral ventrolateral medulla (RVLM) is greater in SHR than in WKY. It is therefore not likely that the elevated spontaneous activity of the RVLM cardiovascular neurons in SHR is due to a smaller inhibitory influence from CVLM.
HYPOTHALAMIC AND MEDULLARY GABAA AND GABAb‐ERGIC SYSTEMS DIFFERENTLY REGULATE SYMPATHETIC AND CARDIOVASCULAR SYSTEMS
Authors: Takenaka K. , Sasaki S. , Nakamura K. , Uchida A. , Fujita H. , Itoh H. , Nakata T. , Takeda K. , Nakagawa M. 
Published: June 2007

Summary1. To determine whether hypothalamic and medullary GABA (gamma‐aminobutyric acid)B stimulation would affect the sympathetic and cardiovascular activities, and to determine whether these effects would be altered in hypertension, baclofen (a GABAb agonist) was injected into a hypothalamic pressor area (ventromedial hypothalamus, VMH), a depressor area (anterior hypothalamus, AH), or a nucleus tractus solitarius (NTS) in normotensive and spontaneously hypertensive rats (SHR).2. Intracetebroventricular (ICV) injections of a GABAa agonist (muscimol, 1 μg) decreased blood pressure (BP) and heart rate (HR). ICV injections of baclofen (2μg) elicited biphasic depressor and pressor effects, and these effects were abolished by a pretreatment with saclofen (GABAb antagonist, 100 μg, icv).3. Muscimol (400 ng) and baclofen (800 ng) injected into VMH decreased sympathetic nerve activity (SNA), BP and HR to almost similar levels, while saclofen injected into VMH increased HR without affecting BP levels.4. The same dose of baclofen injected into AH increased BP, but muscimol (AH) did not alter BP.5. Both muscimol and baclofen injected into NTS increased BP, but its magnitude was larger in baclofen injections.6. Depressor and sympathoinhibitory effects of baclofen (VMH) in SHR were larger than those in normotensive Wistar‐Kyoto (WKY) rats, while pressor responses elicited by baclofen (AH) did not differ between SHR and WKY.7. In summary, GABA reduces SNA, BP and HR through both GABAa and GABAb receptors in VMH. In addition, the GABAb system acts on AH and NTS to further regulate the cardiovascular activities. In SHR, GABAB‐ergic dysfunction in VMH but not in AH might contribute to the development of hypertension.
FUNCTIONAL ALTERATION OF THE GABAB RECEPTOR IN THE BRAIN OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Ichida Tatsuya , Sasaki Susumu , Takeda Kazuo , Kuriyama Kinya , Nakagawa Masao 
Published: June 2007

Summary1. We studied the ontogenetic development of GABAB receptors and their coupling to cyclic AMP formation in spontaneously hypertensive (SHR) and normotensive Wistar‐Kyoto (WKY) rat brains. GABAB receptor binding to various brain regions was compared in age‐matched SHR and WKY rats.2. The specific [3H]‐GABA binding to the posterior hypothalamus (PH) was significantly lower in not only 4 week old (normotensive) but also 11 week old (hypertensive) SHR, when compared with age‐matched WKY.3. Moreover, GABAB receptor agonists (baclofen and DN‐2327)‐induced suppression of adenylate cyclase activity also showed a decrease in 4 week old and 11 week old SHR PH.4. We concluded that the number and the functional responsiveness of GABAB receptors in rat brains decrease in SHR, preceding blood pressure elevation. The activity of GABABergic mechanisms may be different in the brains of SHR and WKY rats.
BARORECEPTORS IN THE CAROTID SINUS CONTRIBUTE TO ARTERIAL BARORECEPTOR REFLEXES IN NORMOTENSIVE RATS
Authors: Ohta H. , Talman W. T. 
Published: June 2007

Summary1. Baroreceptor reflex influences on renal sympathetic nerve activity (RSNA) were estimated with non‐linear regression analysis (sigmoidal curve fitting) before and after transection of carotid sinus nerves (CSN) and aortic depressor nerves (ADN) in rats.2. Transection of ADN reduced the gain of the reflex to 42% of basal levels with increases in arterial pressure (MAP) and RSNA. Subsequent transection of CSN eliminated the remaining sigmoidal correlation between MAP and RSNA without further changes in resting MAP and RSNA.3. By comparison, the transection of CSN reduced the gain of the reflex to 53% of basal levels without affecting other variables. Additional transection of both ADN eliminated the remaining sigmoidal correlation between MAP and RSNA with further increases in resting MAP and RSNA.4. These results indicate that carotid sinus baroreceptors exist in rats. They contribute to baroreceptor‐mediated reflex changes in RSNA as do aortic baroreceptors, although the working range of MAP may increase with transection of the latter.
α‐ADDUCIN MAY CONTROL BLOOD PRESSURE BOTH IN RATS AND HUMANS
Authors: Bianchi Giuseppe , Tripodi Maria G. , Casari Giorgio , Torielli Lucia , Cusi Daniele , Barlassina Cristina , Stella Paola , Zagato Laura , Barber Barry R. 
Published: June 2007

Summary1. Previous studies on the pathogenetic mechanisms of hypertension in the Milan hypertensive strain of rat (MHS) showed that a polymorphism within the α‐adducin gene is responsible for up to 50% of the blood pressure difference between MHS and their MNS normotensive control strain. A case‐control study has shown also in humans an association between α‐adducin locus and hypertension using 4 multiallelic markers surrounding the α‐adducin locus.2. With a multiple regression approach we provide an estimate of the contribution of the genotype for each marker to the blood pressure variability in comparison to that provided by sex, body mass index and age.3. While sex, body mass index and age contributed by about 40–45% to the overall blood pressure variability, the inclusion of the genotype for the marker closer to the α‐adducin locus provided a further increase of the variability explained of about 5%.4. The contribution independently provided by the other markers decreased exponentially with the increase of distance from α‐adducin locus.
ROLE OF CEREBRAL ATP‐SENSITIVE K+ CHANNELS IN ARTERIAL PRESSURE REGULATION DURING ACUTE CEREBRAL ISCHAEMIA IN SHR AND WKY RATS
Authors: Nishimura M. , Nanbu A. , Sakamoto M. , Nakanishi T. , Takahashi H. , Yoshimura M. 
Published: June 2007

Summary1. ATP‐sensitive K+ channels (KATP) are activated either by decreased intracellular ATP content or ATP/ADP ratio during ischaemia. We examined the role of a cerebral KATP in arterial pressure regulation during acute cerebral ischaemia using SHR and WKY rats. Thirteen week old male SHR or WKY rats were anaesthetized with urethane, and arterial pressure and heart rate were recorded under an artificial ventilation.2. Intracerebroventricular (i.c.v.) injections of glibenclamide, a specific inhibitor of KATP, elicited dose‐dependent vasopressor responses in WKY with bilateral ligation of carotid arteries, whereas it caused smaller vasopressor responses in SHR than WKY.3. Systemic administration of AVP V1 receptor antagonist, OPC‐21268, abolished the vasopressor responses of i.c.v. injections of glibenclamide in WKY but not in SHR.4. Intracerebroventricular injections of glibenclamide caused both the increase in plasma concentration of AVP and the decrease in pituitary AVP content in WKY with bilateral ligation of carotid arteries, whereas it elicited no significant change in plasma and pituitary concentration of AVP in SHR with bilateral ligation of carotid arteries.5. Cerebral KATP may play a role in the protection of excess hypertension by inhibiting AVP release from the pituitary glands during acute ischaemia in WKY, but this mechanism might not work in SHR during acute cerebral ischaemia.