Variant forms of primary aldosteronism: reconsideration of the differential diagnosis and treatment.
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Diagnosis, Differential↗
Biomedical subjects
A Tanabe
Publications and source records attributed to A Tanabe.
[Pseudohypoaldosteronism].
Mineralocorticoid resistance results from inability of aldosterone to exert its effect on its target tissues. The syndrome is associated with salt loss, hypotension and hyperkalemic acidosis. We have cloned and sequenced the cDNA of the mineralocorticoid receptor of five sporadic cases with this syndrome but have found no mutations of pathophysiological significance, which would explain the resistance of these patients to aldosterone. In all of these patients, we also examined 0.9 kb of the 5' regulatory region and the first untranslated exon of the mineralocorticoid receptor gene, without detecting any abnormalities. We are now studying the subunits of the amiloride-sensitive sodium channel (ENaC), which are in the postreceptor pathway of aldosterone action, in this disease.
Aldosterone↗
[Juxtaglomerular cell tumor].
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Adenocarcinoma↗
Differential gene expression of vascular natriuretic peptide receptor subtype in artery and vein.
Although the vasorelaxation by natriuretic peptide (NP) is much less potent in the vein than in the artery, mechanism underlying the phenomenon remains unknown. Since NP receptor consists of three subtypes with different functions, we determined the mRNA level of each NP receptor subtype in the artery and vein by ribonuclease protection assay. In the aorta, NP-A receptor related to the biological action of NP was the predominant form. By contrast, NP-C receptor related mainly to the clearance of NP was the predominant form in the inferior vena cava: NP-C mRNA level was about two fold higher than in the aorta, while both NP-A and NP-B receptor mRNA levels were about half of that in the aorta. These results provide the molecular basis for the different biological response to NP in the artery and vein. Differential gene expression of NP receptor subtype could be an important determinant of the biological actions of NP.
Animals↗
Gene expression of vascular natriuretic peptide receptor in the aorta of hypertensive rats.
1. To elucidate the pathophysiologic role of vascular natriuretic peptide (NP) receptor in hypertension, we determined NP-A and NP-B receptor mRNA levels by means of ribonuclease protection assay in aorta of three types of hypertensive rats. 2. The NP-A receptor mRNA level was higher in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and deoxycorticosterone acetate-salt hypertensive rats than that in their respective control rats. On the contrary, the NP-A receptor mRNA level was lower in NG-nitro-L-arginine-methyl ester (L-NAME)-induced hypertensive rats compared with that in the control. 3. The NP-B receptor mRNA level did not show any significant change in all three hypertensive rats compared with their respective controls. 4. The present study suggests that high blood pressure is not the major factor regulating the NP receptor gene expression and also that the receptor subtype is independently regulated from each other.
Animals↗
Modulation of vascular natriuretic peptide receptor gene expression in hypertensive and obese hyperglycemic rats.
Receptors for natriuretic peptide (NP) consist of three subtypes: NP-A, NP-B, and NP-C. Recent studies in cultured aortic cells have suggested a phenotype-related switching of the vascular NP receptor from NP-A to NP-B. To ascertain the biological significance of the phenomenon in vivo, we developed a sensitive and reproducible ribonuclease protection assay and determined each receptor messenger RNA (mRNA) level in the vascular vessels of stroke-prone spontaneously hypertensive rats, deoxycorticosterone acetate-salt hypertensive rats, and genetically hyperglycemic. Wistar fatty rats and in cultured aortic smooth muscle cells. The aortic NP-A receptor mRNA level was significantly up-regulated in both types of hypertensive rats, whereas the NP-B receptor mRNA level did not show any significant change. Both NP-A and NP-B receptor mRNA levels were significantly up-regulated in Wistar fatty rats compared with the control values. There was no significant up-regulation of NP-A receptor mRNA in the inferior vena cava of the stroke-prone spontaneously hypertensive rats. Although the NP-A receptor was always the predominant subtype in rat aortic tissue, NP-B receptor was the predominant subtype in aortic smooth muscle cells in culture. These findings suggest that up-regulation of the NP-A receptor, but not the subtype switching, is the major modulation of receptor gene expression in both hypertensive and diabetic rats.
