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Biomedical subjects

T Ishimitsu

Publications and source records attributed to T Ishimitsu.

At least 109 records · Page 6Linked to original sources
PubMed1990

Relevance of vascular PGI2 synthase to vascular prostacyclin production in Dahl rats susceptible to salt-induced hypertension.

To assess the roles of prostacyclin (PGI2) synthase in vascular PGI2 generation, the enzymatic activity was examined in the mesenteric artery of Dahl S rats in the prehypertensive or hypertensive stage. Elevation of blood pressure in Dahl S rats was accompanied by an increase of vascular PGI2 synthase activity. The enzymatic activity was positively correlated to the blood pressure value. Similarly, impaired vascular capacity to generate PGI2, which was observed in prehypertensive Dahl S rats, was restored to the control level of Dahl R rats with the elevation of blood pressure. These data indicate that vascular PGI2 synthase activity is increased with blood pressure elevation, thereby contributing to the restoration of vascular capacity to generate PGI2 in Dahl S rats.

Animals↗
PubMed1990

Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell.

Indapamide, a nonthiazide diuretic, exhibits direct vasodilator action as well as natriuretic and diuretic effects. Although calcium antagonist-like activity has been addressed so far, the mechanisms for vasodilator effect are still uncertain. To understand the wide range of indapamide actions, we examined the effects of indapamide on the vascular eicosanoid generation and investigated its mechanisms by using rat vascular smooth muscle cells in culture. Indapamide uniquely increased the prostacyclin generation in the vascular smooth muscle cells in a dose-dependent manner, whereas it did not affect the vasoconstrictor thromboxane A2. Thiazide diuretics lowered the prostacyclin generation, while nonthiazide derivatives did not affect the biosynthesis. Enzymatic analysis revealed that indapamide affected neither [14C]arachidonate liberation nor prostacyclin synthase of the smooth muscle cells. Indapamide eliminated a stable free radical in a cell-free system, lowered the formation of malondialdehyde from lipid peroxides in rat brain homogenate, and reduced lipid peroxidation by the free radical generating system of xanthine-xanthine oxidase. Indeed, the scavenging action of indapamide significantly attenuated the inhibitory activity of 15-hydroperoxy-arachidonate to prostacyclin synthase activity. These results indicate that indapamide diuretic increases prostacyclin generation in the vascular smooth muscle cells possibly through antioxidant effects and that the enhanced prostacyclin generation is partly responsible for its direct vasodilator action.

Animals↗
PubMed1990

Roles of endogenous vasodepressor prostaglandins in growth of vascular smooth muscle cells in spontaneously hypertensive rats.

We designed experiments to investigate the roles of endogenous prostaglandins (PG) for the rapid proliferation of vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR). Both the basal and arachidonate-stimulated vasodepressor PG generations were significantly enhanced in the VSMC of SHR when they were at the 1st or 2nd passage. Conversely, the generating capacity was significantly lowered in the VSMC of SHR when the cells reached the 4th or older generation. Based on the (3H)thymidine uptake and doubling time of VSMC, the decline of PG generating capacity seen in the VSMC of SHR was markedly associated with the increased VSMC growth. Indeed, the stimulation of endogenous vasodepressor PG by arachidonate produced a decrease in (3H)thymidine uptake in the VSMC of Wistar-Kyoto rats, whereas the dose was not sufficient to retard the uptake in SHR. On the other hand, the PG synthesis inhibition by indomethacin, a cyclooxygenase inhibitor, significantly enhanced the uptake by the VSMC of SHR. Thus, these data indicate that the impaired vasodepressor PG system is at least partly responsible for the rapid VSMC growth in SHR.

Animals↗
PubMed1990

Nephrogenous cyclic GMP production during NaCl loading and ANP infusion.

