Biomedical subjects

T Nakata

Publications and source records attributed to T Nakata.

At least 145 records · Page 8Linked to original sources

PubMed1996

GABAB-ergic stimulation in hypothalamic pressor area induces larger sympathetic and cardiovascular depression in spontaneously hypertensive rats.

To determine whether central GABA (gamma-aminobutyric acid) B receptor stimulation would affect the sympathetic and cardiovascular activities, baclofen (a GABAB receptor agonist) was injected into lateral cerebral ventricles (intracerebroventricularly, ICV) in urethane-anesthetized normotensive rats. Intracerebroventricular injections of GABAA agonist (muscimol, 1 microgram) consistently decreased blood pressure and heart rate. In contrast ICV injections of baclofen (2 micrograms) increased blood pressure (BP) and heart rate with initial transient cardiovascular depression, and these effects of baclofen were abolished by ICV pretreatment with GABAB antagonist (saclofen, 100 micrograms). To determine whether the cardiovascular effects of ICV injections were elicited by activating GABA receptors in the hypothalamus, we injected baclofen or muscimol directly into various hypothalamic areas. Baclofen (100 and 800 ng) injected into the ventromedial hypothalamus (VMH) or posterior hypothalamus (PH) of normotensive rats produced dose-related decreases in sympathetic nerve activity, blood pressure, and heart rate. These effects of baclofen were larger in VMH injections than in PH injections. The depressor responses elicited by VMH injections of baclofen were abolished by intravenous pretreatment with alpha-blocker, but unaffected by parasympathetic blocker, further indicating that the depressor responses of baclofen (VMH) were not due to parasympathetic activation, but due to peripheral sympathetic depression. Muscimol (400 ng) and baclofen (800 ng) injected into VMH produced similar amplitude of sympathetic-depressant, depressor and bradycardic responses. In contrast, BP was increased by the same dose of baclofen injected into the hypothalamic depressor area (anterior hypothalamus, AH), but was unaffected by muscimol. Final experiments were performed to determine whether these sympathetic and cardiovascular effects to hypothalamic GABAB stimulations would be altered in hypertension. In spontaneously hypertensive rats (SHR), basal BP and heart rate were already higher than in normotensive controls (Wistar-Kyoto rat, WKY). Baclofen injected into VMH reduced sympathetic nerve activity, BP, and heart rate in both groups of rats, and these effects were significantly larger in SHR than in WKY. This enhanced depressor response induced by baclofen (VMH) in SHR persisted even after sinoaortic denervation, which indicates that the enhanced depressor response is not due to reduced peripheral baroreflex sensitivity in SHR. On the other hand, baclofen injected into AH increased BP and heart rate in both WKY and SHR, but the magnitude of these responses did not differ between two groups. In summary, GABA reduces sympathetic nerve activity, BP, and heart rate through both GABAA and B receptors in VMH. The GABAB system acts on the depressor area, AH, to further regulate the cardiovascular activities. In SHR, the GABAB-ergic system in VMH but not in AH is altered, and this might contribute to the development of hypertension.

Animals↗

PubMed1996

mRNA expression of KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, KIF5, and cytoplasmic dynein during axonal regeneration.

Mouse brain expresses multiple kinesin superfamily proteins (KIFs), which are involved in vesicle transport. The expression of KIFs is developmentally regulated, and both the mRNA and proteins of KIF2 and KIF4 are expressed abundantly in the juvenile brain. To elucidate the role of individual kinesin superfamily motor proteins during regenerative outgrowth of axons, we examined the mRNA expression of KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, and KIF5 in adult mouse dorsal root ganglion cells after sciatic nerve crush. Seven to fourteen days after the nerve crush, the mRNA expression pattern of neurofilament and beta-tubulin isotypes suggested that the regenerative outgrowth of axons was active. At these stages, levels of mRNA for KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, and KIF5 were 50.80% of control. The levels of mRNA for KIF4, which are detected in juvenile brain but not in the adult, were under the detection limit in both control and regenerating dorsal root ganglion cells. Because mRNA of neither KIF2 nor KIF4 increased significantly, the results suggest that the gene expression of KIFs during regeneration does not recapitulate the embryonic development and support the hypothesis that different series of events take place during the regenerative and embryonic outgrowths of axons. In contrast, mRNA for cytoplasmic dynein was slightly increased, up to 140%. This is consistent with the hypothesis that retrograde transport plays critical roles in regeneration such as the transport of neurotrophic factors.