Animals↗
Dopaminergic regulation of aldosterone secretion: its pathophysiologic significance in subsets of primary aldosteronism.
Although aldosterone (Aldo.) secretion is regulated by various humoral factors, evidence has accumulated to support an involvement of dopaminergic system in its regulation. The pathophysiological significance of the dopaminergic system in primary aldosteronism (PA) however remains unknown. In the present study, we examined the effects of metoclopramide (MCP) on Aldo. secretion in normal subjects (n = 11) and patients with essential hypertension (EH, n = 8), aldosterone-producing adenoma (APA, n = 10), and idiopathic hyperaldosteronism (IHA, n = 6). Plasma Aldo., prolactin (PRL), renin, cortisol, serum sodium, and serum potassium levels were determined before and 30 min after i.v. bolus injection of 10 mg MCP at 9 a.m. Plasma Aldo. showed a significant increase after MCP in normal subjects, EH, and APA, but not in IHA. The incremental response of plasma Aldo. was largest in APA and smallest in IHA. The percentage increase in plasma Aldo. from the basal level was significantly attenuated in IHA, while no significant difference was seen among other groups. Although plasma PRL showed a significant increase in response to MCP, no difference of the change was seen among the groups. There was no significant change in plasma cortisol, renin, serum sodium, and serum potassium levels in response to MCP. In addition, the response of Aldo. to MCP was normalized in APA after unilateral adrenalectomy, while that of PRL did not change. These results indicate that the adrenal dopaminergic activity is enhanced in APA and attenuated in IHA and suggest an involvement of the dopaminergic system in the pathogenesis of IHA.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
Effects of acute hyperinsulinemia on plasma atrial and brain natriuretic peptide concentrations.
Impaired renal sodium excretion and increased plasma atrial natriuretic peptide (ANP) levels have been reported in patients with hypertension associated with insulin resistance and hyperinsulinemia. To clarify the interrelationship between hyperinsulinemia and plasma natriuretic peptides, we investigated the effects of physiological and non-physiological hyperinsulinemia on the plasma ANP and brain natriuretic peptide (BNP) levels. Plasma immunoreactive insulin (IRI), ANP and BNP levels were determined by a euglycemic-hyperinsulinemic glucose clamp in 20 patients with non-insulin-dependent diabetes mellitus, by a glucose challenge test in 22 normal subjects and by an insulin challenge test in six normal subjects. Both in the glucose clamp and the glucose challenge test, plasma ANP showed a significant increase in association with increased plasma IRI and plasma volume. However, there was no significant correlation between the changes in plasma ANP levels and plasma IRI levels in view of the peak values and the area under the curve of their responses. In addition, the plasma ANP did not show any significant change despite the marked elevation of plasma IRI in the insulin challenge test. There was no significant change in plasma BNP under any of the hyperinsulinemic conditions. These findings provide in vivo evidence for the lack of a direct effect of acute hyperinsulinemia on natriuretic peptides, although the chronic effects of hyperinsulinemia remain to be elucidated.
Acute Disease↗
[Fontan-type procedure for an adult case of double-outlet right ventricle (S, D, L)].
