bluuebunny/crossref_metadata_2025 huggingface dataset:
DISTINCT EXPRESSION OF TRANSFORMING GROWTH FACTOR‐β RECEPTOR SUBTYPES ON VASCULAR SMOOTH MUSCLE CELLS FROM SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR‐KYOTO RATS
Authors: Fukuda Noboru , Kubo Atsushi , Izumi Yoichi , Soma Masayoshi , Kanmatsuse Katsuo
Published: June 2007

1. We investigated the characteristics and expression of transforming growth factor‐β (TGFB) receptor subtypes on vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) rats.

2. TGF β binding assays revealed that VSMC from SHR showed higher number and affinity of TGF β receptors than cells from WKY rats.

3. The affinity labelling with [125I]‐TGFβ1 revealed the presence of TGFβ receptor subtypes with molecular sizes of 280, 85, 70 and 60kDa on VSMC from both strains at high cell density. The abundance of the 85 kDa receptor subtype was greater in VSMC from SHR than cells from WKY rats. The 85 kDa receptor subtype was not detected on VSMC from both strains at low cell density.

4. These results suggest distinct expression of TGFP receptor subtypes on VSMC from SHR and WKY rats, which may account for the exaggerated proliferative response of VSMC from SHR to TGFβ.
CHANGES IN VARIOUS TISSUES IN THE ARTERIAL WALL OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Saito Noboru , Okada Teruhiko , Shirota Masatoshi , Yagyu Kenichi , Takatsuji Hiroyoshi , Nishiyama Shoji , Enzan Hideo
Published: June 2007

1. Using stroke‐prone spontaneously hypertensive rats (SHRSP), stroke‐resistant spontaneously hypertensive rats (SHRSR) and Wistar‐Kyoto rats (WKY), vascular complications and the longevity of rats were investigated.

2. SHRSP aged more than 9.5 months tended to suffer from severe vascular complications such as periarteritis nodosa (PN) of mesenteric artery, while SHRSR very rarely showed severe vascular complications and WKY did not show any complications, because of the different level of systolic blood pressure.

3. Among some tissues PN tended to occur early in the small arteries of the testes and then in mesenteric artery, when these tissues of SHRSP were investigated microscopically.

4. Concerning the influence of systolic blood pressure on arterial smooth muscle layer, the deviation force of this layer was larger in SHRSR compared to WKY (44.7 times in Y axis), which was calculated mathematically and physically using computer analysis.

5. The arterial wall area of PN was enlarged, resulting in the low ratio of lumen/wall. The ratio of arterial lumen/wall was lower in SHRSP when compared to the age‐matched WKY.

6. In search for myocardial ischaemia, ECG was recorded. There were positive correlations between PQ interval or SV1+ R V5 and age in the three strains of rats. ST depression more than 1 mm on ECG was most prevalent in old SHRSP, indicating probably the presence of myocardial ischaemia.
CHARACTERIZATION OF RETINAL VASCULAR ABNORMALITIES IN LEAN AND OBESE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Huang Suber S. , Khosrof Samer A. , Koletsky Richard J. , Benetz Beth Ann , Ernsberger Paul
Published: June 2007

1. The obese SHR (Koletsky rat; SHR‐k) is a unique animal model for the study of microvascular changes associated with genetic obesity, spontaneous hypertension, endogenous hyper‐lipidaemia, and hyperinsulinaernic, non‐insulin dependent diabetes mellitus (Type II).

2. Lean and obese SHR‐k exhibit retinal vascular changes which have not been previously characterized and are more severe than previously described in other animal models of experimental hypertension or non‐insulin dependent diabetes.

3. Progressive retinal capillary dropout, capillary cell changes, vascular tortuosity and dilatation are severe. Vessels form elevated varicose vascular tortuosities which leak fluo‐rescein dye and which are more frequent in the obese SHR‐k. This study suggests that lean and obese SHR may be unique models for the study of multivariate factors in the pathogenesis of ischaemic neovascular proliferation.
INFLUENCE OF HYPERTENSIVE VASCULAR CHANGES IN INTRATESTICULAR ARTERIES ON SPERMATOGENESIS IN SHRSP
Authors: Itoh Naoki , Akagashi Keigo , Kumamoto Yoshiaki , Suzuki Tsuneyuki , Ohta Yoshio
Published: June 2007

1. The process of the spermatogenetic damage induced by hypertensive vascular changes was studied with stroke‐prone spontaneously hypertensive rats (SHRSP).

2. In SHRSP, hypertensive changes in intratesticular arterioles developed from 19 weeks of age.

3. At 23 weeks of age, a severe reduction in the number of mature and immature spermatids was observed.

4. The transferrin concentration in testicular cytosol was decreased at 23 weeks of age, suggesting that Sertoli cell function in SHRSP had regressed.

5. In conclusion, it was suggested that the decline in Sertoli cell function as a result of hypertensive vascular changes is part of the mechanism whereby spermatogenic damage occurs in SHRSP.
BIOCHEMICAL CHARACTERIZATION OF THE FIBRES OF COLLAGEN AND ELASTIN IN THE AORTIC WALL OF SHRSP
Authors: Matsumura Sueo , Kawazoye Seiji , Tian Sheng‐Fang , Takashima Toshinobu , Sunaga Toshiaki , Toda Shuji , Fujitani Noboru , Higashino Hideaki , Suzuki Aritomo
Published: June 2007

1. Vessel wall fragments consisting of collagen, elastin and other insoluble proteins were prepared from the aortas of 6 month old WKY and SHRSP and dead, elderly humans.

2. Prolonged incubations of these fragments with pepsin below or at 30°C resulted in different amounts of insoluble materials containing similar or larger proportions of collagen and other insoluble proteins than the respective vessel fragments. The amounts of the pepsin‐insoluble materials obtained from SHRSP were larger than those from WKY but were much smaller than those from elderly humans.

3. The elastins isolated from the vessel fragments were solubilized by pepsin much more effectively than the respective vessel fragments.

4. The pepsin‐insoluble materials from WKY were composed of thin mesh‐shaped materials, while those from SHRSP were composed of denser sheet‐shaped materials. While these materials from both rats did not contain a significant number of distinctive fibrils of collagen, the materials from elderly humans did contain numerous distinctive fibrils of collagen.

