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Biomedical subjects

H Ijichi

Publications and source records attributed to H Ijichi.

At least 55 records · Page 3Linked to original sources

Dopaminergic modulation of salt sensitivity in patients with essential hypertension.

The present study was designed to investigate the possible role of dopaminergic mechanisms in contributing to the pathogenesis of hypertension in salt sensitive patients. Eighteen patients with essential hypertension were studied while under a diet ranging from low salt to high salt, which enabled a classification in "salt-sensitive" (SS) and "nonsalt-sensitive" (NSS) groups based on a tentative criteria of a 10% increase of mean blood pressure with high salt diet. The SS patients showed reduced urinary excretion of sodium as compared with that from NSS patients. Urinary norepinephrine excretion in all patients with salt loading was suppressed, but urinary excretion of epinephrine showed a tendency to increase in SS patients after salt loading. Urinary excretion of dopamine increased in NSS patients with salt loading, but did not change in SS patients. To further evaluate the role of dopaminergic mechanisms in salt-sensitive hypertension, metoclopramide, a dopamine antagonist, was injected intravenously to all patients. With salt loading, plasma aldosterone levels increased after injection of metoclopramide in NSS patients, but did not change in SS patients. These results suggest that salt-sensitive hypertension is modulated by dopaminergic activity, which in turn is attenuated in SS patients. Decreased dopaminergic activity induced sodium retention both by a direct effect on the kidney as well as indirectly via relatively increased aldosterone secretion. Both mechanisms would help to increase intravascular volume and blood pressure in salt-sensitive hypertension.

Aged↗

Inversion of chromosome 3 in a case of chronic myelogenous leukemia with abnormal thrombopoiesis.

A patient with chronic myelogenous leukemia (CML) associated with a remarkable increase of micromegakaryocytes in bone marrow was revealed to have an abnormality of a long arm of chromosome #3, i.e., inv(3)(q21q26), in addition to a complex Ph translocation: t(9;22;15)(q34;q11;q22). Although several cases of acute leukemia with inv(3)(q21q26) and abnormal megakaryocytes have been reported, this is the first case in which the association of inv(3)(q21q26) with a megakaryocytic abnormality was observed in a patient with CML. Our findings suggest that this structural rearrangement may be more specifically associated with abnormal thrombopoiesis than are other structural anomalies of 3q.

Blood Platelets↗

Centrally induced cardiovascular and sympathetic responses to adrenocorticotrophic hormone.

To investigate the effects of adrenocorticotrophic hormone on central cardiovascular regulation, an intracerebroventricular injection of the drug was given to male Wistar rats. With doses of 1 microgram and 10 micrograms per rat, blood pressure began to rise within 1 min, attaining a maximum value 5-10 min later. Both heart rate and abdominal sympathetic nerve activity increased simultaneously with the rise in blood pressure. Injection into the fourth ventricle or intravenous administration of the drug elicited no appreciable cardiovascular responses. These results suggest that endogenous adrenocorticotrophic hormone produced locally in the hypothalamus may participate in central cardiovascular regulation by increasing sympathetic outflow.

Action Potentials↗

Cardiovascular and sympathetic responses to ouabain injected into the hypothalamus in rats.

To investigate the effects of sodium-potassium activated adenosine triphosphatase inhibition on central cardiovascular regulation a microinjection of ouabain was given into the hypothalamus of urethane anaesthetised rats. Doses of 0.01-1.0 micrograms per rat injected into the posterior hypothalamus produced a rise in blood pressure within 1 min, the maximum rise occurring 15-20 min later in a dose dependent manner. Both heart rate and abdominal sympathetic nerve activity increased with the rise in blood pressure. Ouabain injected into either the anterior preoptic hypothalamus or the ventromedial hypothalamus produced no notable cardiovascular responses. These results suggest that an endogenous digitalis like substance produced in the hypothalamus as a result of sodium loading may participate in central cardiovascular regulation by increasing sympathetic outflow in the discrete area of the brain, as does ouabain.

Action Potentials↗

Regional differences of myocyte hypertrophy and three-dimensional deformation of the heart.