The double-outlet right ventricle with L-malposition (DORV (S, D, L)) is one of the rare congenital heart diseases. Intracardiac rerouting with a internal conduit has been indicated in principle to it as the radical operation. DORV (S, D, L) is often combined with the pulmonic stenosis (PS), and Rastelli's operation is indicated to the case in which release of PS is difficult. We report a case of DORV (S, D, L) combined with PS and the hypoplastic right ventricle which is treated by the Fontan-type procedure. The patient was a 35-year-old female who had undergone Glenn's operation at 10 years of age under the diagnosis of transposition of the great arteries. Recently she complained of aggravation of the cyanosis and dyspnea on exertion. After thorough examinations, the disease was diagnosed as DORV (S, D, L) with doubly committed VSD which was combined with severe PS, hypoplastic right ventricle (29% of normal) and left-sided juxtaposition of atrial appendages. The development of her distal pulmonary arteries was estimated well enough (PA-index 448 mm2/m2). We judged that intracardiac rerouting with an internal conduit could not be applied due to her severe pulmonic stenosis, and that Rastelli's operation as the biventricular repair was also impossible because of her hypoplastic right ventricle. Thus we adopted the Fontan-type procedure with a new septation in the right atrium, namely oblique partition, and attained a good result. To our knowledge, this case is the fourth case report in Japan of DORV (S, D, L) treated with the Fontan-type procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Inhibitory effects of Forskolin on hepatic metastasis from human colon cancer in nude mice].
Platelet aggregation has been believed to play an important role in implantation of tumor cells into the target organ during the early phase of tumor metastasis. In the present study, the effects of Forskolin, a strong platelet aggregation inhibitor, on experimental hepatic metastasis from human colon cancer (HT29LMM) in nude mice and inhibitory effects of Forskolin on platelet aggregation in the presence of tumor cells were evaluated. A hepatic metastasis model was established by intrasplenic implantation of 3-4 x 10(6) of HT29LMM human colon cancer cells in nude mice. Intraperitoneally 10mg/kg of Forskolin was given 30 minutes before and 24 hours, after implantation of tumor cells, respectively. The control group received saline instead of Forskolin. Phase of hepatic metastasis has been compared for the total weight of hepatic metastatic lesions and the occupied rate between the Forskolin-given group and the control group. The total weight of hepatic metastasis lesions (0.36 +/- 0.33g (SD) vs 3.36 +/- 1.31g) and the occupied rate (8.22 +/- 7.91% vs 67.9 +/- 23.2%) were significantly low in the Forskolin-given group compared with the control group. In vitro inhibitory effects of Forskolin on platelet aggregation was recognized under the presence of HT291LMM. This study suggests that the platelet aggregation inhibitor drug. Forskolin, inhibits hepatic metastasis from human colon cancer by preventing platelet aggregation during the metastatic tumor formation.
Animals↗
Angiotensin converting enzyme inhibitor but not calcium blocker down-regulates gene expression of vascular natriuretic peptide receptor in hypertensive rats.
We have recently found that vascular natriuretic peptide (NP)-A receptor mRNA is upregulated in genetically hypertensive (SHR-SP/Izm) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In the present study, we examined the effects of antihypertensive treatments on aortic NP-A receptor mRNA expression in these hypertensive rats using ribonuclease protection assay. Oral administration of an angiotensin converting enzyme inhibitor, derapril, but not a calcium channel blocker, manidipine, produced a significant decrease of the NP-A receptor mRNA level after 4 weeks, while both antihypertensive agents showed similar hypotensive effects. Plasma renin was high in SHR-SP/Izm and low in DOCA-salt rats. These results suggest that the vascular renin-angiotensin system rather than the blood pressure has an important role in the regulation of the vascular NP-A receptor.
Animals↗
[Clinical significance of nitric oxide in hypertension].