Age Factors↗

PubMed1996

Blood pressure at health screening as a predictor of coronary heart disease in Kyoto.

AIM: Most epidemiologic studies that have evaluated coronary risk factors have measured either mortality or morbidity of coronary artery disease (CAD) as endpoints. However, earlier detection and elimination of coronary risk factors are crucial. We therefore performed Master's double (i.e. 1.5 min x 2 = 3 min) two-step exercise electrocardiograph (ECG) test in apparently healthy asymptomatic subjects (men, n = 2274; women, n = 959) to elucidate the risk factors for early-stage CAD or silent myocardial ischemia. METHODS: We examined the possible association of blood pressure at health screening and other suspected risk factors with exercise ECG test performance. The ischemic ECG response was determined by (1) > or = 0.5 mm horizontal or sagging S-T segment depression, (2) > or = 2.0 mm J-shaped S-T segment depression, or (3) T inversion in post-exercise ECG. RESULTS: We found that 4.7% of men and 10.6% of women exhibited ischemic responses. Among males, the ischemic responders to the exercise ECG test had higher systolic and diastolic blood pressure. In addition, the male ischemic responders were older, had a higher obesity index, higher serum cholesterol, triglyceride, low-density lipoprotein (LDL)-cholesterol, protein, glucose, and uric acid levels, and a lower serum potassium level than normal responders. In contrast, the female ischemic responders to the exercise ECG test had higher systolic pressure, and higher serum cholesterol, LDL-cholesterol, and protein levels than normal responders. Mean blood pressure was correlated positively with most of the other coronary risk factors, and mild hypertensives and hypertensives had abnormal lipid, glucose, and uric acid levels in both sexes. A comparison of risk factors by age group revealed that only younger and middle-aged ischemic responders had higher blood pressure, serum cholesterol, and glucose levels than normal responders of both sexes, and that in older subjects all the differences between normal and ischemic responders became insignificant. CONCLUSIONS: Elevated blood pressure at health screening, together with abnormal lipid and glucose metabolism, might be risk factors predicting early-stage or silent CAD. The elimination of these risk factors in younger men and women seems to be important.

Adult↗

PubMed1996

[Natural killer cell lymphoma having a nodular shadow in the lung as an initial finding, developed to leukemia complicated with hemophagocytic syndrome at the time of relapse].

A 57-year-old female was admitted to Uji hospital for the further evaluation of nodular shadow on her right lung. During the period of admission, she developed cervical lymph node swelling. She was diagnosed as having malignant lymphoma (diffuse, small cleaved cell) by lymph node biopsy. She received combined chemotherapy and obtained partial remission for seven months until she developed fever and pancytopenia. Laboratory data showed increased number of large granular lymphocytes (LGLs) in blood. Bone marrow revealed increased number of LGLs with hemophagocytosis by macrophage. Surface marker analysis revealed LGLs were positive for CD2 CD16, and CD56 and negative for CD3, CD4, CD8, and CD20. T-cell receptor genes beta and gamma were in germ line configuration. Analysis of Epstein-Barr virus genome using termini probe indicated a monoclonal proliferation of LGLs. Reexamination of the biopsy specimen of lymph node revealed LGLs which was negative for CD3 and CD20. The patient was diagnosed as a leukemic phase of natural killer (NK) cell lymphoma complicated with hemophagocytic syndrome (HPS). Serum levels of interferon-gamma, macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-6 increased, which might be related to HPS.

Antigens, CD↗

PubMed1996

[The perinatal risk factors and periventricular leukomalacia (PVL) in premature infants--relationship between fetal heart rate decelerations and PVL].

Periventricular leukomalacia (PVL) has recently been recognized as an important risk factor of neurological impairment in premature infants. We studied 29 PVL cases on perinatal risk factors comparing with a non-PVL matched control group retrospectively. Variable decelerations were more frequently observed with statistical significance in the PVL group in the intrapartum period. Then another study was conducted to evaluate the relationship between fetal heart rate (FHR) decelerations and cystic PVL prospectively. Since January 1993 through December 1994 we studied 209 low birth weight infants (31.1 +/- 3.2 weeks, 1,424 +/- 419 g) who had been subjected to intrapartum FHR monitoring and postnatal sonographic intracranial examinations sequentially every 7 days until discharge. Cystic PVL was detected in 6 of 209 cases (2.9%) and occurred only in infants who had revealed severe variable deceleration or prolonged deceleration (6/37, 16%) in intrapartum FHR monitoring. We conclude that in low birth weight infants intrapartum severe variable deceleration or prolonged deceleration might play a causal role in cystic PVL.