5. Large fractions of both the collagen and other proteins in the pepsin‐insoluble materials were solubilized by incubation with a crude bacterial collagenase below 30°C or by incubation with pepsin above 40°C where the triple‐helical regions of the collagens were unfolded.

6. These results appear to indicate that the aortic wall of SHRSP contains larger amounts of some insoluble components that immobilize the collagen fibrils than that of WKY, but the aortic walls of elderly humans contain much larger amounts of these components than that of SHRSP.
BLOOD PRESSURE‐RELATED CHANGES OF ENDOTHELIUM‐DEPENDENT RELAXATION IN THE AORTA FROM SHRSP AT DEVELOPMENTAL AGES OF HYPERTENSION
Authors: Tomita T. , Onda T. , Mashiko S. , Hamano M. , Tomita I.
Published: June 2007

1. Shear stress and flow influence endothelial functions to stimulate the release of endothelium‐derived relaxing factor (EDRF). However, it is not well defined how hypertension affects endothelial functions. In this study, blood pressure‐related changes of endothelium‐dependent relaxation (EDR) in the aorta were examined in SHRSP, WKY and FI hybrid at developmental ages of hypertension, and hypotensively‐treated SHRSP.

2. Acetylcholine‐induced EDR of aortic rings was significantly enhanced in 8 week old SHRSP compared with that of age‐matched WKY.

3. NG‐monomethyl L‐arginine (L‐NMMA) (1 mmol/L), an inhibitor of nitric oxide, greatly reduced the relaxation in both strains. Indomethacin (10‐5 mol/L), a cyclo‐oxygenase inhibitor, did not affect the relaxation at this age.

4. EDR was positively correlated (r = 0.81, n= 22) with blood pressure at 9 weeks of age in WKY, SHRSP and F1 hybrid.

5. A five week hypotensive treatment of SHRSP caused a significant reduction in EDR with decreasing blood pressure.

6. It was concluded that the endothelium releases more EDRF in response to increasing blood pressure to regulate vascular tone at developmental ages of hypertension.
COMPARATIVE STUDY ON FREE RADICAL INJURY IN THE ENDOTHELIUM OF SHR AND WKY AORTA
Authors: Ito H. , Torii M. , Suzuki T.
Published: June 2007

1. Using 13 week old SHR and WKY rats, aortic endothelial injury was examined after tert‐butylhydroperoxide (t‐BOOH) perfusion.

2. ESR analysis revealed a hydroxyl radical adducts in the perfusate after t‐BOOH perfusion.

3. After t‐BOOH perfusion, endothelial changes such as cauliflower‐like blebs and crater‐like holes were frequently observed in the SHR aorta, but rarely seen in the WKY aorta.

4. X‐ray spectra revealed the cerium perhydroxide deposition on the surface of endothelial cells of the SHR aorta.

5. These findings indicate that free radical injury is much more intense in the endothelial cells of SHR than in those in WKY.
INFLAMMATORY CYTOKINES AND RAT VASCULAR TONE
Authors: Ohkawa Fujio , Ikeda Uichi , Kanbe Toshiko , Kawasaki Kenichi , Shimada Kazuyuki
Published: June 2007

1. Experiments were performed to examine the effect of inflammatory cytokines, interleukin‐2 (IL‐2), IL‐6 and IL‐8, on the contractility of rat aorta.

2. Pretreatment of the endothelium‐denuded aortic ring with IL‐6 for 3h caused a significant inhibition of its contraction (58.9 ± 7.8%, n= 9, P < 0.01) when induced by 10−6mol/L phenylephrine.

3. On the other hand, IL‐2 and IL‐8 failed to show significant effects on the contractility of the aorta.

4. This inhibitory effect of IL‐6 on phenylephrine‐induced contraction showed dose‐dependency, and completely disappeared in the presence of 10−5mol/L indomethacin.

5. In cultured rat vascular smooth muscle cells (VSMC), the release of 6‐keto‐prostaglandin F1α into the extracellular medium was significantly increased by exposure to IL‐6, but not by exposure to IL‐2 or IL‐8.

6. IL‐2, IL‐6 and IL‐8 showed no effects on the release of nitrite, a stable metabolite of nitric oxide (NO), from VSMC.

7. These results indicate that IL‐6, not IL‐2 or IL‐8, is a potent inhibitor of the α‐adrenergic‐stimulated contraction of vascular smooth muscle and its action is mediated by the increased synthesis of prostacyclin rather than NO.
MAPPING OF ANGIOTENSIN II RECEPTOR SUBTYPES IN PERIPHERAL TISSUES OF SPONTANEOUSLY HYPERTENSIVE RATS BY IN VITRO AUTORADIOGRAPHY
Authors: Song Keifu , Kurobe Yoshiko , Kanehara Hironori , Wada Takeo , Inada Yoshiyuki , Nishikawa Kohei , Miyazaki Mizuo
Published: June 2007

1. The regulation of angiotensin II (AII) receptor subtypes was studied in peripheral tissues of 20 week old male spontaneously hypertensive rats (SHR) and age‐matched normotensive Wistar‐Kyoto (WKY) rats.

2. AII receptor binding was determined by a quantitative in vitro autoradiography using [125I]‐[Sar1, Ile8]AII as a ligand on the kidney, adrenal gland, thoracic aorta and heart. CV‐11974, a specific AT1 receptor antagonist, and CGP42112B, a specific AT2 antagonist, were used in competition with [125I]‐[Sar1, Ile8]AII to differentiate AT1 and AT2 receptor binding.

3. The relative abundance of each subtype was very similar between SHR and WKY rats. In both strains of rats, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors over glomeruli, proximal tubules and outer medulla. AT1 receptors were predominant in the thoracic aorta and heart.

4. As for relative receptor density, important differences were observed between SHR and WKY rats. In SHR, the adrenal cortex, outer medulla of the kidney, and heart displayed higher AT1 receptor density than WKY rats.

