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Biomedical subjects

I Yamaguchi

Publications and source records attributed to I Yamaguchi.

At least 181 records · Page 10Linked to original sources
PubMed1993

Altered expression of ETB-receptor mRNA in the lung of rats with pulmonary hypertension.

To investigate the pathophysiologic role(s) of endothelin-1 (ET-1) in pulmonary hypertension, we studied the expression of ETB-receptor mRNA in the lung and venous plasma concentrations of ET-1 in rats with monocrotaline-induced pulmonary hypertension (PH). Three weeks after s.c. injection of monocrotaline (60 mg/kg), rats (PH rats, n = 6) were sacrificed. Vehicle-injected rats (n = 6) served as controls. The right ventricular systolic pressure of PH rats [58.0 +/- 4.7 mm Hg (mean +/- SEM)] was significantly higher than that in the vehicle-treated control rats (29.2 +/- 2.1; p < 0.01). Northern blot analysis showed that the expression of ETB-receptor mRNA decreased in the lung of PH rats. The venous plasma concentration of ET-1 measured by a sandwich-enzyme immunoassay was significantly higher in PH rats than in control rats (5.1 +/- 0.7 versus 1.3 +/- 0.2 pg/ml; p < 0.01). The present findings suggest that the expression of ETB-receptor mRNA decreases in the lung of PH rats, which might be closely related to the increase in plasma ET-1 concentration in these rats.

Animals↗
PubMed1993

Unusual electrocardiographic findings associated with type A Wolff-Parkinson-White syndrome.

A 50-year-old woman with Wolff-Parkinson-White (WPW) syndrome presented with unusual electrocardiographic (ECG) findings following the termination of paroxysmal supraventricular tachycardia. The ECG showed three different QRS complexes and irregular R-R intervals. These QRS complexes consisted of: (1) narrow QRS; (2) wide QRS with delta wave; and (3) wide QRS with left bundle branch block (LBBB). The mechanisms of these findings, revealed by electrophysiological study, were: (1) intermittent anterograde left-sided accessory pathway conduction; (2) rate-dependent ipsilateral LBBB; and (3) intermittent retrogradely conducted atrial echoes that occurred due to intraventricular conduction delay resulting from LBBB. Cases of WPW syndrome with these unusual ECG findings, which were clearly interpreted by electrophysiological study, are rare.

Bundle-Branch Block↗
PubMed1993

Expression of dopamine D1A receptor gene in proximal tubule of rat kidneys.

The existence of dopamine receptor subtypes outside the central nervous system has been suggested by pharmacological and biochemical techniques. Whether the renal dopamine receptors are distinct from those cloned from the brain remains to be determined. Indeed, the expression of any of these receptor genes in the kidney has not been demonstrated definitively. In this study, we amplified D1A receptor cDNA from microdissected proximal convoluted tubules of the rat kidney by reverse transcription-polymerase chain reaction; primers were based on the sequence of rat D1A cDNA cloned from the brain and corresponded to the third cytoplasmic loop of the receptor. Specificity of the amplified products was verified by restriction analysis, Southern blots, and sequencing. Furthermore, solution hybridization indicated the presence of a single ribonuclease-protected RNA species corresponding to the D1A receptor mRNA in proximal tubules. These studies report for the first time the presence of D1A receptor message in the kidney.

Animals↗
PubMed1993

Renal dopamine-1 receptors in hypertensive inbred rat strains with and without hyperactivity.

Renal dopamine-1 (DA-1) receptors are involved in the regulation of sodium transport in several nephron segments, including the proximal convoluted tubule (PCT). DA-1 receptors in the PCT and cortical collecting duct of normotensive rats are linked to the stimulation of adenylyl cyclase (AC). We have reported a defect in the DA-1 receptor/AC coupling in the PCT of the spontaneously hypertensive rat (SHR) of the Okamoto-Aoki strain. Hyperactivity and hypertension are both expressed in the SHR. To determine if the DA-1 receptor coupling defect is associated with hyperactivity or hypertension, we studied the DA-1 receptor in the PCT of two new inbred rat strains derived from the SHR: the hyperactive WKHA and the hypertensive WKHT rat. Tail-cuff blood pressures taken at 4 weeks indicated that WKHT rats were not hypertensive (86 +/- 3 mm Hg, n = 6), whereas at 12 weeks systolic pressures in both SHR and WKHT rats exceeded 150 mm Hg. Hyperactivity, however, was noted in WKHA rats even at this early age. Basal AC activity was similar in WKHA and WKHT PCT in either age group. In the older rats, the DA-1 agonist fenoldopam (10(-7) mol/L) stimulated AC activity in WKHA (70.6 +/- 16.1 fmol per 3 mm PCT per 20 minutes, n = 3) but not in WKHT PCT (43.3 +/- 5.3 fmol per 3 mm PCT per 20 minutes, n = 4). Gpp(NH)p (10(-5) mol/L), a nonhydrolyzable GTP analogue, stimulated AC activity to a similar extent in WKHA and WKHT PCT.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Contribution of endogenous endothelin-1 to the progression of cardiopulmonary alterations in rats with monocrotaline-induced pulmonary hypertension.

