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Volume 69 (1995)
- Issue 4 Pages 293-
- Issue 3 Pages 181-
- Issue 2 Pages 75-
- Issue 1 Pages 1-
Volume 69, Issue 2
Displaying 1-14 of 14 articles from this issue
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Fujiko Sanae, Shinji Ohmae, Mariko Kurita, Hiroyuki Sawanishi, Kenzo T ...1995 Volume 69 Issue 2 Pages 75-82
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSRelationships between the alkyl substitutions (C1-C6) and cardiac inotropic activities of xanthine derivatives were studied in isolated guinea pig heart muscles. Most of the alkylxanthines exhibited positive inotropic activity on the left atrium, which was increased with an elongation of alkyl chain at the N3-position but decreased by substitution of a long alkyl group at the N1- or N7-position of the xanthine skeleton. Although positive inotropic activity in the right ventricular papillary muscle was also increased by longer alkyl groups at the N3-position, the inotropic activity became negative with an increment in alkyl chain length at the N1- or N7-position. The positive inotropic activity of alkylxanthines was correlated with their inhibitory activity on the phosphodiesterase (PDE) III isoenzyme. Adenosine A1 antagonism and PDE IV inhibitory activity were also partly associated with the inotropic activity because H-89, an inhibitor of cyclic AMP-dependent protein kinase, diminished the positive inotropic action and potentiated the negative inotropic action. These results indicate that the positive inotropic activity of alkylxanthines becomes weak with elongation of alkyl chains at the Nl- and N7-positions; In particular, xanthines having two long alkyl chains show a negative inotropic activity on the right ventricular papillary muscle, an effect that could not be elucidated from their cyclic AMP-dependent action.View full abstractDownload PDF (491K) -
Iturou Ida, Takayasu Asami, Hisashi Kuribara1995 Volume 69 Issue 2 Pages 83-90
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSAlterations of cocaine effects, which were induced by prior repeated 5-time administration of MK-801 ((+)-5-methyl-10, 11-dihydro-5H-dibenzo[a, d]cyclohepten-5, 10-imine) (i.p.) alone or in combination with cocaine (s.c.) at 3- to 4-day intervals, were investigated by means of ambulatory activity in mice. The repeated administration of either cocaine (10 and 20 mg/kg) alone or MK-801 (0.3 mg/kg) alone progressively enhanced each drug''s effect. The enhanced effects of cocaine and MK-801 were estimated to be 1.8-2.2 times and about 1.4 times, respectively, as great as those at the 1st administration. Although the coadministration of MK-801 with cocaine produced a significant enhancement in the ambulation-increasing effect, the comparatively higher doses of MK-801 (0.3 and 1 mg/kg) acted not only to reduce cocaine sensitivity but also to inhibit the development of cocaine sensitization. Thus, the mice that had been given MK-801 (0.3 and 1 mg/kg) alone 5 times showed lower sensitivities to cocaine (20 mg/kg) than the mice given saline alone. The mice coadministered MK-801 (0.3 and 1 mg/kg) with cocaine (10 and 20 mg/kg) also exhibited lower sensitivities to cocaine (10 and 20 mg/kg) than those given cocaine alone. However, MK-801 could not ameliorate the established sensitization to cocaine. Similar interactions have been demonstrated between MK-801 at 1 mg/kg, but not 0.3 mg/kg, and methamphetamine. The present results indicate that MK-801 can inhibit the development of sensitization to cocaine at a lower dose than that required to inhibit methamphetamine sensitization.View full abstractDownload PDF (513K) -
Susumu Okabe, Kenichi Shimosako, Hiroyuki Harada1995 Volume 69 Issue 2 Pages 91-100