5. These results indicate that the expression of AT1 receptors is differently regulated in some important targets of AII in SHR, and suggest that the altered regulation of AT1 receptor presented in this study should be relevant to the patho‐physiological features of SHR.
ELEVATED GLUCOSE CONCENTRATION AND NATRIURETIC PEPTIDES RECEPTOR RESPONSE ON VASCULAR SMOOTH MUSCLE OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Yasunari Kenichi , Kohno Masakazu , Kano Hiroaki , Hanehira Takao , Minami Mieko , Ikeda Miwako , Horio Takeshi , Yokokawa Koji , Takeda Tadanao
Published: June 2007

1. Hyperglycaemia is believed to be a major cause of diabetic vascular complications such as accelerated atherosclerosis. In order to elucidate the effect of hyperglycaemia on vascular response in spontaneously hypertensive rats (SHR), the natriuretic peptides receptor responses to vascular smooth muscle cells (VSMC) which are thought to suppress atherosclerosis were studied under high glucose (HG:22.2 mmol/L) conditions.

2. The total number of cells in SHR is higher and natriuretic peptides receptor response is smaller than that of cells in the Wistar‐Kyoto (WKY) rat. Membrane bound protein kinase C (PKC) activity in HG or SHR is higher compared to that of cells in normal glucose (NG:5.6 mmol/L) or WKY. Cells cultured in HG for at least 2 passages had higher total cell number and receptor mediated cGMP formation were suppressed compared to cells cultured in NG both in SHR and WKY. Specific PKC inhibitor PKC (19–36) 1 μmol/L prevented HG induced suppression of natriuretic peptides response.

3. These results show that hyperglycaemia may be linked to suppressed natriuretic peptides receptor response which is caused by increased PKC activity both in WKY and SHR. This suppressed response may cause the accelerated atherosclerosis by hyperglycaemia.
GENE REGULATION OF BRAIN NATRIURETIC PEPTIDE IN CARDIOCYTE HYPERTROPHY BY α1‐ADRENERGIC STIMULATION
Authors: Nakagawa O. , Itoh H. , Harada M. , Komatsu Y. , Yoshimasa T. , Nakao K.
Published: June 2007

1. We previously demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone mainly produced in the ventricle, while the major production site of atrial natriuretic peptide (ANP) is the atrium. The production and secretion of BNP and ANP in the hypertrophied ventricles were markedly augmented, serving as a compensation mechanism against ventricular overload by their natriuretic, diuretic and vasodilatory actions.

2. In the present study, we prepared an in vitro model of cardiocyte hypertrophy using cultured neonatal rat ventricular cardiocytes and αl‐adrenergic stimulation, and examined the gene expressions of BNP and ANP during the process of cardiocyte hypertrophy.

3. The treatment of cultured ventricular cardiocytes with phenylephrine evoked cardiocyte hypertrophy around 24 h after the treatment, which was characterized by augmented expression of the myosin light chain‐2 gene and increase in cell size.

4. In this model of cardiocyte hypertrophy, the steady‐state level of BNP mRNA rapidly increased to the maximal level within 1 h after the treatment. In contrast, ANP mRNA began to increase at 3h, and accumulated during the course of cardiocyte hypertrophy. The secretion of BNP from ventricular cardiocytes was also stimulated more rapidly than the ANP secretion.

5. These results indicate that the gene expression of BNP is distinctly regulated from that of ANP in cardiocyte hypertrophy, and suggest a discrete pathophysiological role of BNP as an ‘emergency’ cardiac hormone against ventricular overload.
AUGMENTED EXPRESSION OF THE ENDOTHELIN‐A RECEPTOR GENE IN CULTURED MESANGIAL CELLS FROM STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Hiraoka Junko , Arai Hiroshi , Yoshimasa Takaaki , Takaya Kazuhiko , Miyamoto Yoshihiro , Yamashita Jun , Suga Shin‐ichi , Ogawa Yoshihiro , Shirakami Gotaro , Itoh Hiroshi , Yamori Yukio , Nakao Kazuwa
Published: June 2007

1. To elucidate the role of endothelin (ET) receptor in hypertension, we studied the expression of the ET‐A receptor (ET‐ AR) gene and the ET‐B receptor (ET‐BR) gene in cultured mesangial cells isolated from stroke‐prone spontaneously hypertensive rats (SHRSP) and Wistar‐Kyoto (WKY) rats.

2. The mesangial cells from both SHRSP and WKY expressed ET‐AR predominantly. The level of the ET‐AR mRNA in mesangial cells from SHRSP was 5‐fold higher than that in the cells from WKY. The ET‐BR mRNA in the mesangial cells from both strains was hardly detectable by northern blot analysis.

3. These results demonstrate that the expression of the ET‐AR gene was markedly augmented in mesangial cells from SHRSP.
ENHANCED PHOSPHOINOSITIDE TURNOVER SIGNALLING STIMULATED BY ENDOTHELIN B‐TYPE RECEPTOR IN ENDOTHELIAL CELLS FROM SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Yokokawa K. , Kohno M. , Minami M. , Ikeda M. , Horio T. , Kano H. , Hanehira T. , Yasunari K. , Takeda T.
Published: June 2007

1. Endothelin (ET) B‐type (ETB) receptor‐mediated signal transduction was examined after stimulation with ET‐3 in cultured aortic endothelial cells (EC) from spontaneously hypertensive (SHR) and Wistar‐Kyoto (WKY) rats (8 weeks old).

2. The EC from both rat strains expressed only ETB receptor mRNA. The receptor densities and affinities, which were non‐selective for ET‐1, ‐2, ‐3 and Sarafotoxin S6c, and mRNA expression were similar in WKY and SHR.

3. The cytosolic Ca2+ level in the absence of extracellular Ca2+, inositol 1,4,5‐trisphosphate levels, protein kinase C and phospholipase C activities in response to ET‐3 were greater in SHR EC than in WKY EC.

4. The 45Ca uptake in response to ET‐3, which was blocked by Ni2+, was smaller in SHR EC than in WKY EC.

5. The 6‐keto‐PGF1α production was augmented in SHR, though nitric oxide formation after stimulation with ET‐3 was similar.

6. These results suggest that ETB receptor‐mediated phosphoinositide turnover signalling is augmented in SHR EC through postreceptor mechanism.
EFFECT OF THROMBIN AND PDGF ON ENDOTHELIN PRODUCTION IN CULTURED MESANGIAL CELLS DERIVED FROM SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Ikeda Miwako , Kohno Masakazu , Horio Takeshi , Yasunari Kenichi , Yokokawa Koji , Kano Hiroaki , Minami Mieko , Hanehira Takao , Fukui Toshiki , Takeda Tadanao
Published: June 2007

1. Basal endothelin‐1 (ET‐1) production in mesangial cells of spontaneously hypertensive rats (SHR) was not different from that of Wistar‐Kyoto (WKY) rats, although a trend toward increased ET‐1 production was observed in these cells of SHR.