Endothelin-1 (ET-1) is known to have potent contractile and proliferative effects on vascular smooth muscle cells and is known to induce myocardial cell hypertrophy. We studied the pathophysiological role of endogenous ET-1 in rats with monocrotaline-induced pulmonary hypertension. Four-week-old rats were given a single subcutaneous injection of 60 mg/kg monocrotaline (MCT rats) or saline (control rats) and were killed after 6, 10, 14, 18, and 25 days. In the MCT rats, right ventricular systolic pressure progressively increased and right ventricular hypertrophy developed in a parallel fashion. The venous plasma ET-1 concentration also progressively increased, and this increase preceded the development of pulmonary hypertension. The isolated pulmonary artery exhibited a significantly weaker response to ET-1 in the MCT rats on day 25 but not on days 6 and 14. In the MCT rats, the expression of prepro ET-1 mRNA as measured by Northern blot analysis significantly increased in the heart on days 18 and 25, whereas it gradually decreased in the lungs. The peptide level of ET-1 in the lungs also significantly decreased in the pulmonary hypertensive stage. The expression of prepro ET-1 mRNA had increased by day 6 only in the kidneys. Continuous infusion of BQ-123, a selective ETA receptor antagonist, by an osmotic minipump (14.3 mg per day per rat for 18 days) significantly inhibited the progression of both pulmonary hypertension (right ventricular systolic pressure, 77.8 +/- 4.2 [mean +/- SEM] mm Hg [n = 10] versus 52.3 +/- 2.4 mm Hg [n = 7]; P < .01) and right ventricular hypertrophy (right ventricle/[left ventricle +/- septum], 0.56 +/- 0.03 [n = 10] versus 0.41 +/- 0.02 [n = 7]; P < .01). Histological examination revealed that BQ-123 also effectively prevented pulmonary arterial medial thickening. The inhibition of right ventricular hypertrophy by BQ-123 may be partly ascribed to the blockade of excessive stimulation of the heart by ET-1, in addition to the prevention of pulmonary hypertension. The present findings suggest that endogenous ET-1 contributes to the progression of cardiopulmonary alterations in rats with MCT-induced pulmonary hypertension.

Animals↗
PubMed1993

Changes in creatine kinase M localization in acute ischemic myocardial cells. Immunoelectron microscopic studies.

To clarify the changes in creatine kinase M localization along with the progress of myocardial ischemia, immunoelectron microscopic studies were performed using rabbit anti-canine creatine kinase M Fab'-horseradish peroxidase conjugate in 21 dogs. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery for 15 (n = 5), 30 (n = 5), 60 (n = 5), or 180 (n = 4) minutes. Two dogs were used as normal controls. As we have already demonstrated, most creatine kinase M in normal myocardial cells was localized over the entire A band in association with the thick filament, suggesting that creatine kinase in this region (A-band creatine kinase) was the enzyme coupled with myosin ATPase. After 15 minutes of ischemia, creatine kinase M showed only minimal changes in its location, indicating that A-band creatine kinase still has the ability to couple with myosin ATPase (reversible injury). However, after 30 minutes of ischemia, A-band creatine kinase diffused markedly to the I band (transitional phase), and after 60 minutes of ischemia, it leaked out to extracellular spaces (irreversible injury). After 180 minutes of ischemia, most A-band creatine kinase disappeared from the myocardial cells (coagulation necrosis). These features of creatine kinase M localization seemed to reflect each stage of ischemic cell injury. We conclude that myocardial ischemia results in a dissociation of creatine kinase molecules from the thick filament, which leads the energy transport system to destruction.

Acute Disease↗
PubMed1993

Characterization of heparin-induced osteopenia in rats.

