[Aldosteronism and the related diseases].
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Adolescent↗
Biomedical subjects
T Saruta
Publications and source records attributed to T Saruta.
Transmural pressure inhibits nitric oxide release from human endothelial cells.
We examined the effect of transmural pressure on histamine-stimulated nitric oxide release from cultured endothelial cells prepared from human umbilical cord veins. PO2 and pH were kept constant throughout the experiments. Various levels of transmural pressure and atmospheric pressure (40, 80, 120 and 160 mm Hg) were applied. Nitric oxide release was inhibited in a pressure-dependent manner. The inhibitory effects were reversible, and nitric oxide had no effect on the morphology of the cells. Our results suggest that transmural pressure-mediated inhibition of nitric oxide release contributes to pressure-induced vasoconstriction and reduced endothelium-dependent relaxation in patients with hypertension.
Atmospheric Pressure↗
Arachidonic acid metabolites and alpha 2-adrenoceptor-mediated glucagon secretion in rats.
Effects of phospholipase A2 inhibitor, cyclooxygenase inhibitor and lipoxygenase inhibitor on glucagon secretion induced by the alpha 2-adrenergic agonist clonidine were studied in the isolated perfused rat pancreas. The phospholipase A2 inhibitor mepacrine at 25 and 50 mumol/l significantly inhibited glucagon secretion induced by 0.1 mumol/l clonidine (P less than 0.01, respectively), whereas 5 mumol/l mepacrine did not affect clonidine-induced glucagon secretion. Also, both 100 mumol/l acetylsalicylic acid (cyclooxygenase inhibitor) and 100 mumol/l caffeic acid (lipoxygenase inhibitor) significantly inhibited clonidine-induced glucagon secretion (P less than 0.01, respectively), whereas neither 10 mumol/l acetylsalicylic acid nor 10 mumol/l caffeic acid affected clonidine-induced glucagon secretion. None of the drugs at the tested concentrations affected insulin secretion at a glucose concentration of 5.5 mmol/l. These results suggest that not only cyclooxygenase metabolites but also lipoxygenase metabolites are involved in the stimulation of glucagon secretion mediated through the alpha 2-adrenergic receptors in perfused rat pancreas.
Animals↗
Suppression of development of diabetes in NOD mice by lactate dehydrogenase virus infection.
It has been reported that lactate dehydrogenase virus (LDV) selectively infects a subpopulation of macrophages, thereby affecting the immune system. We studied the effects of LDV infection on the development of diabetes in non-obese diabetic (NOD) mice. Five-week-old female NOD mice were infected with LDV (10(8) ID50/mouse) and observed until 23 weeks of age. None of the 21-LDV-infected mice developed diabetes, whereas 10/14 (71.4%) uninfected mice did. Although the subpopulations of T cells and the percentage of Mac1-positive cells in the NOD murine spleen and the number of harvested peritoneal macrophages were unaffected by LDV infection, the proportions of Ia-positive peritoneal macrophages were significantly decreased in LDV-infected compared with uninfected mice (1.1 +/- 0.2%, 6.5 +/- 2.9%; P < 0.01). In LDV-infected NOD mice, insulitis of the same grade as that seen in uninfected NOD mice was observed. In another experiment, 3, 5, 10 or 16-week-old female NOD mice were infected with LDV. None of the mice infected with LDV at 3, 5 or 10 weeks of age developed diabetes and only one of six infected at 16 weeks of age did. These findings indicate that LDV infection suppresses the development of diabetes in female NOD mice by reducing the capacity of Ia-positive macrophages, and suggest that the development of human type 1 diabetes may be suppressed by certain viral infections.
Animals↗
Increases in NO2-/NO3- excretion in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure.
1. Under hormonally constant conditions, the effects of a sudden increase in blood pressure on the release of endothelium-derived relaxing factor were evaluated by measuring urinary excretion of NO2-/NO3- in rats with renal denervation. 2. Elevation of blood pressure from 136 +/- 2 to 153 +/- 3 mmHg by an aortic clamp below the renal arteries induced a significant increase in urinary excretion of NO2-/NO3- from 76.6 +/- 4.2 x 10(2) to 108.1 +/- 8.3 x 10(2) pmol min-1 g-1 kidney weight (P less than 0.05). 3. Infusion of NG-monomethyl-L-arginine (1 mg min-1 kg-1) without an aortic clamp raised mean blood pressure to a similar level; however, urinary excretion of NO2-/NO3- was decreased significantly. 4. During infusion of NG-monomethyl-L-arginine, aortic occlusion caused a significant increase in blood pressure without any changes in NO2-/NO3- excretion in the urine. 5. These results suggest that the formation of NO, an indicator of endothelium-derived relaxing factor release, was increased by mechanical pressure elevation without apparent changes in hormonal and neural factors.