To further study the mechanisms of the renal effects of ANP, we examined the effects of NaCl loading and ANP infusion on nephrogenous cGMP production. Six normotensives (NTs) and 7 essential hypertensives (HTs) were placed on 7-day low (3 g/day) and then 7-day high NaCl diets (20 g/day). On the last day of each period, the natriuretic and nephrogenous cGMP responses to ANP infusion at 25 ng/kg/min for 40 min were determined. ANP infusion markedly increased the plasma concentrations of ANP and cGMP and the urinary excretions of Na and cGMP. These changes were accompanied by a rise in nephrogenous cGMP. Increases in nephrogenous cGMP during ANP infusion were not different between HTs and NTs despite a greater natriuretic response in HTs. NaCl loading significantly increased the natriuretic response to ANP infusion in both groups. However, nephrogenous cGMP production induced by ANP infusion was not affected by changes in NaCl intake. Thus, although ANP-induced natriuresis is associated with an increase in nephrogenous cGMP, the natriuretic effect of ANP seems to be modified to a greater extent by indirect mechanisms such as renal perfusion pressure and body fluid volume status.

Adult↗
PubMed1990

[Mitral valve function after open mitral commissurotomy: assessment by Doppler echocardiography].

To evaluate mitral valve function and its long-term outcome after open mitral commissurotomy (OMC), we examined 39 patients using Doppler echocardiography. There were 13 males and 26 females; who were examined a total of 83 times after the surgery at about one year intervals (seven to 240 months, averaging 78 months). We measured the velocity of transmitral blood flow using the continuous wave Doppler method (CWD), and the transmitral pressure half time (PHT), mean velocity (m V) and peak velocity (pV) were calculated. The presence and severity of mitral regurgitation (MR) were assessed by color flow mapping. 1. PHT gradually increased and significantly correlated (r = 0.63, p less than 0.001) with the months passed after OMC. The regression line of PHT in postoperative months was "PHT = 0.70 x PMo + 83" (PMo = postoperative months). The mV and pV tended to increase gradually, but did not significantly correlate with the months passed after the surgery. 2. Among the 39 patients, 28 (72%) had MR, and their severity was classified as 1+ in two, 2+ in 19, 3+ in six and 4+ in one. Among 21 patients who had no MR before OMC, MR appeared in 12 (57%), and its severity was classified as 1+ in one, 2+ in nine and 3+ in two. All five patients with preoperative MR had MR postoperatively, and their severity was classified as 1+ in one, 2+ in two and 3+ in two. The presence of the preoperative MR of the remaining 13 patients was unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[A case of mitral valve prolapse associated with unusual posterior wall motion of the left ventricle: where has the myocardial theory gone?].

A case with mitral valve prolapse was reported in which unusual movement of the posterior left ventricular wall was observed. The patient was a 45-year-old woman. Physical examination revealed loud multiple clicks at the apex. An electrocardiogram revealed T wave inversion in leads 2, 3 and aVF. Two-dimensional and M-mode echocardiography disclosed mid-systolic buckling of the mitral valve and late systolic 'dip' in the posterior wall of the left ventricle. An exaggerated excursion of the posterior wall during early diastole was also recorded by M-mode echocardiography. Pulsed and M-mode color Doppler echocardiography detected unusual anterograde flow near the mitral valve. This flow coincided well in timing with the early diastolic exaggerated excursion of the posterior wall. A discussion was made on the relation between abnormal left ventricular wall motion and mitral valve prolapse.

Echocardiography, Doppler↗
PubMed1989

Effects of OKY-046, a selective thromboxane synthetase inhibitor, on blood pressure and thromboxane synthesis in spontaneously hypertensive rats.