2. Thrombin and platelet‐derived growth factor (PDGF) stimulated ET‐1 production in a concentration‐dependent manner in these cells of both rat strains, but thrombin‐ and PDGF‐induced stimulation of ET‐1 production were clearly greater in cells of SHR than WKY rats.

3. The protein kinase C (PKC)‐activating phorbol ester, phorbol myristate acetate, stimulated ET‐1 production in cells of both rat strains, but this stimulation was significantly greater in cells of SHR than in cells of WKY rats.

4. An inactive enantiomer of phorbol ester, 4a‐PDD, had no effect on the ET‐1 production in these cells of both rat strains.

5. Neither thrombin nor PDGF stimulated ET‐1 production in PKC‐depleted cells of both rat strains.
COMPARATIVE HAEMODYNAMIC STUDIES OF ENDOTHELIN‐1, ‐2 AND ‐3 ON CONSCIOUS SHRSP AND WKY
Authors: Higashino H. , Simeonova K. , Lambev I. , Suzuki A.
Published: June 2007

1. Depressor and pressor effects of endothelin‐1, ‐2 and ‐3 in relation to hypertension were investigated in conscious WKY and SHRSP.

2. Changes of systolic arterial pressure to both depressor and pressor responses caused by three doses of endothelin‐1, ‐2 or ‐3 (0.1, 0.3 and 1 nmol/kg) occurred to a similar extent between WKY and SHRSP. These data showed that endothelins may not exert an important role on the pathogenesis of hypertension.

3. Endothelin‐1 decreased the cardiac index more in SHRSP than in WKY, indicating the dominance of ETA receptors in SHRSP compared with WKY.

4. ET‐1 was the most potent vasodepressor and vasodilator of three endothelin peptides in rats.

5. During the pressor responses to endothelin‐1 and ‐3, cardiac arrhythmia was observed with high frequency in the animals of both groups, indicating the arrhythmogenic effect of ET.
A NEW LOCUS ON CHROMOSOME 3 STRONGLY LINKED WITH SALT‐SENSITIVE HIGH BLOOD PRESSURE IN FEMALE F2 FROM SHRSP AND WKY RATS
Authors: Matsumoto Ciho , Nara Yasuo , Ikeda Katsumi , Nabika Toru , Sawamura Makoto , Yamori Yukio
Published: June 2007

1. We investigated candidate loci for salt‐sensitive high blood pressure in F2 progeny from crossing Wistar‐Kyoto rats and stroke‐prone spontaneously hypertensive rats.

2. The average systolic and diastolic blood pressure did not increase in male and female F2 progeny by the 12th day after salt loading.

3. In female F2 progeny, systolic and diastolic blood pressure became strongly linked with the MITR244 locus on chromosome 3,1 month and 12 days after salt loading.

4. This locus became linked with blood pressure only in the female F2 progeny and not in the males.

5. These results indicate that hormonal factors and gender differences, in particular, might influence salt sensitivity.
EFFECTS OF A HIGH‐SALT DIET ON TISSUE NORADRENALINE CONCENTRATIONS IN DAHL SALT‐RESISTANT AND ‐SENSITIVE RATS
Authors: Chen Q. H. , Morita H. , Nishida Y. , Hosomi H.
Published: June 2007

1. We measured systolic arterial pressure (SAP) and tissue noradrenaline concentrations (tNA) of 16 organs (heart, kidney, aorta, brain stem, pancreas, spleen, stomach, jejunum, ileum, colon, lung, muscle, cerebrum, liver, bone, salivary gland) in Dahl salt‐resistant (DSR) and ‐sensitive rats (DSS) fed 0.4 (0.4%) or 8% salt diet (8%) from 5 weeks old until the age of 5, 7, 9 and 11 weeks.

2. SAP increased in DSS with the 8% salt diet. An increased rate of SAP of DSS with the 0.4% salt diet was larger than DSR with the 0.4% diet. In DSR with 0.4%, tNA tended to increase from 5 weeks old except in the bone, which may have been the result of ageing. In DSS with 0.4%, tNA did not increase from 5 weeks old. DSS showed salt‐sensitivity even to 0.4%.

3. tNA of the heart and kidney of both DSS and DSR with 8% were lower than 0.4%. These organs are high‐salt‐sensitive organs. tNA of the aorta, spleen, stomach, jejunum, ileum, and colon of DSS with 8% were lower than 0.4%, but not DSR. These organs are medium salt‐sensitive organs. tNA of the pancreas of DSS with 8% was lower than 0.4% which was not different from DSR with 0.4 and 8%. The pancreas is a low salt‐sensitive organ. tNA of the lung, muscle, cerebrum, liver, bone and salivary gland did not show any differences between 0.4 and 8% in DSS as well as DSR. These organs are not salt‐sensitive organs.

4. There were large organ differences in tNA among organs studied. There were large organ differences in decrease rate of tNA in response to a high‐salt diet. The organ function and the period of salt diet influence tNA.
MAGNESIUM, CALCIUM AND TRACE ELEMENTS IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Saito Noboru , Abbu G. C. , Konishi Yuuko , Nishiyama Shoji , Okada Teruhiko
Published: June 2007

1. Using three strains, which showed severe hypertension, mild hypertension and normotension, respectively, the relationships between electrolytes or trace elements and vascular complications combined with the factor of ageing were investigated.

2. In ash materials of some tissues old female SHRSP and old WKY showed a decrease of selenium in many tissues when compared to adult female SHRSP and WKY, respectively.

3. In cellular supernatant fraction, SHRSP showed a decrease of magnesium in many tissues and an elevation of the calcium to magnesium ratio when compared to age‐matched WKY and SHRSR.

4. In diabetic rats induced by streptozotocin, myocardial magnesium decreased, resulting in an elevation of the myocardial calcium to magnesium ratio.

5. Alpha tocopherol concentration was lower in both the myocardium and cerebrum of old female SHRSR when compared to that of adult female SHRSR.