Vascular endothelial cells produce various biologically active factors regulating blood pressure, coagulation, and possibly cell growth of the vascular wall. Of the factors, nitric oxide (NO) has been the object of attention because of its quite simple molecular structure and variety of biological functions. In the present review, we focused on the physiologic and pathologic aspects of NO in hypertension. In experimental animals, both acute and chronic inhibition of NO synthase (NOS) with arginine derivatives produce a significant rise in blood pressure, indicating that tonic production of NO regulates basal vascular tonus. The chronic hypertension caused by NOS inhibitor is associated with cardiac hypertrophy and renal insufficiency. Sodium retention, though transient, and the plasma and tissue renin/angiotensin system in addition to the reduced production of NO have been implicated in the development of hypertension. Hypertension and the associated target organ failure can be reversed by co-administration of L-arginine or blockades of the renin/angiotensin system. Studies in which L-arginine as the substrate of NO or NOS inhibitor was administered demonstrated an important role of NO in the regulation of tonic vascular tonus also in normal subjects. In hypertensive subjects, however, endothelium-dependent vasorelaxation and production of NO are impaired, possibly due to a deficiency of L-arginine and/or a disorder of its utilization. Recent advances in the methods of detecting NO enabled us to demonstrate its diminished production from endothelial cells of hypertensive rats in vitro, although no definite biochemical evidence has been obtained in hypertensive subjects. The endothelial dysfunction, however, is not a primary cause of hypertension but a secondary result since it is commonly observed in various types of hypertension and can be reversed by correcting the blood pressure. Other common diseases including atherosclerosis and diabetes mellitus are also associated with similar abnormalities of the endothelium. NO has anti-atherogenic actions: inhibition of platelet functions and proliferation of vascular smooth muscle cells. Therefore, potentiation of endogenous NO and/or supplement of exogenous NO donors could be novel therapeutic approaches for the treatment of hypertension and atherosclerosis, while potential adverse effects of NO including cytotoxicity, immunosuppressibility, and hypotensive shock should be taken into account.
Amino Acid Oxidoreductases↗
A cranial invasion model of human neuroblastoma using congenitally athymic mice.
Even though the current limits of treatment for advanced stage neuroblastoma require an understanding of biology and new therapeutic approaches, few invasion models of human neuroblastoma (HNB) which evaluate experimental therapies have been reported. We describe herein a reproducible murine model of cranial invasion after the intraocular xenograft of HNB in congenitally athymic mice. Approximately 10 weeks after the intraocular injection of 5 x 10(6) NB-1 HNB cells, 70% (14/20) of the mice developed intracranial invasion with skull involvement. There was no operative mortality. Macroscopically, deformities of the cranium were revealed in all 14 mice, 5 of which developed exophthalmos. Microscopically, cranial invasion mainly involved the extradural space, skull, and orbita; however, brain involvement could not be seen, indicating that the dura may act as a barrier. These invasive characteristics are very similar to those seen in humans; thus, we believe that this model provides a useful tool for evaluating the biology of, and new therapeutic approaches against, cranial invasion of neuroblastoma in vivo.
Animals↗
Does plasma immunoreactive ouabain originate from the adrenal gland?
It was reported recently that the endogenous digitalis-like factor ouabain may mainly originate from the adrenal gland. To ascertain the pathophysiological significance of endogenous ouabain and to examine if it originates in the adrenal gland, we determined plasma immunoreactive ouabain levels in patients with various cardiovascular and endocrine diseases. Plasma immunoreactive ouabain levels were also determined in the adrenal venous blood by adrenal venous sampling. Plasma immunoreactive ouabain levels were significantly increased in patients with essential hypertension, primary aldosteronism, Cushing's syndrome, pheochromocytoma, acromegaly, and chronic renal failure. Plasma immunoreactive ouabain levels were decreased in patients with primary aldosteronism after unilateral adrenalectomy, acromegaly after pituitary adenomectomy, and chronic renal failure after hemodialysis. Plasma immunoreactive ouabain levels in patients after bilateral adrenalectomy were similar to those in healthy subjects. There was no significant step-up of immunoreactive ouabain levels in the adrenal vein from the peripheral vein in three patients, whereas one patient with hypertension and right adrenal tumor but without any known adrenal hormone excess showed higher plasma immunoreactive ouabain levels in the right adrenal vein than those in the peripheral vein. These results suggest an important pathophysiological significance of endogenous ouabain in various cardiovascular and endocrine diseases. It is unlikely that the adrenal gland is a major source of plasma ouabain, although a possible excess production of ouabain by the adrenal tumor remains to be elucidated.
Adrenal Gland Neoplasms↗
Atrial and brain natriuretic peptides in cardiovascular diseases.