The effects of OKY-046, a specific thromboxane (TX) synthetase inhibitor, on blood pressure, urinary TX excretion, TX synthesis in blood platelets, kidney slices and aortic strips, were evaluated in adult spontaneously hypertensive rats (SHR). OKY-046 was dissolved in drinking water at concentrations of 1, 10, 100 mg/dl. The average intakes of OKY-046 were 1.4 +/- 0.1, 13.0 +/- 1.1, and 147 +/- 12 mg/kg/day, in rats who took 1, 10, 100 mg/dl of OKY-046 solutions for drinking water, respectively. The systolic blood pressure was significantly decreased by 34 mmHg only with the high dose of OKY-046 (147 mg/kg/day). OKY-046 suppressed the platelet aggregability to ADP and the release of TX B2, a stable metabolite of TX A2, from blood platelets in a dose-dependent fashion. Urinary excretion of TX B2 decreased significantly in both groups treated with moderate (13.0 mg/kg/day) and high doses of OKY-046 (147 mg/kg/day). The release of TX B2 from kidney slices was decreased only by the high dose of OKY-046, while the release of TX B2 from aortic strips was not changed even by the high dose of OKY-046. OKY-046 had no effect on urinary excretion of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, or, on its release from the kidney slices and aortic strips. These results suggest that the effect of OKY-046 on TX synthesis has organ specificity and that the antihypertensive effect of this drug in SHR is related to reduced renal TX synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Alteration of vascular thromboxane in rats with subtotal renal ablation.

To assess the roles of vascular prostaglandins in the hypertension of chronic renal failure, the release of prostacyclin and thromboxane (TX) from aorta was evaluated in male Sprague-Dawley rats, the renal mass of which was reduced by removing one kidney and two-thirds of the contralateral kidney ("5/6 nephrectomy"). Five-sixths nephrectomy was followed by significant rises in serum creatinine to 0.55 +/- 0.03 mg/dl and urea nitrogen to 42.9 +/- 3.8 mg/dl, with a concomitant rise in mean blood pressure from 121.6 +/- 1.6 mmHg to 155.3 +/- 8.4 mmHg. In 5/6 nephrectomized rats, the release of TX A2 from aorta, as measured by its stable metabolite TX B2, increased by 60% (p less than 0.01) and prostacyclin, as measured by its stable metabolite 6-keto-prostaglandin, F1 alpha (6-keto-PG F1 alpha) increased by 51% (p less than 0.05). The amounts of both TX B2 and 6-keto-PG F1 alpha released from aorta were closely related to the height of mean blood pressure. These results suggest that the enhanced vasoconstrictor TX production in the vascular walls may be relevant to hypertension in rats with subtotal renal ablation. The adaptive increase in prostacyclin production in the vascular walls may compensate for the elevation of blood pressure due to chronic renal failure in this animal model.

Animals↗
PubMed1989

Effect of alpha-human atrial natriuretic peptide on proteinuria in patients with primary glomerular diseases.

1. The effects of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) on urinary protein excretion were examined in nine healthy subjects and 20 patients with primary glomerular diseases who had proteinuria of 1.0 g or more per day. Synthetic alpha-hANP was intravenously infused into supine subjects at a rate of 8.3 pmol min-1 kg-1 for 40 min. 2. Before alpha-hANP infusion, the plasma concentration of immunoreactive alpha-hANP was significantly higher in the patients with glomerulonephritis than in the normal subjects (44.3 +/- 8.7 vs 19.4 +/- 3.0 pmol/l, mean +/- SEM, P less than 0.01) and it showed a positive correlation with mean arterial pressure (rs = 0.84, P less than 0.001) and a negative correlation with creatinine clearance (rs = -0.50, P less than 0.01). 3. During infusion of alpha-hANP, although the urinary excretion of protein did not change significantly in the normal subjects, it increased from 0.6 +/- 0.2 to 3.0 +/- 0.8 mg min-1 m-2 (P less than 0.001) in the patients with glomerulonephritis. The urinary protein/creatinine ratio did not change significantly in the former (from 0.18 +/- 0.05 to 0.22 +/- 0.06; NS), whereas it rose from 3.25 +/- 0.94 to 7.62 +/- 1.31 (P less than 0.001) in the latter. 4. The urinary excretions of albumin and of alpha 1-, alpha 2-, beta- and gamma-globulins, which were electrophoretically analysed, all increased in eight nephrotic patients during or immediately after infusion of alpha-hANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Alterations of the cardiovascular and renal prostaglandins and thromboxanes system in prehypertensive spontaneously hypertensive rats.