6. From these findings the elevation of calcium to magnesium ratio was found in old rats and SHRSP, indicating the tendency of tissue deterioration in these rats.

7. Tissue selenium also decreased in old rats and SHRSP and this decrement was probably related to the peroxidation in tissue damage.
PECULIARITIES OF THE CELLULAR ION‐TRANSPORT FUNCTION OF THE GASTROINTESTINAL TRACT IN HYPERTENSIVE RATS
Authors: Smirnov Y. , Oslopov V. , Sorokina N. , Maklakov A. , Stolpner E.
Published: June 2007

1. A study of gastric and intestinal mucosa samples of 15 SHR and 15 normotensive rats of the line WKY was performed by proton‐pulsed NMR with a pulsed magnetic field gradient.

2. The diffusion decay shape under the effect of the magnetic field gradient for intestinal mucosa cells in SHR and WKY appeared to be similar and differed drastically for gastric mucosa cells. The signal population of slow protons in SHR was lower and, with regard to fast protons, was higher than that in WKY.

3. The amount of slow protons is connected with low molecular cytoskeleton proteins. The decrease of their amount in hypertensive rats can be used as a test for cell membrane defects and explains, to some extent, the increase of membrane permeability for ions in the case of essential hypertension. This phenomenon is observed only in an acid medium (with increased proton concentration).
AUGMENTED Ca2+ MOBILIZATION IS A HYPERTENSIVE TRAIT DISCRIMINATED FROM A ‘MAJOR GENE’ IN BACKCROSS ANALYSIS BETWEEN SHR AND DONRYU RATS
Authors: Ohno Yoichi , Suzuki Hiromichi , Matsuo Koichi , Tanase Hisao , Takano Toshiya , Saruta Takao
Published: June 2007

1. Blood pressure and Ca2+ mobilization were significantly greater in SHR than in Donryu and F1 rats.

2. Backcross linkage analysis between spontaneously hypertensive rats and normotensive Donryu rats was performed to dissect polygenic hypertensive traits and to detect the existence of a single ‘major gene’.

3. Cluster and discriminant analysis of a scattergram of blood pressure versus Ca2+ mobilization classified the back‐crossed rats into two groups. The two groups were referred to the higher group and the lower group with regard to their relative blood pressure values.

4. Blood pressure was correlated with Ca2+ mobilization in each group; the correlation coefficients were 0.41 for the higher group (P < 0.01) and 0.71 for the lower group (P < 0.0001).
DIFFERENCES IN THE CHARACTERIZATION OF THE Ca2+ CURRENT IN VENTRICULAR MYOCYTES BETWEEN SPONTANEOUSLY HYPERTENSIVE RATS AND NORMOTENSIVE RATS
Authors: Nakata Tomoe , Sato Sadayuki , Hachisu Mitsugu , Tsutsumi Takeshi , Osada Hirofumi
Published: June 2007

1. The slow inward Ca2+ current elicited at the membrane potential ‐ 30 mV in SHR and normotensive Wistar rats (WR) with voltage‐clamp recording was examined for this study.

2. The maximal Ca2+ current of WR in the current‐voltage relationship showed the unified membrane potential of + 10 mV and the amplitude was −1.2 ± 0.2PA. In the case of SHR, however, the maximal Ca2+ current showed a lower and variable membrane potential between 0 and −20 mV. The amplitudes were −1.7 ± 0.9 pA at 0mV, −2.1 ± 0.8 pA at −10mV and −4.4 ± 0.3 pA at −20mV.

3. From the cell‐attached patch‐clamp recording, the conductance of unitary Ca2+ current and the slope value were the same in SHR and in WR. From the open‐time histogram of the Ca2+ channel, the open state probability in SHR increased and the time constant from the exponential curve became slightly extended in SHR.

4. L‐isoproterenol at 10‐6mol/L increased the Ca2+ current in SHR and WR. The increased ratio of Ca2+ current by I‐isoproterenol was smaller in SHR than that in WR.

5. The aspect of 1–4 suggests that the increase in Ca2+ current in SHR obtained by the voltage‐clamp was explained partly by the increase of open‐state probability of unitary Ca2+ channel activity, and that a possibility of Ca+2 channel being activated by phosphorylation through cAMP did not eventuate.
SPIN‐LABELLING STUDY OF BIOMEMBRANES IN SPONTANEOUSLY HYPERTENSIVE RATS: CALCIUM‐ AND CALMODULIN‐DEPENDENT REGULATION
Authors: Tsuda Kazushi , Minatogawa Yohsuke , Iwahashi Hideo , Nishio Ichiro , Kido Ryo , Masuyama Yoshiaki
Published: June 2007

1. The present study was performed to investigate alterations in membrane characteristics of spontaneously hypertensive rats (SHR) by using an electron paramagnetic resonance (EPR) and spin‐labelling methods.

2. Washed erythrocytes from SHR were examined and compared with erythrocytes from age‐matched normotensive Wistar‐Kyoto (WKY) rats.

3. The values of outer hyperfine splitting (2T'll) and that of the order parameter (S) obtained from EPR spectra for a spin label agent (5‐nitroxide stearate) were significantly higher in the erythrocytes of SHR than in those of WKY rats.

4. When calcium (Ca2+) was loaded to erythrocytes with a Ca2+ ionophore (A 23187), the order parameter (S) of the EPR spectra showed a greater increase in SHR than in WKY rats. Furthermore, the Ca2+‐induced change in the order parameter (S) of SHR was significantly antagonized by pretreatment of the Ca2+ antagonists (verapamil, diltiazem) and a calmodulin antagonist (W‐7).

5. The results show that the erythrocyte membranes of SHR tolerated different spin motions from those of normotensive WKY rats in the EPR study, which might be associated with the idea that the membrane fluidity might be lower in SHR. Furthermore, the data suggest that Ca2+‐calmodulin antagonists may ameliorate the Ca2+‐induced changes in membrane functions in hypertension.
REGULATION OF VASCULAR CONTRACTION BY IONIC MATRIX SURFACES OF THE SMOOTH MUSCLE CELL: CHANGES IN SHR?
Authors: Kravtsov G. M. , Kwan C. Y.
Published: June 2007

1. KCl‐induced contractions in aortic rings of spontaneously hypertensive rats (SHR) and two normotensive strains, Sprague‐Dawley (SD) and Wistar‐Kyoto (WKY) rats, were studied.