Cross-sectional area was compared between the latitudinally and longitudinally oriented muscle fibers of the hypertrophied left ventricle of the rat heart under aortic banding and isoproterenol infusion. In addition, end-diastolic three-dimensional deformation of the left ventricle as expressed by cavity volume and eccentricity was examined in the early and chronic stages of these treatments. Under aortic banding, myocyte hypertrophy occurred to a greater extent in the latitudinally oriented fibers of the midwall layer than in the longitudinal fibers of the inner and outer layers. Such a regional difference of hypertrophy was not seen under isoproterenol infusion. At the early stage of aortic banding, the left ventricle at end diastole was more dilated and spherical, whereas at the acute stage of isoproterenol infusion, it was more decreased in size and prolate than that of the controls. The deformation of the left ventricle at the early stage of aortic banding is considered to cause, during diastole, axial stretching and increase in tensile stress more on the latitudinal fibers, leading them to the predominant hypertrophy.

Animals↗

Attenuated development of hypertension by chronic administration of bromocriptine in Doca-salt hypertensive rats.

The aim of the study was to investigate whether or not the development of hypertension is influenced by chronic treatment with bromocriptine and/or domperidone. Rats treated with DOCA-salt were divided into 4 groups: control with vehicle, bromocriptine, bromocriptine with domperidone, and domperidone. Increased blood pressure by DOCA-salt treatment was significantly suppressed by treatment with bromocriptine and this bromocriptine suppression was significantly blocked by treatment with domperidone. Increased urinary excretion of norepinephrine by DOCA-salt treatment was significantly suppressed by bromocriptine and the inhibiting effect of bromocriptine disappeared with domperidone. In the four groups of rats, there were significant correlations between systolic blood pressure and urinary excretion of norepinephrine, systolic blood pressure and urinary excretion of epinephrine, and urinary excretion of dopamine and sodium. These results suggest that the chronic effect of bromocriptine is to suppress development of DOCA-salt hypertension, mainly through peripheral mechanisms which are involved in the decreased release of norepinephrine.

Animals↗

Hypotension and hypothalamic depression produced by intracerebroventricular injections of GABA in spontaneously hypertensive rats.

To determine the central effects of 4-Amino-n-butyric acid (GABA), pressor and sympathetic nerve responses to electrical stimulation of the ventromedial hypothalamus were recorded following the intracerebroventricular (ICV) injection of GABA. In normotensive Wistar rats, anesthetized with urethane, ICV injections of GABA (50-200 micrograms) reduced sympathetic nerve activity, arterial blood pressure, and heart rate in a dose-dependent manner. Graded electrical stimulation of the ventromedial hypothalamus (50, 100, 150 microA) increased not only mean blood pressure but also the rate of sympathetic nerve firing, and both responses were attenuated by GABA pretreatment (100, 200 micrograms, ICV). In spontaneously hypertensive rats (SHR), ICV-injected GABA also reduced sympathetic and cardiovascular activity, but the magnitude of depressor responses was significantly larger in SHR than in normotensive Wister Kyoto controls (WKY). Pressor and sympathetic nerve responses elicited by ventromedial hypothalamic stimulation were initially larger in SHR than in WKY, but upon subsequent ICV injection of GABA, hypothalamic responsiveness in SHR was inhibited more prominently and became comparable to that in WKY. These results suggest that by depressing hypothalamic function, centrally injected GABA decreases sympathetic nerve activity to thereby lower blood pressure and heart rate, and in SHR, ICV-injected GABA reversed hypothalamo-sympathetic hyperactivity and thus attenuated hypertension.

Animals↗

Hypotensive responses to centrally administered taurine in DOCA-salt hypertensive and spontaneously hypertensive rats.

The present study was designed to investigate the short-term effects of intracerebroventricularly-administered taurine in DOCA-salt hypertensive (DOCA), spontaneously hypertensive (SHR) and their respective normotensive control rats anesthetized with urethane. Blood pressure, heart rate and sympathetic nerve activity were consistently decreased following the injection of taurine 150 micrograms per rat in hypertensive rats as well as in normotensive controls of the two groups. Percent changes from the baselines in blood pressure, heart rate and sympathetic nerve activity were significantly larger in DOCA-salt hypertensive rats than those in sham operated rats. In contrast, percent changes in blood pressure and sympathetic nerve activity were not significantly different between spontaneously hypertensive rats and normotensive wistar kyoto rats. These result show that the responses of blood pressure, heart rate and sympathetic nerve activity to intracerebroventricular taurine are different between spontaneously hypertensive rats and DOCA-salt hypertensive rats. It appears that augmented vasodepressor responses to taurine in DOCA-salt hypertensive rats, as compared to spontaneously hypertensive rats, are due to enhanced inhibition of the sympathetic outflow.

Animals↗

Prostacyclin generation by cultured human vascular endothelial cells with reference to angiotensin I-converting enzyme.