Heparin has been known to induce osteopenia, but its precise mechanism of action is unknown. In the present study, we examined the effect of heparin on the rat femur using single photon absorptiometry and characterized the osteopenia biochemically and pharmacologically. Daily heparin injection dose dependently induced osteopenia in rats. Significant bone loss was observed from 2 weeks after starting heparin treatment (2000 U/kg.day) and peaked at 4 weeks. Serum PTH levels were significantly elevated from 1 week onward after starting heparin treatment, whereas no significant changes were seen in serum total calcium or ionized calcium levels. A bone resorption inhibitor, FR78844 (a bisphosphonate compound), significantly attenuated the heparin-induced osteopenia, as did 1 alpha-hydroxyvitamin D3; with the latter, the effective dose was 10 times lower than that needed for a similar effect against immobilization and ovariectomy-induced osteopenia, suggesting an up-regulation of 1 alpha, 25-dihydroxyvitamin D3 receptors in the heparin-treated rats. This speculation was supported by the finding that serum 1 alpha, 25-dihydroxyvitamin D levels were significantly decreased by 54% in the heparin-treated rats compared to those in normal rats. These results suggest that the enhanced bone resorption by high PTH blood levels and the reduction of 1 alpha, 25-dihydroxyvitamin D are involved in the pathogenesis of heparin-induced osteopenia.

Absorptiometry, Photon↗
PubMed1993

Age-related changes of sinus node function and autonomic regulation in subjects without sinus node disease--assessment by pharmacologic autonomic blockade.

To assess the relationship between aging and autonomic regulation of sinus node function, 56 subjects of various ages (range 14-75 years, mean 43 +/- 19 years) without sinus node disease were studied. Heart rate, corrected sinus node recovery time and sinoatrial conduction time were measured before (basic) and after (intrinsic) pharmacologic autonomic blockade (propranolol + atropine i.v.). Percent chronotropies of the above parameters were calculated by a modified Jordan's method. Basic heart rate and basic corrected sinus node recovery time did not vary with age (r = -0.15, r = 0.08, respectively), while basic sinoatrial conduction time tended to increase with age (r = 0.32, p < 0.05). Intrinsic heart rate decreased (r = -0.76, p < 0.001), and intrinsic corrected sinus node recovery time and intrinsic sinoatrial conduction time both increased with age (r = 0.55, p < 0.001; r = 0.56, p < 0.001, respectively). The younger the subject, the more negative the percent chronotropies of the above parameters were, and the percent chronotropies correlated positively with age (r = 0.68, p < 0.001; r = 0.52, p < 0.001 and r = 0.34, p < 0.05, respectively). In conclusion, intrinsic sinus node functions deteriorated with age. Furthermore, parasympathetic tone on the sinus node functions decreased with age, which may compensate for age-related deterioration of intrinsic sinus node function.

Adolescent↗
PubMed1993

Response of post-ischemic myocardium to sympathetic stimulation--relation to local norepinephrine release.

Myocardial ischemia interrupts neurotransmission and causes the depression of norepinephrine release. However, the effects of sympathetic nerve stimulation on neurotransmission and norepinephrine release in post-ischemic myocardium are not well defined. We measured regional myocardial length and norepinephrine (NE) release during sympathetic nerve stimulation in anesthetized dogs. Dogs were divided into 2 groups: Group 1 (n = 14); sympathetic nerve stimulation, Group 2 (n = 9); pre-treatment with alpha-blockade yohimbine hydrochloride (0.2 mg/kg) followed by sympathetic nerve stimulation. The left anterior descending artery was occluded for 15 min. Sympathetic nerve stimulation was performed before coronary occlusion and after reperfusion. In group 1, the decrease in systolic shortening in the ischemic region persisted for more than 60 min. Although sympathetic nerve stimulation caused an increase in systolic shortening, it was lower than the pre-ischemic value. NE release from the post-ischemic myocardium remained decreased for 60 min. The decrease in the post-ischemic myocardial response to sympathetic nerve stimulation was associated with diminished NE release. When the cardiac sympathetic nerve was denervated with an epicardial phenol application, NE release decreased even further. In group 2, NE release did not decrease following reperfusion. These results suggest that sympathetic nerve conduction is not completely impaired in post-ischemic myocardium and that pre-synaptic alpha -2 receptors might play an important role in diminished NE release.

Animals↗
PubMed1993

Evidence for beta-adrenoceptors in rat proximal convoluted tubules.