Animals↗
Leisure time physical activity and insulin resistance in young obese students with hypertension.
To investigate the hypothesis that insulin resistance plays a role in the etiology of hypertension and hyperlipidemia, we measured serum lipid levels, the fasting glucose/insulin ratio, and the insulin response to oral glucose (GTT) in a group of young obese subjects (n = 21) with hypertension and normal glucose tolerance and in normotensive subjects (n = 36) with normal glucose tolerance, matched for age and body mass index. Leisure time physical activity was evaluated by a questionnaire outlining three levels of physical activities during leisure time. Subjects with hypertension had higher fasting serum insulin (19 +/- 2 v 13 +/- 1 microU/mL, P < .01) and lower fasting glucose/insulin ratio (5.3 +/- 0.2 v 7.1 +/- 0.5 mg/dL/microU/mL, P < .01) than normotensive subjects. Subjects with hypertension had higher peak serum insulin and lower plasma glucose area/insulin area ratio in response to glucose (1.8 +/- 0.2 v 2.4 +/- 0.2 mg/dL/microU/mL, P < .05) than normotensive subjects. Serum total cholesterol, low-density cholesterol, and triglycerides were higher in the obese hypertensive subjects than in obese normotensive ones. Blood pressure correlated with either fasting serum insulin, fasting glucose/insulin ratio, or glucose area/insulin area ratio during GTT. The level of leisure time physical activities was lower in obese hypertensive subjects than in obese normotensive ones. There were significant correlations between the levels of physical activity and the fasting plasma glucose/insulin ratio (r = 0.371, P < .01) or the fasting serum insulin concentration (r = -0.282, P < .05). The study provided evidence that a low level of leisure time physical activity is associated with insulin resistance and resultant hyperinsulinemia, which are the key metabolic abnormalities that link hypertension, obesity, and hyperlipidemia in young subjects.
Adolescent↗
Agranulocytosis in a haemodialysed patient induced by a proteinase inhibitor, nafamostate mesilate.
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Aged↗
Case report: hypertension in Cushing's syndrome.
Pathogenesis of hypertension in Cushing's syndrome has remained controversial. A 56-year-old Japanese man with Cushing's syndrome due to adrenal carcinoma has been followed up for more than 6 years. During the followup period, left adrenalectomy and hemihepatectomy due to metastatic lesion were performed. Blood pressure, serum cortisol, and urinary excretion of 17-OHCS, as well as other routine biochemicals, have been measured periodically. These data revealed that there is a marked correlation between the levels of blood pressure and serum cortisol or urinary excretion of 17-OHCS. This finding suggests that cortisol production by tumor is a determinant factor in hypertension in Cushing's syndrome.
Adrenal Gland Neoplasms↗
Depressor systems contribute to hypertension induced by glucocorticoid excess in dogs.
OBJECTIVE: The aim of this study was to investigate the role of depressor systems in glucocorticoid-induced hypertension. METHODS: The serial changes in cardiorenal hemodynamics, urinary excretions of kallikrein and prostaglandins (PGE2 and the prostacyclin derivative 6-keto-PGF1 alpha) before, and during the administration of both low and high doses of dexamethasone (9 alpha-fluoro-16 alpha-methylprednisolone) and after the cessation of dexamethasone were examined in conscious trained dogs. In addition, pressor responses to prostaglandin, bradykinin, bradykinin antagonist and indomethacin were studied during the administration of dexamethasone. RESULTS: High-dose dexamethasone induced a significant elevation in mean arterial pressure (MAP) that was accompanied by a significant reduction in the urinary excretion of kallikrein, PGE2 and 6-keto-PGF1 alpha. In contrast, low-dose dexamethasone treatment had no significant effect upon MAP but induced a transient elevation in the urinary excretion of kallikrein, PGE2 and 6-keto-PGF1 alpha. Furthermore, additional oral administration of indomethacin produced a significant elevation in MAP in dogs treated with low-dose dexamethasone; but did not affect the hemodynamics of animals with high-dose dexamethasone. Whilst i.v. administration of either bradykinin or prostacyclin induced a significant reduction in MAP in high-dose but not low-dose dexamethasone-treated dogs, administration of a competitive bradykinin antagonist, D-Arg-[Hyp3, Thi5,8, D-Phe7]-bradykinin induced a significant elevation in MAP in low-dose but not high-dose dexamethasone-treated dogs. CONCLUSION: Depressor systems play an important role in regulation of blood pressure in glucocorticoid-treated dogs.