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSLeminoprazole, an acid pump inhibitor, significantly reduces basal and stimulated gastric acid secretion in rats when administered via the systemic or local route. Our aim here was to characterize the antisecretory effect of leminoprazole on gastric acid secretion in conscious dogs. Gastric acid secretion by dogs with a vagally denervated Heidenhain pouch was stimulated by intravenous histamine infusion. Leminoprazole or omeprazole (as a reference drug) was administered either intravenously or locally into the pouch before or after histamine infusion. A bolus intravenous administration of leminoprazole and omeprazole, respectively, significantly and dose-relatedly inhibited the stimulated gastric acid secretion for ›26 hr. Local application of leminoprazole, but not omeprazole, significantly inhibited the acid secretion when applied for 15 to 30 min. The duration of the local antisecretory effect observed after 30 min application was around 8 -10 hr. The acid-degraded products of leminoprazole had no effect when applied to the pouch. The blood concentration of leminoprazole was very low at 1 hr after local application. These results indicate that leminoprazole suppresses the secretory function of the parietal cells of dogs, via both the intravenous and local routes. It remains unknown whether or not locally applied leminoprazole produced the acid inhibition by inhibiting the acid pump.View full abstractDownload PDF (541K) -
Masaki Kitahara, Kyomi Toyoda, Toshie Yamashita, Mitsuaki Sakashita, S ...1995 Volume 69 Issue 2 Pages 101-109
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSThe effects of efonidipine hydrochloride (efonidipine), a dihydropyridine calcium antagonist, on the cholesterol ester metabolism induced by beta-migrating very low density lipoprotein (β-VLDL) in J774 macrophages were studied. The cholesteryl ester content in the macrophages was increased by incu-View full abstractDownload PDF (622K) -
Takashi Murata, Yukio Matsumoto, Tatsuo Kashida, Osamu Kaminuma, Kazua ...1995 Volume 69 Issue 2 Pages 111-118
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSWe investigated the effect of imidapril, a novel angiotensin-converting enzyme (ACE) inhibitor, on augmentation of airway microvascular leakage induced by bradykinin (BK) and substance P (SP) in guinea pigs and compared it with those of enalapril and captopril. The three ACE inhibitors significantly potentiated BK- and SP-induced airway microvascular leakage in a dose-dependent manner. In spite of the compatible or higher ACE inhibitory activity of imidapril, its potentiating activity in BK-induced leakage was lower than those of enalapril and captopril both by single administration (0.3-30 mg/kg, p.o.) and repeated administration for eight days (0.1-10 mg/kg/day, p.o.). The potentiating activities of the three ACE inhibitors were suppressed by pretreatment with a BK2-receptor antagonist, but not by neurokinin 1 and neurokinin 2 antagonists, suggesting that neurokinins may not be involved in BK-induced leakage under the conditions used. On the other hand, the potentiating effect of imidapril in SP-induced leakage was weaker than those of enalapril and captopril only after single high doses. The present study shows that the ACE inhibitors have different activity in potentiation of the airway microvascular leakage induced by BK, which may be ascribable to the difference in their inhibition of BK hydrolysis. This evidence may partly explain the smaller incidence of dry cough induced by imidapril compared with other ACE inhibitors when clinically used as antihypertensive drugs.View full abstractDownload PDF (517K) -
Masahiro Hosono, Tohru Hiruma, Kiyoshi Watanabe, Yutaka Hayashi, Haruo ...1995 Volume 69 Issue 2 Pages 119-125
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSWe investigated the effect of cilnidipine on cardiovascular and neuroendocrine responses to acute cold stress in conscious and unrestrained or moderately restrained spontaneously hypertensive rats (SHRs). Acute cold stress significantly increased mean blood pressure without marked change in heart rate. The acute cold stress-induced elevation in blood pressure was almost abolished by 1 mg/kg, p.o. of prazosin. The cold stress also elevated plasma norepinephrine and epinephrine levels. Cilnidipine at 3 mg/kg, p.o. significantly inhibited the pressor response to acute cold stress. Although 3 mg/kg, p.o. of nifedipine, nicardipine or manidipine lowered mean blood pressure to a similar extent as cilnidipine, none of these three drugs affected the pressor response. Cilnidipine also reduced the cold stress-induced increment in plasma norepinephrine but not the epinephrine level. These findings suggest that acute cold stress may induce the elevation in blood pressure due to an enhanced activation of the sympathoadrenal system in SHRs and that cilnidipine may suppress the pressor response by inhibiting the sympathetic nerve activity.View full abstractDownload PDF (457K) -