2. The contraction elicited by isotonic Na‐free, KCl solution containing 2.5mmol/L Ca and 1 mmol/L Mg was concentration‐dependently inhibited by Na and K. Maximal inhibition was induced by 20 mmol/L NaCl in WKY and SHR (65 and 85%, respectively) and by 60 rnmol/L NaCl in SD (50%). KCl (10–40 mmol/L) had no effect on SD but produced almost full relaxation in WKY and about 50% relaxation in SHR.

3. Isotonic Ca‐free, Na‐free high Mg (2 mmol/L), K‐solution caused strong phasic contractions in WKY and SHR, but weak responses in SD.

4. Aortic rings of SD, WKY and SHR developed strong, sustained and reproducible contractions in isotonic Ca‐free, Na‐free, K‐solution containing EDTA, which were fully relaxed by 1.2, 1.6 and 8 mmol/L Na, respectively.

5. We suggest that the primary mechanism of KCl‐contraction is potential‐independent competition between monovalent and divalent cations for binding sites on both surfaces of the plasma membrane (e.g. K with Mg and Na with Ca) and that differences in aortic contractility in SHR, WKY and SD merely reflect strain differences in the composition of the ionic matrix, independent of hypertension.
INTESTINAL CALCIUM ABSORPTION AND RESPONSE OF CALCIUM REGULATING HORMONES IN THE STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RAT AS A MODEL OF OSTEOPOROSIS
Authors: Fukuda Satoshi , Tsuchikura Satoru , Iida Haruzo , Ikeda Katsumi , Nara Yasuo , Yamori Yukio
Published: June 2007

1. Because of low levels of serum calcium (Ca) in stroke‐prone spontaneously hypertensive rats (SHRSP), intestinal Ca absorption and urinary Ca excretion were examined.

2. SHRSP were observed to have lower intestinal Ca absorption and higher urinary Ca excretion, but with a latent function of intestinal Ca absorption able to respond with calcium regulating hormones to Ca loading in the aged, especially to a new Ca agent as examined in this study.
COMPARISON OF THE EFFECTS OF HYPERCHOLESTEROLAEMIA ON RELAXATION RESPONSES IN AORTAS OF SPONTANEOUSLY HYPERTENSIVE RATS AND DAHL SALT‐SENSITIVE RATS
Authors: Kitagawa S. , Sameshima E. , Yamaguchi Y. , Kwon Y. , Shinozuka K. , Kunitomo M.
Published: June 2007

1. We investigated the effects of hypercholesterolaemia on relaxation responses in thoracic aortas isolated from two different types of hypertensive rats; spontaneously hypertensive rats (SHR) and Dahl salt‐sensitive rats (DSR).

2. All rats fed the high cholesterol diet for 8 weeks showed a significant increase in the serum cholesterol level. The high‐cholesterol diet did not change the blood pressure of SHR, but increased that of hypertensive DSR fed a high‐salt diet.

3. In aortas of SHR, the high‐cholesterol diet did not change the endothelium‐dependent and ‐independent relaxation induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively.

4. In aortas of hypertensive DSR, the high‐cholesterol diet notably reduced the ACh‐induced relaxations and slightly reduced SNP‐induced relaxation.

5. These results suggest that hypercholesterolaemia causes greater impairment of endothelium‐dependent relaxation in rat aorta with salt‐induced hypertension than genetic hypertension.
INCREASED IMMUNOREACTIVITIES FOR THE BASIC FIBROBLAST GROWTH FACTOR AND ITS RECEPTOR IN ASTROCYTES AT THE SITE OF CEREBRAL LESIONS AND OEDEMATOUS CHANGE IN SHR
Authors: Kataoka Hideo , Yamada Eiji , Hayase Yoneko , Hazama Fumitada
Published: June 2007

1. To obtain information about changes of basic fibroblast growth factor (bFGF) in the brain in chronic hypertension, we immunohistochemically studied the distribution and level of bFGF and its receptor in the brain of stroke‐prone spontaneously hypertensive rats (SHRSP).

2. In the control normotensive rats, immunoreactivity for bFGF was demonstrated in nerve cells, while there was almost no reactivity in astrocytes.

3. In SHRSP, there was a marked immunoreactivity in the densely accumulated reactive cells, particularly astrocytes, in and around cerebral cortical lesions. Slightly increased reaction for bFGF was found in the nerve cells around lesions. Astrocytes in the subcortical white matter on both ipsi‐ and contra‐lateral sides of the cortical lesion also showed immunoreactivity for bFGF. The location of increased bFGF expression in SHRSP corresponded very well with the site of extravasated plasma fluid demonstrated by anti‐fibrinogen antibody. Electron microscopically, bFGF was shown in astrocytes along the rough endoplasmic reticulum suggesting the growth factor to be produced in the cells and not to be taken up from the surroundings. Expression of FGF‐receptor was also demonstrated in reactive astrocytes in the oedematous cortical portion around lesion and in the oedematous subcortical white matter.

4. These findings indicate the possibility that oedema and the simultaneously generated free radicals or some extravasated plasma components express bFGF in astrocytes and probably in nerve cells as well as FGF‐receptor in astrocytes, and that the thus expressed bFGF and its receptor play some role in the sequence of developmental events of hypertensive cerebral lesions.
MITOCHONDRIAL ABNORMALITIES IN HYPERTROPHIED MYOCARDIUM OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Tokoro T. , Ito H. , Maenishi O. , Suzuki T.
Published: June 2007

1. To clarify the pathogenesis of cardiac disorders in SHRSP which showed severe cardiac hypertrophy and myocardial degeneration in the hypertensive stage, restriction fragment length polymorphisms (RFLP) of mitochondrial DNA (mtDNA), and morphological and functional changes of mitochondria were examined.

2. Morphologically, the mitochondrial size showed a wider range of distribution in SHRSP both at prehypertensive and hypertensive stage compared to those in age‐matched WKY.

3. Isocitrate dehydrogenase (ICDH) activity, but not super‐oxide dismutase (SOD) activity, was higher in the young SHRSP, whereas both enzyme activities were lower in the mature SHRSP than in the age‐matched WKY.