Bradycardia↗

PubMed1996

Detection of impaired fatty acid metabolism and dyskinesis in hypertrophic cardiomyopathy with iodine-123-BMIPP.

Metabolic imaging using 123I-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) and Fourier phase analysis of gated blood-pool data were performed in a 60-yr-old woman with idiopathic hypertrophic cardiomyopathy. Dyskinetic wall motion was identified as a markedly delayed phase angle in the left ventricular apex, which was well perfused but highly hypertrophied like other ventricular segments. Fatty acid imaging, however, clearly demonstrated highly reduced activities in the apex, although there were no abnormalities in regional systolic function or in 201TI uptake in other hypertrophied regions. Contrast left ventriculography revealed a midventricular collapse of the left ventricle at end-systole due to markedly hypertrophied ventricular walls and dyskinesis at the apex. Thus, dyskinetic wall motion in the apex closely correlated not only with cardiac hypertrophy but also with impaired fatty acid uptake. These findings were unrelated to the myocardial perfusion state per se. Fatty acid imaging using BMIPP may contribute to the detection of myocyte degeneration not visible using conventional imaging modalities. It may also provide etiological information on regional dysfunction in hypertrophic cardiomyopathy.

Cardiomyopathy, Hypertrophic↗

PubMed1996

[Successful removal of an infected pacemaker electrode, drifted into the right atrium, by using a lead removal kit].

A 65-year-old male was suffered complications from an infected pacemaker in the left subclavian region. The generator was removed and its electrode was cut at the vascular entry. A new system was implanted on the other side. Two months later, he suffered from persistent fever which required administration of antibiotics for 2 months. 7 months later, the cut end of the infected electrode was found to have drifted into the right atrium. Its removal was performed to prevent a potential exacerbation of the systemic infection. We were able to pick up an end of the electrode using a basket catheter which was inserted through the right internal jugular vein to extract it. The lead was then successfully removed using a lead removal kit.

Aged↗

PubMed1995

Young borderline hypertensives are hyperreactive to mental arithmetic stress: spectral analysis of R-R intervals.

To investigate whether sympathetic tone and its reactivity to stress are increased in borderline hypertension, we compared pressor and autonomic nervous responses to mental arithmetic stress in male borderline hypertensives (BH) and normotensive volunteers (NT). Three age groups, 30, 40 and 50-year-old groups, which included 30 to 39, 40 to 49 and 50 to 59-year-old subjects, were studied. Fractional LF (%LF), fractional HF (%HF) and L/H, obtained from the power spectrum of R-R intervals, were used as indices of autonomic nervous function. Baseline autonomic nervous indices did not differ between NT and BH of any age group. Blood pressure rose higher during mental arithmetic stress in 50 than in 30-year-old NT but not in comparable age groups of BH. Pressor responses were augmented in BH compared to NT only in the 30-year-old group. However, the differences were not significant when pressor responses were expressed as percent increases in blood pressure. Both %L and L/H increased during arithmetic stress. The increase in %L did not differ between NT and BH but that in L/H (% delta L/H) was larger in 50 than in 30-year-old NT. % delta L/H was larger in BH than in NT only in the 30-year-old group. These findings suggest that both pressor and autonomic nervous responses to metal arithmetic stress were altered by aging and augmented in BH compared to NT in the 30-year-old group.

Adult↗

PubMed1995

The functional role of 55- and 75-kDa tumour necrosis factor receptors in human polymorphonuclear cells in vitro.