Masahiro Hosono, Shigeo Fujii, Tohru Hiruma, Kiyoshi Watanabe, Yutaka ...1995 Volume 69 Issue 2 Pages 127-134
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSWe reported previously that cilnidipine inhibited increases in blood pressure and plasma norepinephrine (NE) level in response to cold stress in spontaneously hypertensive rats (SHRs). In the present study, we investigated the effect of cilnidipine on sympathetic neurotransmission and subsequent vasoconstriction in SHRs. In pithed SHRs, electrical sympathetic nerve stimulation (ESNS) elevated blood pressure, and this pressor response was abolished by guanethidine. Cilnidipine at 10 μg/kg, i.v. and phentolamine at 1 mg/kg, i.v. suppressed the pressor response to ESNS by 28 ± 6% and 67 ± 3 %, respectively. Neither nifedipine nor nicardipine inhibited it. The pressor response to exogenous NE was not influenced by cilnidipine. α, β-Methylene ATP inhibited the pressor response to ESNS in the presence or absence of phentolamine. Cilnidipine also attenuated the phentolamine-resistant pressor response to ESNS. In SHR mesenteric vasculatures preloaded with [3H]-NE, cilnidipine (10-7 M) as well as ω-conotoxin significantly inhibited the 3H overflow evoked by periarterial nerve stimulation. In radioligand binding experiments, cilnidipine inhibited [125I]-ω-conotoxin binding to rat synaptosomes, but it did not inhibit [3H]-prazosin binding to rat cortex membranes. These results suggest that cilnidipine may reduce electrically stimulated NE release from the sympathetic nerve endings of SHR vasculatures probably through its N-type Ca channel blocking action and that cilnidipine may also inhibit the vasoconstriction induced by ATP released concomitantly during nerve stimulation.View full abstractDownload PDF (581K) -
Gen Kudo, Naofumi Ohgushi, Minoru Shimoda, Ei-ichi Kokue1995 Volume 69 Issue 2 Pages 135-141
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSOral co-administration of folic acid (pteroylglutamic acid, PteGlu) potentiates the decrease of plasma 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu) concentration induced by pyrimethamine (PYR) in rats. To clarify the mechanisms of this potentiated decrease, we examined the effects of PteGlu and PYR on intestinal absorption of folates in rat jejunum loops, because plasma 5-CH3-H4PteGlu concentration is maintained by enterohepatic circulation of folates. The intestinal absorption of 5-[14C]CH3-H4PteGlu was inhibited by PteGlu, but not by PYR. The absorption of [3H]PteGlu was inhibited by reduced folates that exist in bile. These findings indicate that PteGlu competes with the bile reduced folates for the intestinal transport system. The bile secretion of reduced folates was also examined to observe the conversion of absorbed PteGlu to reduced folates in the liver in the presence of PYR. The bile secretion of reduced folates increased drastically after the administration of PteGlu alone, but not after the administration of PteGlu with PYR. These facts suggest that the absorbed PteGlu was not converted to reduced folates in the liver due to PYR. In conclusion, the potentiated decrease of plasma 5-CH3-H4PteGlu concentration must have resulted from a combination of the following two factors: the inhibition of reabsorption of bile reduced folates by PteGlu and the inhibition of PteGlu conversion to reduced folates in the liver by PYR.View full abstractDownload PDF (536K) -
Hiroshi Kawai, Kazuo Umemura, Mitsuyoshi Nakashima1995 Volume 69 Issue 2 Pages 143-148
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSIschemic cerebral infarcts induce hypercoagulation and microthrombosis in the surroundingView full abstractDownload PDF (767K) -
Masataka Majima, Keiichi Adachi, Yoshikazu Kuribayashi, Susumu Mizogam ...1995 Volume 69 Issue 2 Pages 149-158