It is well documented that renal catecholamines, acting as paracrine or autocrine substances, modulate reabsorption of sodium and other substances in renal tubules. However, beta-receptors or the resulting stimulation of adenylate cyclase (AC) have not been measured directly in the proximal convoluted tubules (PCT) of mammalian kidney. In this study, the beta adrenergic receptors in the PCT from rat kidney were characterized pharmacologically by measuring agonist stimulated adenylate cyclase activity. Isoproterenol (ISO) (10 microM) significantly increased AC activity in the microdissected PCT (ISO, 193.0 +/- 23.6 vs basal, 118.7 +/- 14.3 fmol/mm/20; n = 8, p = 0.004). The stimulation of AC in PCT by ISO was blocked by 10 microM propranolol (p < 0.01); it was also blocked by either the beta-1-adrenergic blocker, 10 microM atenolol (p < 0.05), or the beta-2-adrenergic blocker, 10 microM ICI-118551 (p < 0.05). The beta adrenergic receptor binding sites were localized by autoradiography; specific [125I] iodocyanopindolol ([125I] ICYP) binding could be measured in the microdissected rat PCT. In conclusion, these findings provide evidence for beta adrenergic receptors in the PCT in rat kidney by radioligand binding and beta adrenergic agonist stimulated AC activity.

Adenylyl Cyclases↗
PubMed1993

[Borderline hypertension].

According to WHO criteria in 1978, borderline hypertension is defined as systolic blood pressure between 140 and 159 mmHg and/or diastolic blood pressure between 90 and 94 mmHg. Compared with direct intravascular pressure measurement, values obtained by the conventional cuff method were 2 mmHg lower in systolic pressure and 2 mmHg higher in diastolic pressure. The precision of the cuff method was approximately +/- 4 mmHg in both systolic and diastolic pressures. In 20 patients with mild hypertension, arterial pressure fluctuated with respiration within ranges from 6 to 32 mmHg in systole and from 3 to 14 mmHg in diastole. From these results, repetitive blood pressure measurements are recommended for the diagnosis of borderline hypertension. Borderline hypertension is the most sensitive predictor of definite hypertension in the future. Long term follow up should be stressed.

Age Factors↗
PubMed1992

Effect of nilvadipine on balloon catheterization-induced intimal thickening of the coronary artery in miniature pigs.

The effect of nilvadipine on balloon catheterization-induced intimal thickening of the coronary artery was examined in miniature pigs. A diffuse intimal thickening was observed in vehicle-treated controls 6 weeks after balloon catheterization. The histologic features of the intimal thickening resembled those of early atherosclerotic lesions and restenosis after percutaneous transluminal coronary angioplasty (PTCA). Nilvadipine given in a daily dose of 10 mg/kg (subcutaneously, s.c.) for 6 weeks significantly inhibited intimal thickening. The ratio of the cross-sectional area of the intima to the cross-sectional area of the media was significantly reduced by 62% in nilvadipine-treated animals. These results suggest that nilvadipine may prevent or exert beneficial effects on coronary arterial injuries such as atherosclerosis and restenosis after PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1992

Effects of the new angiotensin-converting enzyme inhibitor imidapril on renal hemodynamics and function in anesthetized dogs.

The effects of a new angiotensin-converting enzyme (ACE) inhibitor, imidapril hydrochloride ((-)-(4S)-3-[(2S)-2- [[(1S)-1-ethoxycarbonyl-3-phenylpropyl]amino]propionyl]- 1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) and of its active metabolite, 6366 A (CAS 89371-44-8) on renal function were studied in anesthetized dogs and compared to the effects of enalapril and its active metabolite, enalaprilat. Intravenous (i.v.) administration of 6366 A at 30 micrograms/kg strongly inhibited angiotensin I-induced renal vasoconstrictive and pressor responses. 6366 A promptly lowered blood pressure and renal vascular resistance, and caused clear increases in renal blood flow and glomerular filtration rate. It also increased urine volume and urinary excretion of sodium and chloride. These renal effects were also produced by intraduodenal (i.d.) administration of 2 mg/kg of imidapril. However, the effects of i.d. imidapril began later, developed gradually and reached a plateau after 2 to 3 h. Enalaprilat (30 micrograms/kg i.v.) and enalapril (2 mg/kg i.d.) had renal effects similar to 6366 A and imidapril. In conclusion, the ACE inhibitor imidapril has beneficial effects on renal function via its active metabolite, and the effects appear to be essentially identical to those of enalapril.

Anesthesia↗