Animals↗
Differential effects of captopril and nicardipine on baroreflex control of sympathetic nerve activity and heart rate in renal hypertension.
OBJECTIVE: To test the hypothesis that an angiotensin I converting enzyme inhibitor and a calcium channel blocker have different effects on the arterial baroreflex in renal hypertension. DESIGN AND METHODS: We examined the baroreflex control of renal sympathetic nerve activity and heart rate before and after blood pressure was reduced by a similar magnitude (11 +/- 1 mmHg) with intravenous captopril or nicardipine in two-kidney, one clip hypertensive (mean arterial pressure 92 +/- 2 mmHg, n = 12) and normotensive rabbits (mean arterial pressure 75 +/- 1 mmHg, n = 9) in the conscious state. Data obtained during activation and deactivation of baroreceptors were analysed with logistic function curves, and the maximum slope of the curve was taken as the sensitivity of the baroreflex. RESULTS: The maximum slopes of the curves relating mean arterial pressure to renal sympathetic nerve activity and to the heart rate in hypertensive rabbits were significantly smaller than the maximum slopes in normotensive rabbits. In renal hypertensive rabbits, the maximum slope of the mean arterial pressure-renal sympathetic nerve activity curve was increased with captopril compared with that with vehicle. In contrast, the maximum slope of the mean arterial pressure-heart rate curve was increased with nicardipine compared with that with vehicle. CONCLUSIONS: Our data indicating that the baroreflex control of renal sympathetic nerve activity was improved by captopril and that baroreflex control of the heart rate was potentiated by nicardipine suggest that these classes of antihypertensive agents had differential effects in conscious hypertensive rabbits.
Angiotensin II↗
New method of investigating functional roles of pressure-sensitive mechanoreceptor in human endothelial cells.
The role of pressure-sensitive mechanoreceptors (PSMRs) in histamine-stimulated nitric oxide release from cultured human endothelial cells was investigated, using our new method (helium pack method). PSMRs were stimulated by various levels of pressure applied in addition to atmospheric pressure (40, 80, 120, and 160 mm Hg). Histamine-stimulated nitric oxide release was inhibited in a pressure-dependent manner. Our results suggest that PSMRs modulate nitric oxide release from endothelial cells.
Cells, Cultured↗
L-arginine as an antihypertensive agent.
L-Arginine, the precursor of endothelium-derived relaxing factor (EDRF)/nitric oxide (NO), was administered intravenously in five patients with essential hypertension, one with renovascular hypertension, one with primary aldosteronism, and one with Cushing's syndrome. During the administration, the mean arterial pressure decreased concomitantly with an elevation of cardiac output and a fall in total peripheral resistance in all cases. Indicators of NO release in vivo such as plasma concentrations of L-citrulline and urinary excretion of nitrite/nitrate increased simultaneously during the administration. These results suggest that exogenous L-arginine can produce a vasodilatory effect via stimulating NO release in hypertensives.
Antihypertensive Agents↗
Dexamethasone potentiates production of inositol trisphosphate evoked by endothelin-1 in vascular smooth muscle cells.
To investigate the possibility of participation of glucocorticoids in the action of endothelin-1 (ET-1), the effect of glucocorticoids on ET-1-induced inositol trisphosphate (IP3) production was studied in cultured vascular smooth muscle cells (VSMC). ET-1 transiently increased IP3 in a dose-dependent manner. Pretreatment with 1 microM dexamethasone for 48 h shifted the dose-response curve of ET-1-induced IP3 production to the left; i.e., it significantly reduced the half-maximal effective concentration of ET-1 (from 50 to 10 nM). This action of dexamethasone required a minimum of 12 h of incubation. A glucocorticoid antagonist, RU 38486, completely blocked this effect. To elucidate the interaction with prostaglandin, we used indomethacin, a potent inhibitor of prostaglandin synthesis. Treatment with 1 microM indomethacin shifted the dose-response curve of ET-1-induced IP3 production to the left, but this shift was significantly less than that observed after treatment with dexamethasone and no additive effect between indomethacin and dexamethasone was noted. Glucocorticoids potentiate the IP3 production response to ET-1 in cultured VSMC, and this action of glucocorticoids depends partially on prostaglandin inhibition. These results suggest that glucocorticoids play an important role in modulation of ET-1 action.