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSKininogen-deficient Brown Norway Katholiek (deficient BN-Ka) rats excreted a small amount of kinin in their urine, compared with normal BN Kitasato (normal BN-Ki) rats from the same strain. Intra-arterial (i.a.) infusion (6 ml/kg/hr) of conscious deficient BN-Ka rats with 0.15 M NaCI did not increase mean arterial blood pressure (MBP) [from 103 ± 2 (pre) to 93 ± 6 mmHg (day 4)] and did not cause sodium accumulation in the serum, cerebrospinal fluid or erythrocytes, but 0.3 M NaCI infusion significantly increased MBP from 104 ± 3 (pre) to 130 ± 5 mmHg (day 4) with increased sodium levels in the serum, cerebrospinal fluid and erythrocytes. Infusion of 0.3 M NaCI in normal BN-Ki rats neither increased MBP nor accumulated sodium. The dose-response curve of the increase in MBP for angiotensin II injection (i.a., bolus, 1-1000 pmol/kg) in 0.3 M NaCI-infused deficient BN-Ka rats shifted to the left by a factor of 10 compared with that in 0.15 M NaCI-infused deficient BN-Ka rats, and that for norepinephrine injection shifted to the left by a factor of 30. Normal BN-Ki rats did not show any enhancement in MBP elevation with 0.3 M NaCI. These results suggest that the sodium accumulation attributable to a lack of kinin generation may be related to increased vascular reactivity to angiotensin II and norepinephrine.View full abstractDownload PDF (682K) -
Hideaki Sada, Takashi Ban, Takeshi Fujita, Yoshio Ebina, Nicholas Sper ...1995 Volume 69 Issue 2 Pages 159-166
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSTo assess the age-related changes in kinetic properties of the cardiac Na+ channel, whole-cell voltage-clamp (v-c) experiments were conducted using 3-, 10- and 17-day-old embryonic chick ventricular heart cells. In line with the first-order kinetic model, kinetic parameters for the activation and inactivation of the channel were determined from the v-c results. Simulation studies using kinetic parameters so determined have reproduced the current-voltage relations and the steady-state inactivation characteristics observed in cells in the three age groups. The rate of depolarization of the simulated action potentials was also comparable to that experimentally recorded. In conclusion, the steady-state Na+ conductance can play a significant role in the automatic depolarizations observed in young embryonic ventricular cells.View full abstractDownload PDF (460K) -
Yoshinori Goto, Kazutaka Maeyama1995 Volume 69 Issue 2 Pages 167-171
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSEffects of carbachol and antigen (dinitrophenylated bovine serum albumin) on histamine release and histidine decarboxylase (HDC, the enzyme synthesizing histamine) activity were studied in 2H3-ml cells, a subclone of rat basophilic leukemia cells that expresses human muscarinic ml receptors through transfection with the gene. Carbachol stimulated the release of histamine and the activity of HDC with 30-50% the intensity of the maximal effect of the antigen. Pirenzepine, an ml antagonist, inhibited these carbachol effects in a dose-dependent manner. The effect of the combination of carbachol and antigen on histamine release showed no additivity. These results indicate that these effects of carbachol are exerted via ml receptors, and they suggest that the actions of carbachol and antigen on histamine release share a common pathway(s), and the release and synthesis of histamine have a positive relationship like in a feedback system.View full abstractDownload PDF (339K) -
Takahide Nomura, Masatsugu Ohtsuki, Toshiko Watanabe, Seiko Hasegawa, ...1995 Volume 69 Issue 2 Pages 173-176
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSWe examined the metabolic effects of glibenclamide, a potent second-generation sulfonyl-View full abstractDownload PDF (274K) -
Fu-Yu Chueh, Ming-Tsuen Hsieh, Chieh-Fu Chen, Mao-Tsun Lin1995 Volume 69 Issue 2 Pages 177-180
Published: 1995
Released on J-STAGE: April 07, 2006
JOURNAL FREE ACCESSIn anesthetized rats, intravenous administration of dl-tetrahydropalmatine (dl-THP, 1-10 mg/kg) elicited proportional hypotension, bradycardia and decreases in hypothalamic serotonin (5-HT) release (measured by carbon-fiber electrodes in combination with voltammetry). In addition, postsynaptic blockade of 5-HT2 receptors with cyproheptadine (2-5 mg/kg, i.v.) or ketanserin (2-5 mg/kg, i.v.) produced both hypotension and bradycardia, while stimulation of 5-HT2 receptors with 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10-250 mg/kg, i.v.) produced both hypertension and tachycardia. The dl-THP-induced hypotension and bradycardia could be reversed by DOI treatment. The data indicate that dl-THP decreases both arterial pressure and heart rate through a serotonergic release process in the hypothalamus.View full abstractDownload PDF (273K)
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