To assess the participation of cardiovascular eicosanoids (prostaglandins and thromboxanes) system in the initiation of genetic hypertension, we examined eicosanoids metabolism in the heart, aortic wall and kidney in prehypertensive and hypertensive rat models for spontaneous hypertension (SHR). Vasoconstrictor thromboxane A2 (TXA2) generation in the aortic wall was significantly enhanced by 49% in the prehypertensive and by 18% in the hypertensive SHR when compared to the respective normotensive Wistar-Kyoto rats. Cardiac TXA2 content was significantly increased as well by 14% in the prehypertensive and by 30% in the hypertensive SHR. Moreover, vascular vasodepressor eicosanoids generation was decreased by 10% for PGI2 and by 29% for PGD2 in the prehypertensive SHR although the alterations were eliminated in the hypertensive SHR. In contrast to the cardiovascular eicosanoids system, there was no difference in renocortical TXA2 content in either young or adult SHR while vasodepressor prostaglandins contents were decreased by 29% for PGE2 and by 33% for PGD2 in SHR when they were in the prehypertensive stage. Thus, in the prehypertensive stage of SHR, the cardiovascular eicosanoids system exhibited enhanced vasoconstrictor TXA2 and decreased vasodepressor prostaglandins, thereby producing a vasoconstrictor state. These data indicate that the alterations in the cardiovascular eicosanoids system partially contribute to the initiation of hypertension in SHR.

Animals↗
PubMed1989

A possible physiological role of atrial natriuretic peptide in body fluid volume regulation.

To study whether or not atrial natriuretic peptide (ANP) is physiologically involved in body fluid volume regulation, we examined the relationship between plasma ANP level and renal function during NaCl loading and ANP infusion. In study I, six normotensives (NTs) and seven hypertensives (HTs) were placed on 7-day low (3 g/day) and then 7-day high NaCl diets (20 g/day). The plasma ANP level increased by 60% (p less than 0.01) on the high NaCl diet. Although the plasma ANP level was higher in HTs than in NTs, the changes in plasma ANP due to NaCl loading were similar between the two groups. Furthermore, increases in urinary Na excretion due to ANP infusion at 25 ng/kg/min were greater for the high NaCl diet than for the low NaCl diet (p less than 0.02). In study II, graded doses of ANP were infusion into 16 other HTs and Nts on an 8 g/day NaCl diet. ANP infusion at 2.5 ng/kg/min increased the plasma levels of ANP by 80% (p less than 0.001). Such increments were associated with an increase in urinary Na excretion by 25% (p less than 0.02) in both HTs and NTs. This rise in plasma ANP was comparable to that induced by high NaCl intake. Thus, a slight increase in plasma ANP induced by dietary Na loading seems to augment renal Na excretion, suggesting that ANP may play a physiological role in body fluid volume regulation.

Adult↗
PubMed1989

[Is this mitral valve prolapse? A case of mitral regurgitation with early systolic murmur due to early systolic prolapse of the posterior leaflet].

This paper reports the findings of phonocardiograms, echocardiogram and Doppler echocardiograms in a case of a 50-year-old man with early mitral valve prolapse with an early systolic murmur. A characteristic early systolic crescendo murmur was recorded at the apex. By amyl nitrite inhalation, the early systolic murmur was attenuated and a late systolic murmur was evoked. On the contrary, methoxamine injection increased the intensity of the early systolic murmur. Early systolic prolapse and early systolic buckling were recorded by two-dimensional and M-mode echocardiography. The phase of mitral regurgitation detected by M-mode color Dopper echocardiography coincided well in timing with the early systolic murmur and the early systolic buckling recorded on the M-mode echocardiogram. A discussion was made on the mechanism of the early systolic mitral regurgitation due to early mitral valve prolapse.

Amyl Nitrite↗
PubMed1989

[New trends in diagnostic examinations in clinical cardiology].