4. RFLP analysis by electrophoresis revealed that the loss of two restriction sites for Rsa I in the myocardial mtDNA from the SHRSP, but not in that from the WKY.

5. These findings suggest that the structural changes of mtDNA could be related, at least partly, to morphological and functional changes of mitochondria in the SHRSP myocardium.
CHRONIC EXOGENOUS HYPERINSULINAEMIA ACCELERATES THE DEVELOPMENT OF HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Bursztyn Michael , Ben‐Ishay Drori , Mekler Judith , Raz Itamar
Published: June 2007

1. An association between hyperinsulinaemia, insulin resistance and hypertension was previously described in spontaneously hypertensive rats (SHR). We therefore tested whether chronic exogenous hyperinsulinaemia, which did not affect blood pressure of normotensive rats, may aggravate hypertension in young SHR.

2. Insulin was administered for 4 weeks by a graded increase of a sustained release insulin implant, without carbohydrate supplementation.

3. Initial bodyweight of seven SHR and five sham‐implanted control SHR, aged 6–8 weeks, was not different between the groups or by week 4.

4. Glucose levels decreased in the treated rats [2‐way anova F (1:10) = 18.7. P < 0.005] and were 7.3 ± 0.1 mmol/L in the controls and 4.4 ± 0.7 mmol/L in the treated SHR, respectively. Insulin levels were comparable at baseline and increased to 1002 ± 978 pmol/L in treated rats at week 4 while remaining 270 ± 78pmol/L in the controls [F (1:10) = 6.1, P < 0.05]. The systolic blood pressure (tail‐cuff) was significantly increased in insulin treated SHR in weeks 1–3 [F (1: 10) = 5.1, P < 0.05] though it was comparable at baseline and week 4.

5. In the presence of a hypertensive predisposition, chronic exogenous hyperinsulinaemia accelerates the time course of the development of hypertension without affecting its severity.
ALTERED UTERINE ENVIRONMENT IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Erkadius E. , Morgan T. O. , Di Nicolantonio R.
Published: June 2007

1. In order to determine the role of the uterine environment in the development of hypertension in the spontaneously hypertensive rat (SHR) we examined the patterns of fetal and placental growth and the composition of amniotic fluid of SHR and normotensive Wistar‐Kyoto (WKY) rats during the final trimester of pregnancy.

2. SHR and WKY embryos and amniotic fluid were collected at days 15 and 20 of pregnancy, and fetal and placental weight and amniotic fluid volume were recorded. The sodium and potassium concentration of amniotic fluid was also measured.

3. Fetal and placental weights were significantly lower in SHR compared to WKY at 15 and 20 days of gestation. Amniotic fluid volume was significantly lower in SHR at 15 days, but significantly higher at 20 days. Amniotic fluid sodium concentration was significantly lower in SHR at 15 days but not different at 20 days when compared to WKY. Potassium concentration was lower in SHR at both ages.

4. Thus the reduced placental weight early in the gestational period of the SHR may play a role in its underdevelopment in utero and hence its reduced birthweight. The SHR foetus is also bathed in a hypokalaemic amniotic fluid of increased volume. How this might influence fetal development and later blood pressure is unclear. Also whether these changes are of maternal or fetal origin remain to be determined.
PLACENTAL NA+, K+ ACTIVATED ATP‐ASE ACTIVITY IN SHRSP IN CONNECTION WITH PREGNANCY INDUCED HYPERTENSION AND INTRA‐UTERINE GROWTH RETARDATION
Authors: Fuchi Isao , Higashino Hideaki , Noda Kiichiro , Suzuki Aritomo , Matsubara Yoshiharu
Published: June 2007

1. Placental Na+, K+‐ATPase activities were measured in connection with the active transport of amino acid, intrauterine growth retardation (IUGR) or small for date infants (SFD) in salt‐loaded pregnant SHRSP.

2. All parameters such as fetal weight, placental weight and Na+, K+‐ATPase activity in the placental tissue were significantly depressed in SHRSP, especially in the salt‐loaded SHRSP compared with WKY.

3. Besides a decrease of blood flow, a decline of Na+, K+‐ATPase activity associated with an active transport of amino acid in the placenta would cause IUGR and SFD in the salt‐loaded pregnant SHRSP.

4. Pregnant SHRSP given water containing salt would be a good model for pregnancy induced hypertension in humans.
STUDIES ON PREGNANCY HYPERTENSION AND IUGR‐SFD EFFECTS OF DRUGS ON THE BLOOD VESSELS IN THE PLACENTA OF PREGNANT SHRSP
Authors: Fuchi Isao , Noda Kiichiro , Matsubara Yoshiharu
Published: June 2007

1. Based upon our previous work, we came to the conclusion that a decrease in placental blood volume was a possible factor behind intrauterine growth retardation (IUGR) in pregnancy‐induced hypertension.

2. In a second study, we used an image analysis system to measure cross‐sectional areas and wall thicknesses of central blood vessels of the spiral artery, the so‐called ‘central artery’.

3. It was thought that one of the more basic factors behind IUGR in pregnancy‐induced hypertension might possibly be narrowings and spasms of the maternal placental blood vessels.

4. In this study, we found that the three drugs we used (MgSO4.7H2O, Solcoseryl and KCl) all resulted in an enlargement of the cross‐sectional areas of the maternal blood vessels, and that MgSO4.7H2O, in particular, also relaxed maternal blood vessel spasms in SHRSP placenta.
ELECTROMYOGRAPHY DATA ON SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Jacupow Eduard Z. , Khasanova Dina R. , Oslopow Vladimir N. , Khasanow Niyaz R. , Ismagilow Maxum F.
Published: June 2007

1. To investigate the state of nerve‐muscle excitability in 20 spontaneously hypertensive rats and 22 Wistar rats local electromyography was carried out in periods of rest and under the maximum strain of 10 min ischaemia of m.flexor femoris (Trusso's test).