Prostacyclin (PGI2) generation has been known to be regulated by several endogenous vasoactive substances, and in this study the relationship between angiotensin I-converting enzyme (ACE) related substances and PGI2 generation was investigated using cultured human vascular endothelial cells. Addition of angiotensin I (AI) or bradykinin (BK) enhanced PGI2 generation and increased the level of ACE activity in the culture medium, while the addition of ACE inhibitor (captopril) caused a dose dependent suppression of PGI2 generation and ACE activity. The enhancement of PGI2 generation induced by AI or BK was not affected by pretreatment with captopril, and angiotensin II (AII) did not show any effect on either PGI2 generation or ACE activity. Through these experimental results, the conversion of AI to AII by ACE was considered not to cause the enhancement of PGI2 generation. Captopril solely inhibited PGI2 generation and the reported hypothesis that captopril enhances PGI2 generation by the accumulation of AI or BK via inhibition of ACE was not confirmed in this experimental system. Rather, it is proposed that AI or BK induced PGI2 generation may be regulated by the increased breakdown of AI or BK, as an autoregulation mechanism, that is derived from increased ACE activity by AI or BK.

Angiotensin I↗

Enhanced renal sympathetic nerve activity in response to salt loading in rats.

To analyze the conflicting data on the relationship between sodium intake and sympathetic activity, the effects of a chronically excessive intake of sodium on renal sympathetic activity and blood pressure were investigated in normotensive rats. Renal sympathetic activity was estimated by urinary excretion of free norepinephrine (NE) and the turnover of NE in the kidneys. Blood pressure increased in rats receiving a high sodium diet when compared with that of the basal sodium diet. Urinary-free NE, epinephrine (E) and dopamine (DA) excretions in rats receiving a high sodium diet were enhanced significantly from those in the basal sodium diet. The turnover of NE in the kidneys was more enhanced in the high sodium group than in the basal sodium group. By blocking the sympathetic tone with ganglionic blockade, hexamethonium, enhanced excretion of urinary NE and elevation of blood pressure in response to salt loading were blocked to the levels of the basal sodium diet. These results suggest that a chronically excessive intake of sodium enhances the renal sympathetic and adreno-medullary activities, leading to a rise in blood pressure in normotensive rats.

Animals↗

The significance of duration of salt loading on cardiovascular response and urinary excretion of catecholamine in rats.

To analyze the conflicting data on the relationship between sodium intake and catecholamine release, the effect of the duration of high sodium loading on cardiovascular response and catecholamine release was examined in conscious rats. Urinary excretions of norepinephrine (NE), and dopamine (DA) were measured frequently over a 4 week period. Male Wistar rats at 4 weeks of age were given a diet containing either basal (0.3%) or high (3.1%) sodium content. Systolic blood pressure was measured weekly by the tail cuff method. Twenty-four hour urine collections were made for analysis of catecholamines in metabolic cages every other day during the initial 2 weeks and once a week in the following 2 weeks of salt loading. High sodium intake resulted in a rise in blood pressure and a reduction in heart rate. Bradycardia was significant during the initial 2 weeks and not significant during the following 2 weeks after the initiation of salt loading. Urinary excretion of NE did not change during the initial 2 weeks of salt loading but increased significantly following the 2 week period after salt loading. Urinary excretion of DA increased diphasically, showing the first peak at 1 week after salt loading and the second peak at 4 weeks after the initiation of salt loading. These results suggest that the heart rate and urinary excretion of catecholamine are influenced by the duration of salt loading. When we estimate the effect of salt loading on cardiovascular response and urinary excretion of catecholamine, we should draw attention to the importance of the duration of salt loading, because this duration of time further elicites delayed response in the sympathetic nervous system.

Animals↗

Inhibition of TSH binding to chicken thyroid by some cases of LATS (long acting thyroid stimulator).

TSH receptor antibody (TRAb) activity using chicken thyroid receptor (c-TRAb) and porcine thyroid receptor (p-TRAb) was determined by the incubation of 125I-bovine TSH with each receptor. Both c-TRAb and p-TRAb activity in LATS positive and negative Graves' sera were compared. 15 out of 39 LATS positive sera and 4 out of 46 LATS negative sera had positive c-TRAb activity. On the other hand, all LATS positive sera and 33 out of 46 LATS negative sera had positive p-TRAb activity. No relationship between c-TRAb and p-TRAb activity was observed, and there was also no correlation between c-TRAb and LATS activity. Changes in c-TRAb, p-TRAb and LATS activity in the clinical course of patients with Graves' disease were examined. These activities were parallel in some cases, but in others they were not. A weak c-TRAb activity was observed in 4 out of 29 Hashimoto's disease, but all cases with thyroid cancer and subacute thyroiditis showed no activity. Sera with positive c-TRAb activity did not stimulate chicken thyroid in chick bioassay. These results suggest that some cases of TRAb in Graves' disease (mainly LATS) inhibit TSH binding to chicken thyroid receptor (non-mammalian species) in the same way as mammalian thyroid, but may not have any stimulatory action on thyroid hormone synthesis. It is interesting to note that TRAb including LATS have the similar effect on TSH receptor even in nonmammalian species.