Animals↗
Renal nerves contribute to salt-induced hypertension in sinoaortic-denervated uninephrectomized rabbits.
The objective of this study was to investigate the role of the renal nerves in the pathogenesis of salt-induced hypertension in sinoaortic-denervated uninephrectomized rabbits. Twelve rabbits were divided into two groups. Sinoaortic-denervated uninephrectomized rabbits with intact renal nerves (sham group: n = 6) and without renal nerves (RDN group; n = 6). In both groups, 2 days of 154 meq/l NaCl loading was followed by 10 days of 1,700 meq/l NaCl loading. We administered 154 meq/l or 1,700 meq/l NaCl intravenously at every 8 h. Serial changes in mean arterial pressure (MAP) and heart rate (HR) were recorded using a microcomputer system. We chronologically measured hematocrit, serum osmolality, serum sodium, potassium, and chloride concentration, serum creatinine, plasma renin activity, plasma aldosterone, plasma norepinephrine, plasma arginine vasopressin, and plasma atrial natriuretic peptide. Urine volume and body weight were recorded every day, as were urinary concentrations of sodium, potassium, and chloride. The basal value of MAP in the sham group was significantly higher than that in the RDN group (on day -2, 111 +/- 1 mmHg for sham, 99 +/- 2 for RDN, P less than 0.001). Hypertonic saline loading induced an elevation of blood pressure in the sham group (126 +/- 2 mmHg on day 4, 127 +/- 2 on day 7, 124 +/- 4 on day 10). There were no significant changes in the response to salt loading in the RDN group. In the sham group, the retention of sodium was significant compared with that in the RDN group on day 5, and this difference was maintained until the end of the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Chronic DOC treatment enhances Na(+)-H+ exchanger activity of beta-intercalated cells in rabbit CCD.
Chronic deoxycorticosterone (DOC) treatment is known to increase HCO3- secretion in rabbit cortical collecting ducts (CCD). In this study, we examined whether changes in number or function of intercalated cells (ICC) are induced by DOC treatment. The number of total ICC [acetoxymethyl ester of 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF/AM)-positive cells after its luminal loading], and beta-ICC (peanut agglutinin-positive cells) was not different between DOC and control groups in either initial CCD or terminal CCD. To evaluate the single-cell function of ICC, the rate of intracellular pH (pHi) recovery (dpHi/dt, pHU/s x 10(3)) after NH4+/NH3 prepulse was studied in the in vitro microperfused CCD in the presence of HCO3-/CO2 with BCECF/AM. The mean rate of dpHi/dt of beta-ICC in the DOC group was faster than that in the control group (6.19 +/- 0.36 vs. 4.30 +/- 0.41, P less than 0.005, respectively), whereas baseline pHi and buffer capacity were similar in the two groups. The inhibition of basolateral Na(+)-H+ exchanger with 1 mM amiloride eliminated the difference of dpHi/dt between the two groups, indicating the increased activity of basolateral Na(+)-H+ exchanger of beta-ICC in the DOC group. The correction of DOC-induced metabolic alkalosis by oral acid loading abolished the increase in Na+/H+ exchanger activity by chronic DOC treatment. These results suggest that DOC treatment induces a functional change in a single beta-ICC and that this functional change was induced by in vivo acid-base status.
Acids↗
Role of platelet cytosolic calcium in regulation of blood pressure in patients on chronic hemodialysis.