The expression and biological role of 55- and 75-kDa tumour necrosis factor-receptors (TNF-RI and TNF-RII) in human polymorphonuclear cells (PMN) in vitro were studied using agonistic rabbit polyclonal anti-TNF-R antibodies. PMN express TNF-RII predominantly, and release the superoxide anion on stimulation by human recombinant lymphotoxin (LT) in vitro. Anti-TNF-RI but not anti-TNF-RII antibody stimulated the superoxide release mimicking LT. Release of the elastase from azurophilic granule of PMN was augmented by LT in vitro. Anti-TNF-RI but not anti-TNF-RII antibody augmented the elastase release. Release of the lactoferrin from the specific granules of PMN was enhanced by LT in vitro. Anti-TNF-RI but not anti-TNF-RII antibody augmented the elastase release. Release of the lactoferrin from the specific granules of PMN was enhanced by LT in vitro. Anti-TNF-RI but not anti-TNF-RII antibody enhanced the lactoferrin release. These antibodies failed to co-stimulate these PMN functions. The adhesiveness of PMN to a plastic plate and the expression of Mac-1 on PMN were upregulated by LT in vitro. Anti-TNF-RI but not anti-TNF-RII antibody upregulated the adhesiveness and Mac-1 expression of PMN mimicking LT. Though anti-TNF-RII antibody by itself did not alter the adhesiveness and marginally suppressed Mac-1 expression, it maintained the adhesiveness and adhesion molecule expression in the presence of anti-TNF-RI antibody. In summary, PMN predominantly express TNF-RII, the signalling of LT (and TNF) in PMN is mediated mainly by TNF-RI, and the adhesion function can be modulated also by TNF-RII when TNF-RI is stimulated.

Antibodies↗

PubMed1995

Splenic metastasis from lung cancer.

Splenic metastasis from lung cancer is a rare clinical event, most often diagnosed at the time of autopsy. We report 2 cases of splenic metastasis with a primary lung cancer. The first case was a 76-year-old man presenting with a recurrent solitary splenic metastasis 14 months after surgical removal of a squamous cell carcinoma of the lung. The second patient was a 72-year-old woman who had a poorly differentiated carcinoma of the lung and multiple abdominal metastasis. We also investigated 267 autopsy cases of lung cancer from 1975 to 1992. Histologically, there were 73 cases of squamous cell carcinoma, 123 adenocarcinoma, 29 large cell carcinoma, 36 small cell carcinoma, and 7 other miscellaneous tumours. The number of splenic metastasis from lung cancer in these cases was 15 (5.6%). Splenic metastasis from a primary cancer of the left lung was more frequent than that from the right lung. Nine of 15 splenic metastases were smaller than 1 cm in size. Splenic metastasis was associated with liver and pancreas metastasis. All 15 autopsy cases with splenic metastasis from lung cancer had other abdominal organ metastasis. Our analysis indicates that a solitary splenic metastasis is rare. Selection of a suitable therapeutic approach is important.

Aged↗

PubMed1995

KIF3A/B: a heterodimeric kinesin superfamily protein that works as a microtubule plus end-directed motor for membrane organelle transport.

We cloned a new member of the murine brain kinesin superfamily, KIF3B, and found that its amino acid sequence is highly homologous but not identical to KIF3A, which we previously cloned and named KIF3 (47% identical). KIF3B is localized in various organ tissues and developing neurons of mice and accumulates with anterogradely moving membranous organelles after ligation of nerve axons. Immunoprecipitation assay of the brain revealed that KIF3B forms a complex with KIF3A and three other high molecular weight (approximately 100 kD)-associated polypeptides, called the kinesin superfamily-associated protein 3 (KAP3). In vitro reconstruction using baculovirus expression systems showed that KIF3A and KIF3B directly bind with each other in the absence of KAP3. The recombinant KIF3A/B complex (approximately 50-nm rod with two globular heads and a single globular tail) demonstrated plus end-directed microtubule sliding activity in vitro. In addition, we showed that KIF3B itself has motor activity in vitro, by making a complex of wild-type KIF3B and a chimeric motor protein (KIF3B head and KIF3A rod tail). Subcellular fractionation of mouse brain homogenates showed a considerable amount of the native KIF3 complex to be associated with membrane fractions other than synaptic vesicles. Immunoprecipitation by anti-KIF3B antibody-conjugated beads and its electron microscopic study also revealed that KIF3 is associated with membranous organelles. Moreover, we found that the composition of KAP3 is different in the brain and testis. Our findings suggest that KIF3B forms a heterodimer with KIF3A and functions as a new microtubule-based anterograde translocator for membranous organelles, and that KAP3 may determine functional diversity of the KIF3 complex in various kinds of cells in vivo.

Amino Acid Sequence↗

PubMed1995

Point mutation of adenosine triphosphate-binding motif generated rigor kinesin that selectively blocks anterograde lysosome membrane transport.