Animals↗

Augmented vasodepressor and sympathetic responses to intracerebroventricular injections of diltiazem, a calcium channel blocker, in DOCA-salt hypertensive rats.

The role of the calcium ion in central cardiovascular regulation was investigated by injecting a calcium channel blocker, diltiazem, intracerebroventricularly (i.c.v.) in urethane-anaesthetized, DOCA-salt hypertensive rats. This produced a fall in blood pressure and bradycardia with corresponding decreases in abdominal sympathetic nerve activity. However, a similar amount of diltiazem injected intravenously (i.v.) did not affect abdominal sympathetic nerve activity despite an accompanying vasodepression. The responses to i.v. injections of diltiazem were not different between the two groups; however, the magnitude of the blood pressure fall, bradycardia and sympathetic inhibition with i.c.v. injections was greater in the DOCA rats than in the sham-operated animals. These results suggest that diltiazem causes the central nervous system to decrease the sympathetic nerve outflow. The augmented central vasodepressor responses to diltiazem in DOCA-salt hypertensive rats may indicate that calcium metabolism in the central nervous system is disrupted and that this is of importance in the pathogenesis of DOCA-salt hypertension in rats.

Animals↗

Evidence for a digitalis-like substance in the hypothalamo-pituitary axis in rats.

The origin of an endogenous digitalis-like substance in rats was investigated. The tissue content of the substance measured by radio-immunoassay was highest in the pituitary gland, with a decreasing gradient through the hypothalamus, forebrain, cerebellum, brain stem, heart, liver and kidney. Sodium loading decreased the content in the hypothalamus and increased the urinary excretion of the substance. The urinary output of the substance decreased after electrical lesions of the anteroventral third ventricle in the brain. The content increased in the hypothalamus and decreased in the plasma when the axonal flow of neurosecretion was interrupted with intracerebroventricular injections of colchicine. These results suggest that the digitalis-like substance could be produced in the hypothalamus and secreted from the pituitary gland like vasopressin, and that sodium loading increases the turnover of the substance in the hypothalamus.

Animals↗

[Left ventricular function during atrial fibrillation assessed by left ventricular function curve using ECG-gated blood pool scintigraphy].

Cardiac function is difficult to assess in patients with atrial fibrillation due to the widely fluctuating cycle lengths resulting in variable ventricular hemodynamics. With respect to ECG-gated blood pool scintigraphy, distortion of the time activity curve occurs due to a summation of irregular cycle lengths. Therefore, performing such a study has been regarded meaningless. To evaluate left ventricular function during atrial fibrillation using scintigraphic technique, a new processing algorithm was devised to make multiple gated images which are discriminated by the preceding R-R interval, and left ventricular filling and function curves were established. The left ventricular filling curve, obtained by plotting end-diastolic volume against the preceding R-R intervals demonstrated an impairment of blood filling in cases of mitral stenosis and constrictive pericarditis, which resolved after mitral commissurotomy in case of mitral stenosis. The left ventricular function curve, established by plotting stroke volume against end-diastolic volume, was analyzed according to indices such as "slope" and "position". Both of these indices were significantly reduced in relation to the severity of heart failure according to the NYHA's functional classification and cardiomegaly on chest radiography. On individual comparisons of underlying diseases, the indices decreased in the following order; lone atrial fibrillation, hyperthyroidism, aging, hypertension, mitral valve disease, ischemic heart disease, dilated cardiomyopathy and aortic regurgitation. The indices correlated closely with ejection fraction. In cases of mitral regurgitation, however, the function curves were situated to the right and above those of lone atrial fibrillation and decreased in slope despite the fairly well-maintained ejection fraction. After treatment with digitalis and/or diuretics, the function curves shifted to the left and upward. In conclusion, left ventricular filling and function curves based on a newly-devised algorithm of ECG-gated blood pool scintigraphy are of considerable clinical value in evaluating cardiac performance in patients with atrial fibrillation. They are widely applicable to the assessment of therapeutic and interventional effects.

Atrial Fibrillation↗