The human heart secretes both atrial natriuretic peptide and brain natriuretic peptide. This study attempts to clarify the pathophysiological significance of the peptides in cardiovascular diseases. Using immunoradiometric assay, plasma brain natriuretic peptide and atrial natriuretic peptide levels in essential hypertension, various secondary hypertension, chronic renal failure, chronic heart failure during cardiac pacing, and acute myocardial infarction were determined. Mean plasma brain natriuretic peptide and atrial natriuretic peptide levels in healthy subjects were 3.7 +/- 0.3 and 5.7 +/- 0.3 pmol/L, respectively, and increased as a function of age. Plasma brain natriuretic peptide levels showed a larger increase than atrial natriuretic peptide levels in various cardiovascular diseases. In chronic renal failure, whereas plasma atrial natriuretic peptide levels decreased significantly after hemodialysis and were correlated with the changes in body weight, changes in plasma brain natriuretic peptide levels were less prominent and did not show such a correlation. In chronic heart failure, both basal plasma brain natriuretic peptide and atrial natriuretic peptide levels were also significantly elevated. However, in response to acute ventricular or atrial pacing, brain natriuretic peptide levels did not show any increase in contrast to the marked increase of atrial natriuretic peptide levels. In acute myocardial infarction, brain natriuretic peptide levels showed more prominent changes than atrial natriuretic peptide levels and were correlated with serum levels of creatine kinase and cardiac myosin light chain I in most patients. These results suggest that both brain and atrial natriuretic peptides play an important role in the regulation of cardiovascular homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Gland Neoplasms↗
[Evaluation of long-term efficacy of antiarrhythmic drug--an interium report of Japanese Antiarrhythmics Long-term Trial (JALT-1)].
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Anti-Arrhythmia Agents↗
[A case of emergent surgical salvage for the mitral prosthetic perivalvular leakage diagnosed only by the transesophageal Doppler echocardiography].
A case of the successful emergency surgery for the mitral prosthetic perivalvular leakage (PVL) which was diagnosed only by the transesophageal Doppler echocardiography (TEE) is reported. A 59-year-old male who had been diagnosed MS + TR + severe PH underwent mitral valve replacement with St. Jude medical valve 27 M. On the eighteenth postoperative day hemoglobinuria was noticed suddenly. Subsequently hemolysis and nonoriguric renal failure was aggravated, then we suspected PVL, but heart murmur was not audible or PVL could not been detected by the transthoracic echocardiography (TTE). PVL was detected for the first time by the TEE, then open heart resuture was emergently performed. The site of the PVL was the portion where the anterior mitral annulus adjoined the aortic annulus, that is, adjacent to the right fibrous trigone. This site is the portion which a surgeon should treat very carefully and where the PVL is very difficult to detect by the TTE. In regard to the detection of the PVL in mitral position, the TEE, which has ultrasonically no flow masking by the mitral prosthesis, is the very useful diagnostic means.
Echocardiography, Doppler↗
Quantitative analysis of distribution and fate of human lung cancer emboli labeled with 125I-5-iodo-2'-deoxyuridine in nude mice.
The chemical and radio toxicity of 125-5-iodo-2'-deoxyuridine (125IUDR) on 870127T human lung cancer (HLC) cells grown in tissue cultures and the quantitative analysis of the distribution and fate of 125IUDR-labeled 870127T HLC cells in nude mice were evaluated. After 870127T HLC cells were plated and 125IUDR was added to the dishes at levels ranging from 0.1 microCi/ml to 5.0 microCi/ml of media, the growth rate of the cells for 24 h was similar to that of non-labeled cells. Nude mice were given intravenous injections of 125IUDR labeled 870127T HLC cells and killed at various intervals ranging from 5 min to 24 h after injection. Organs were collected, processed, and monitored. The lung contained most of the tumor cells at all intervals and the number of tumor cells in the lung decreased gradually post-injection. The tumor cells died rapidly, and only about 1.5% of all cell survived after 24 h post-injection. This study confirmed that very few surviving tumor cells are needed to cause metastasis.
Adenocarcinoma↗