In the study of motor proteins, the molecular mechanism of mechanochemical coupling, as well as the cellular role of these proteins, is an important issue. To assess these questions we introduced cDNA of wild-type and site-directed mutant kinesin heavy chains into fibroblasts, and analyzed the behavior of the recombinant proteins and the mechanisms involved in organelle transports. Overexpression of wild-type kinesin significantly promoted elongation of cellular processes. Wild-type kinesin accumulated at the tips of the long processes, whereas the kinesin mutants, which contained either a T93N- or T93I mutation in the ATP-binding motif, tightly bound to microtubules in the center of the cells. These mutant kinesins could bind to microtubules in vitro, but could not dissociate from them even in the presence of ATP, and did not support microtubule motility in vitro, thereby indicating rigor-type mutations. Retrograde transport from the Golgi apparatus to the endoplasmic reticulum, as well as lysosome dispersion, was shown to be a microtubule-dependent, plus-end-directed movement. The latter was selectively blocked in the rigor-mutant cells, although the microtubule minus-end-directed motion of lysosomes was not affected. We found the point mutations that make kinesin motor in strong binding state with microtubules in vitro and showed that this mutant causes a dominant effect that selectively blocks anterograde lysosome membrane transports in vivo.

Adenosine Triphosphate↗

PubMed1995

Correlations of antimyosin accumulation and histological manifestation of myocyte necrosis at different stages of idiopathic cardiomyopathy.

Although antimyosin uptake has been demonstrated in idiopathic cardiomyopathy, discrepancies between antimyosin positivity and histological examinations using biopsy speciments have been found. In order to investigate the correlations between antimyosin localization and histopathological alterations, the magnitude and distribution of antimyosin uptake were quantitatively assessed in aged-matched control (F1b) and hereditary idiopathic cardiomyopathy (Bio 14.6) hamsters at three different ages. In these studies, gamma counting and macroautoradiography were compared with histological alterations. Myocardial activities and percent areas of antimyosin uptake were significantly (P<0.05) greater in 10-, 20-, and 30-week old Bio groups than in their respective control groups. Autoradiograms showed that antimyosin antibody was relatively localized, massive, and scattered in 10-week-old, 20-week-old and 30-week-old Bio hamsters, respectively. Histopathology demonstrated antimyosin positivity not only in necrotic myocytes and accompanying calcium deposits but also in tissues showing inflammatory reactions but no histologically identifiable myocyte necrosis. In conclusion, antimyosin uptake seen in tissues with age-related disease processes did not necessarily correspond to histologically verified myocyte necrosis in the cardiomyopathy hearts, suggesting that antimyosin positivity reflects myocytes which show impaired sarcolemmal integrity but have not yet undergone myolysis.

Animals↗

PubMed1995

Altered cardiovascular responses to purinergic A2 stimulation in the nucleus tractus solitarius of spontaneously hypertensive rats.

OBJECTIVE: To investigate the cardiovascular effects of adenosine A2 receptor stimulation in the nucleus tractus solitarius and whether these effects are altered in hypertension. DESIGN AND METHODS: Ten- or 11-week-old spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats were anaesthetized with urethane. Adenosine (100 ng) or adenosine A2 agonist (2-octynyladenosine, 5 ng) were micro-injected (50 nl) into the nucleus tractus solitarius. Blood pressure and heart rate were measured from a femoral artery. Sympathetic nerve activity was recorded from the abdominal splanchnic nerve. RESULTS: Blood pressure, heart rate and sympathetic nerve activity were consistently decreased after the micro-injection of adenosine into normotensive rats. Changes from the baseline in blood pressure, heart rate and sympathetic nerve activity were significantly smaller in SHR than in WKY rats (blood pressure: SHR -5.6 +/- 2.1% versus WKY rats -20.0 +/- 2.1%; heart rate: SHR -5.4 +/- 0.88% versus WKY rats -9.2 +/- 2.3%; sympathetic nerve activity: SHR -5.5 +/- 1.1% versus WKY rats -21 +/- 2.8%). Micro-injection of an A2 agonist into the nucleus tractus solitarius also decreased blood pressure and heart rate, and those responses were not inhibited by pretreatment with an adenosine A1-specific antagonist. The response induced by micro-injection of A2 agonist into the nucleus tractus solitarius was significantly smaller in SHR than in WKY rats, whereas the changes in heart rate did not differ statistically (blood pressure: -23.4 +/- 4.7% versus -10.8 +/- 2.1%; heart rate: -12.1 +/- 1.2% versus -13.6 +/- 2.1%). CONCLUSION: The present results suggest that stimulation of adenosine A2 receptors in the nucleus tractus solitarius decreases both blood pressure and inhibitory sympathetic nerve activity and that those inhibitory responses to adenosine in the nucleus tractus solitarius are deranged in SHR.