2. The electromyography phenomenon found in the SHR group corresponds to typical tetany electromyography correlatives.

3. Thus, changes occur to the nerve‐muscle excitability state according to the neurogenic tetany type.
PROPER MEASUREMENT OF BLOOD PRESSURE AND HEART RATE IN SHRSP AND WKY BY AN INDIRECT VOLUME‐OSCILLOMETRIC METHOD
Authors: Higashino H. , Sirneonova K. , Lambev I. , Markov M. , Suzuki A.
Published: June 2007

1. The effect of environmental temperature on the indirect measurement of rat blood pressure and heart rate was investigated with special reference to the tail arterial blood flow in both strains of SHRSP and WKY.

2. Very good correlations (r > 0.82, P < 0.05; t‐test, 10 d.f.) were observed between the two values of systolic blood pressure or heart rate measured by a direct and an indirect method at environmental temperatures between 26 and 38°C in SHRSP, and 34 and 38°C in WKY, respectively.

3. When the temperature was elevated by 10°C from 25°C to 35°C, the regional blood flow in the tail artery increased by 52–69%, sufficient to detect a blood flow increase by the indirect method.

4. These data showed that the best way to measure the accurate blood pressure and heart rate in both strains of SHRSP and WKY by the indirect volume‐oscillometric method was to hold the rats at 34–36°C for 5 min.
EFFECTS OF NUTRITIONAL FACTORS ON REPRODUCTION, GROWTH, PREWEANING REFLEX DEVELOPMENT AND POSTWEANING LEARNING PERFORMANCE IN SHRSP
Authors: Matsuo T. , Kihara T. , Tanimura T.
Published: June 2007

1. Dietary high protein intake in stroke‐prone spontaneously hypertensive rats (SHRSP) induces a reduction of blood pressure and decreases the incidence of cerebral lesion. The objective of this investigation was to determine the effects of nutritional factors of dietary high protein on reproduction, growth, pre‐weaning reflex development, postweaning behaviour and learning performance in SHRSP.

2. SHRSP were fed on a high protein rat diet (OA2 diet) and a standard rat diet for SHRSP (FSP diet). Rats were mated by brother‐sister combinations and observed on reproductive performance, preweaning reflex development and postweaning learning performance among the 3rd to the 6th generations.

3. OA2 showed some advanced responses at the preweaning period compared to FSP in the surface righting, negative geotaxis and mid‐air righting reflexes.

4. At the postweaning period, hyperactivity of OA2 was indicated at the open field test. In the ambulatory activity of the circadian rhythm, OA2 was better synchronized with running activity in the light and dark alternation cycle.

5. OA2 group indicated the higher postweaning learning performance in the water E, the water multiple T (Biel) and the Morris water‐maze test as well as the acquisition of the conditioned avoidance response test.

6. In conclusion, dietary high protein intake in SHRSP produced some advanced effects on preweaning reflex development and postweaning learning performance.
SESAME LIGNANS MODULATE CHOLESTEROL METABOLISM IN THE STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Ogawa Hiroshi , Sasagawa Sukenari , Murakami Tetsuo , Yoshizumi Hazime
Published: June 2007

1. Effects of sesamin and episesamin (an epimer of sesamin) on lipid metabolism, in particular cholesterol metabolism, were examined in normocholesterolaemic and hypercholestero‐laemic stroke‐prone spontaneously hypertensive rats (SHRSP).

2. In normocholesterolaemic SHRSP fed a regular diet, both sesamin and episesamin significantly increased the concentration of serum total cholesterol, which was due to an increase of high density lipoprotein (HDL) subfraction rich in apoE (apoE‐HDL). In addition, both substances effectively decreased serum very low density lipoprotein (VLDL). In the liver, only episesamin significantly decreased the activity of microsomal acyl‐CoA: cholesterol acyltransferase.

3. In hypercholesterolaemic SHRSP fed a high‐fat and high‐cholesterol diet (HFC diet), only episesamin improved serum lipoprotein metabolism with an increase in apoA‐I and a decrease in apoB. In the liver, both sesamin and episesamin significantly suppressed cholesterol accumulation. Interestingly, only episesamin significantly increased the activity of microsomal cholesterol 7α‐hydroxylase.

4. These results indicate that sesamin may be effective in preventing cholesterol accumulation in the liver. In comparison with sesamin, episesamin may be effective in the regulation of cholesterol metabolism in the serum and liver.
EFFECT OF LOVASTATIN AND FLUOROMEVALONATE ON PHOSPHATIDYLINOSITOL 3‐KINASE ACTIVITY STIMULATED WITH PDGF
Authors: Iwama A. , Sawamura M. , Nara Y. , Yamori Y.
Published: June 2007

1. Phosphatidylinositol 3‐kinase (PI3K) appears to have a crucial role in cellular proliferation induced by platelet‐derived growth factor (PDGF). However, the mode of activation of the enzyme has been unclear so far. In the present study, we investigated the effects of a cholesterol lowering drug on [3H]‐thymidine ([3H]‐TdR) incorporation and PI3K activity in cultured vascular smooth muscle cells (VSMC) stimulated with PDGF.

2. PDGF stimulated both [3H]‐TdR incorporation and PI3K activity immunoprecipitated with antiphosphotyrosine antibody in a dose dependent manner (EDSO was 4 ng/mL for [3H]‐TdR uptake and 3 ng/mL for PI3K activity). Lovastatin inhibited serum‐stimulated [3H]‐TdR incorporation dose dependently. PI3K activity induced by PDGF was also inhibited in a dose dependent manner; however, its activity was 61% at 10‐6 mol/L, 72% at 10‐5 mol/L and 8% at 10‐4 mol/L of the control value.

3. These inhibitory effects of lovastatin were completely abolished by adding 1 mmol/L mevalonic acid (MVA), suggesting that MVA metabolites had some important role on the PI3K activation and cellular proliferation.

4. Fluoromevalonate (Fmev), a competitive inhibitor of mevalonate diphosphate (MVA‐PP) decarboxylase, inhibited [3H]‐TdR incorporation at concentrations more than 10‐6 mol/L. Moreover, marked inhibitory effect was observed at concentrations of 10‐7 and 10‐8 mol/L (76% of control). PI3K activity was also reduced by 10‐3 mol/L Fmev (0.2% of control). However, in contrast to [3H]‐TdR uptake, there was no inhibitory effect detected at concentrations up to 10‐4 mol/L.

5. These results suggest that PDGF‐stimulated PI3K activity as well as cellular proliferation was modified by protein isoprenylation.