We measured blood pressure, platelet cytosolic calcium concentration ([Ca2+]i) and vasoactive hormones in 20 anuric normotensive patients on chronic hemodialysis (HD) to clarify the role of cytosolic calcium in regulation of blood pressure. All measurements were performed at the end of HD (post-HD) and at the beginning of the next HD (pre-HD). During the HD-HD interval, mean blood pressure increased from 85 +/- 4 to 94 +/- 4 mm Hg (mean +/- SEM, p less than 0.05), but the median [Ca2+]i in platelets did not show any significant change (133 +/- 5 vs. 136 +/- 5 nmol/l). Although all patients were within their ideal body weight at post-HD, platelet [Ca2+]i did not correlate with mean blood pressure. By contrast, platelet [Ca2+]i correlated with mean blood pressure (r = 0.489, p less than 0.05) at pre-HD. Moreover, platelet [Ca2+]i at post-HD also correlated with changes in mean blood pressure during the HD-HD interval (r = 0.532, p less than 0.05). In addition, there were negative correlations between platelet [Ca2+]i and plasma renin activity both post- and pre-HD (r = -0.652, p less than 0.005; r = -0.673, p less than 0.005; respectively). These results suggest that cytosolic calcium plays important roles in regulation of renin secretion and in the elevation of blood pressure induced by volume expansion in patients on chronic HD.
Adult↗
Potentiation of inositol trisphosphate production by dexamethasone.
One of the mechanisms of glucocorticoid-induced hypertension has been thought to be the enhancement of vascular responsiveness to vasoconstrictors. In this regard, the effects of glucocorticoids on inositol trisphosphate production in vascular smooth muscle cells were studied. Angiotensin II and arginine vasopressin transiently increased inositol trisphosphate formation in a dose-dependent manner. Pretreatment with dexamethasone for 48 hours shifted the dose-response trisphosphate curves of angiotensin II- and arginine vasopressin-induced inositol trisphosphate production to the left, that is, it significantly reduced the half-maximal effective concentrations of angiotensin II (from 25 nM to 5 nM) and arginine vasopressin (from 50 nM to 25 nM). These effects of dexamethasone required a minimum of 12 hours of incubation; maximum effect was observed after 24 hours of treatment. A glucocorticoid antagonist, RU 38486, completely blocked these effects. To elucidate the interaction with prostaglandin, we used indomethacin, a potent inhibitor of prostaglandin synthesis. Treatment with indomethacin shifted the dose-response curves of angiotensin II- and arginine vasopressin-induced inositol trisphosphate production to the left. However, this shift was less than that seen after dexamethasone treatment. Indomethacin alone did not completely reproduce dexamethasone effects, and no additive effect between indomethacin and dexamethasone was observed. These results suggest, at least in part but not entirely, that the effects of dexamethasone depended on prostaglandin synthesis inhibition. We concluded that glucocorticoids altered the responsiveness of vascular smooth muscle cells to angiotensin II and arginine vasopressin through a glucocorticoid-specific receptor. These actions strongly support the mechanism by which the glucocorticoid induced hypertension through the increased sensitivity to vasoconstrictors.
Angiotensin II↗
Disturbed calcium metabolism in offspring of hypertensive parents.
To assess a possible heritability of a disturbed calcium metabolism in relation to blood pressure regulation, 28 young normotensive offspring of either hypertensive or normotensive parents were studied while administered a defined diet with daily sodium chloride of 6 and 20 g/day for 7 days each. Before the high salt diet was begun, the cytosolic calcium concentration ([Ca2+]i) in platelets was elevated in offspring of hypertensive parents, whereas serum electrolytes, plasma renin activity, plasma catecholamines, and 24-hour urinary excretion of sodium and calcium showed no difference between the two groups. On exposure to a high salt diet, the mean blood pressure increased (from 80 +/- 2 to 85 +/- 2 mm Hg, p less than 0.05) in offspring of hypertensive parents. These changes in mean blood pressure were positively correlated with the basal platelet [Ca2+]i (r = 0.61, p less than 0.01), whereas [Ca2+]i did not demonstrate any significant changes. When the subjects were administered the high salt diet, plasma ionized calcium decreased (from 2.37 to 2.21 meq/l, p less than 0.05) and 1,25-dihydroxyvitamin D3 increased (from 32.7 to 40.8 pg/ml, p less than 0.05) with a transient relative hypercalciuria in offspring of hypertensive parents. This increase of 1,25-dihydroxyvitamin D3 was significantly correlated with the changes in mean blood pressure (r = 0.62, p less than 0.01). Disturbed intraplatelet and systemic calcium metabolism may be of predictive value in the development of hypertension.
Adolescent↗