Adenosine↗

PubMed1995

Role of nitric oxide in impaired coronary circulation and improvement by angiotensin II receptor antagonist in spontaneously hypertensive rats.

1. To determine whether coronary flow regulation by nitric oxide (NO) is impaired in the hypertensive heart (HTH), coronary perfusion was measured in isolated rat hearts using NO synthesis inhibitor L-NG-monomethyl arginine (L-NMMA) in Wistar-Kyoto (WKY) rat and spontaneously hypertensive rat (SHR) with and without chronic Nomega-nitro-L-arginine-methylester (L-NAME) treatment. Moreover, the effect of angiotensin II receptor antagonist (AT1 receptor antagonist) (TCV-116) on the impaired coronary circulation in HTH was examined. 2. Coronary flow (CF) was decreased in HTH accompanied with cardiac hypertrophy. The decreased response of CF to L-NMMA infusion was diminished in HTH. It is suggested that NO production was reduced in coronary vasculature in HTH. 3. In chronic L-NAME treated SHR, blood pressure and cardiac hypertrophy were accelerated. Although coronary flow resistance (CFR) was increased, the increased response of CFR to L-NMMA infusion was not altered. 4. The AT1 antagonist improved total minimal coronary flow resistance (MCFR) restoring CFR response in SHR, although it did not recover CFR response in chronic L-NAME treated SHR. 5. Taken together the findings suggest that NO production was exhausted in the coronary artery even in the developing stage of hypertension and this exhaustion could contribute to the impairment of coronary circulation of HTH.

Angiotensin II↗

PubMed1995

Differences in the characterization of the Ca2+ current in ventricular myocytes between spontaneously hypertensive rats and normotensive rats.

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 +/- 0.2 pA. 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 0 mV, -2.1 +/- 0.8 pA at -10 mV and -4.4 +/- 0.3 pA at -20 mV. 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(-6) mol/L increased the Ca2+ current in SHR and WR. The increased ratio of Ca2+ current by l-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 Ca2+ channel being activated by phosphorylation through cAMP did not eventuate.

Adrenergic beta-Agonists↗

PubMed1995

Effects of gamma-linolenic and eicosapentaenoic acids on blood pressure in SHR.

1. The present study was performed to determine whether chronic treatments with gamma linolenic acid (n-6, GLA) or eicosapentaenoic acid (n-3, EPA) would alter serum and red blood cell (RBC) unsaturated fatty acid composition, and to determine whether these treatments would affect blood pressure (BP), serum lipid metabolism and the development of atherosclerosis in spontaneously hypertensive rats (SHR). 2. To compare the effects on atherosclerosis, some SHR were denuded of aortic endothelium so that the development of atherosclerosis would be accelerated. Olive oil (control), GLA or EPA (low dose: 5 mg/day per rat, high dose: 50 mg/day per kg, respectively) was administered intraperitoneally for 6 weeks in SHR. 3. GLA treatments increased GLA and its metabolite, dihomo-GLA, levels in serum but not in RBC, while EPA treatments increased EPA level both in serum and in RBC. 4. The BP of control SHR was further elevated. EPA significantly reduced this elevation of systolic, mean and diastolic pressure within the first week and thereafter, whereas GLA did not affect BP elevation. Neither heart rate or bodyweight gain was affected by these treatments. 5. Serum total cholesterol (TC), triglyceride (TG), and glucose (G) levels and the development of atherosclerosis were unaffected by either GLA or EPA treatment. 6. In summary, chronic EPA but not GLA treatment slightly reduced BP elevation in SHR. Although chronic GLA or EPA treatment increased the respective serum level, these treatments unaltered serum TC, TG and G levels, and could not prevent the development of aortic atherosclerosis in SHR.

Animals↗

PubMed1995

Hypothalamic and medullary GABAA and GABAB-ergic systems differently regulate sympathetic and cardiovascular systems.

1. 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. Intracerebroventricular (ICV) injections of a GABAA agonist (muscimol, 1 mu g) decreased blood pressure (BP) and heart rate (HR). ICV injections of baclofen (2 mu g) elicited biphasic depressor and pressor effects, and these effects were abolished by a pretreatment with saclofen (GABAB antagonist, 100 mu g, 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 sympatho-inhibitory 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.

Animals↗