There are various kinds of diagnostic examinations in the field of clinical cardiology. In this field, information concerning cardiac structure, dimensions (hypertrophy and dilatation) and cardiac functions are inevitably important. Noninvasive methods are desirable. Except for radiological examinations, electrocardiography and ultrasonic echocardiography are 2 main examinations in cardiology. Holter monitoring is one of the recent topics in clinical electro-cardiology. It is useful for the detection of rest angina or variant angina. Recently "silent myocardial ischemia" has been studied by using this method. This method is also useful for the study of arrhythmia, which is a major cause of sudden death. Quantitative analysis of arrhythmia in the studies of antiarrhythmic drugs can also be done by Holter monitoring. Late potential is also a topic in electro-cardiology. Ultrasonic echocardiography can detect the changes of cardiac structure and function. Doppler echocardiography, developed recently, has made it possible to estimate intracardiac pressure (especially pulmonary arterial pressure) noninvasively. With esophageal echocardiography findings in left atrium, such as thrombus or myxoma in left atrium can be obtained. The most appropriate tool must be selected from the many kinds of diagnostic examinations for efficient clinical diagnosis and therapy.

Echocardiography↗
PubMed1989

[The effects of ketanserin on vascular eicosanoid system in spontaneously hypertensive rats and their implications].

We designed experiments to reveal the effects of a S2 serotonergic receptor antagonist, ketanserin, on the vascular eicosanoid system and the relevance to medial hyperplasia in spontaneously hypertensive rats (SHR). 2-week ketanserin treatment (5 mg/kg/day) significantly decreased systolic blood pressure by 7% when compared to untreated SHR. The blood pressure reduction was associated with a significant decrease in vascular thromboxane A2 (TXA2) generation and sustained prostacyclin (PGI2) production, thereby shifting PGI2/TXA2 ratio toward vasodilatation. In contrast, the trichlormethiazide treatment, which achieved blood pressure reduction to almost the same extent, significantly decreased PGI2/TXA2 ratio. Vasodilator eicosanoids, e. g. PGI2, PGE2 and PGD2, dose-dependently decreased (3H)-thymidine uptake by vascular smooth muscle cells in culture whereas vasoconstrictor TXA2 enhanced (3H) thymidine uptake in a dose dependent manner. Indeed 2 x 10(-5) M ketanserin significantly decreased (3H) thymidine uptake by vascular smooth muscle cells by 48% although the same dose of methysergide, nonspecific serotonin inhibitor, did not affect the uptake by vascular smooth muscle cells. These results clearly indicate that the blood pressure reduction in ketanserin treatment is uniquely associated with a decrease in vascular thromboxane generation, and that it is possibly beneficial to protect vascular wall against medial hyperplasia of vascular smooth muscle cells, an integral component of arterial sclerotic changes in hypertension.

Animals↗
PubMed1988

Regulatory effects of eicosanoids on thymidine uptake by vascular smooth muscle cells of rats.

To define the roles of eicosanoids in vascular smooth muscle cells (VSMC) growth, we examined the effects of exogenous eicosanoids on (3H)thymidine uptake by cultured VSMC of Wistar rats. Stable prostacyclin (PGI2) analog, OP-41483, significantly decreased the incorporation of (3H)thymidine into deoxyribonucleic acid (DNA) of VSMC in a dose dependent manner from 10(-8) to 10(-4) M. Prostaglandin E2 (PGE2) and PGD2 ranging from 10(-8) to 10(-4) M also dose-dependently decreased the (3H)thymidine uptake by VSMC. In contrast, stable thromboxane A2 analog, STA2, significantly increased the incorporation of (3H)thymidine into DNA in a dose dependent manner from 10(-8) to 10(-4) M. The dose response curve of STA2 was shifted toward a lowered response when 10(-5) M PGI2 analog, PGE2 or PGD2 was added in the culture medium. Thus, it is indicated that vasodepressor eicosanoids decrease the proliferation of VSMC, whereas vasoconstrictor TXA2 enhances the VSMC growth. Vascular smooth muscle cells possibly autoregulate the cell proliferation through the eicosanoids generation.

Actins↗