Toshio Morise

Vascular complications in patients with aldosterone producing adenoma in Japan: Comparative study with essential hypertension

The incidence of vascular complications in 224 patients with aldosterone-producing adenoma (APA) which was proven on adrenal surgery, was compared to that in 224 sex- and age-matched patients with essential hypertension (EHT). The incidence of cerebral hemorrhage was significantly higher (p<0.05) in the patients with APA when compared to the EHT group. On the other hand, the incidence of myocardial infarction and/or congestive heart failure in the APA group was lower, although this difference did not reach statistical significance. Diastolic blood pressure in the APA group was significantly higher (p<0.001) in the EHT group. However, a significant difference in diastolic blood pressure was not detected between the APA groups with and without vascular complications, whereas in the EHT group diastolic blood pressure was significantly higher (p<0.001) in cases with vascular complications as compared to those without complications. As a possible factor contributing to the higher incidence of cerebral hemorrhage in the APA group, proteinuria was suggested. It was recommended that patients with primary aldosteronism should undergo operation when localization of the APA is established.

Increased Plasma Levels of Immunoreactive Endothelin and von Willebrand Factor In NIDDM Patients

OBJECTIVES To elucidate the significance of plasma levels of endothelin (ET) and von Willebrand factor (vWF) as possible markers for endothelial dysfunction in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS Plasma levels of ET and vWE were determined in 22 NIDDM patients with or without retinopathy and 10 normal control subjects. RESULTS The plasma levels of immunoreactive endothelin (irET) and vWF in NIDDM patients were 0.78 ± 0.06 pmol/1 and 218.3 ± 18.4%, respectively, which represented significant (P < 0.05, P < 0.01, respectively) differences from the values in the control group (0.50 ± 0.06 pmol/1 and 139.1 ± 11.1%, respectively, n = 10). However, when the diabetic patients were divided into two groups according to the presence or absence of diabetic retinopathy, the plasma levels of irET and vWF in the NIDDM patients with retinopathy were significantly higher (1.01 ± 0.07 pmol/1 and 283.0 ± 21.4%, respectively, n = 12) compared with the control group and NIDDM patients without retinopathy (0.59 ± 0.06 pmol/1 and 164.3 ± 17.0%, respectively). Plasma levels of irET showed a significant (P < 0.01) positive correlation with the levels of vWF. CONCLUSIONS These data strongly suggest that increased plasma irET reflects the endothelial cell damage in NIDDM.

Rapid detection and prevalence of the variants of the angiotensinogen gene in patients with essential hypertension

Abstract. Objectives. The angiotensinogen (AGT) gene has been implicated as a candidate gene of high blood pressure. However, because the variants of the AGT gene are point mutations, it is difficult to detect them in large scale population studies. The aims of this study were to develop a rapid screening method for the point mutations and, using this method, to determine the possible role of the AGT gene variant in high blood pressure in the Japanese population.

Stimulation of atrial natriuretic peptide secretion and synthesis by Na-K-ATPase inhibitors

Ouabain has been reported to increase the secretion of ANP in vitro. In this study, we focused on whether this action is common in Na-K-ATPase inhibitors (ATPI) and whether ATPI simply increase the release of ANP or stimulate both its biosynthesis and release. The effects of ouabain and digoxin on secretion of ANP and accumulation of ANP mRNA were investigated in the rat cardiocyte superfusion system. Ouabain and digoxin increased the immunoreactive ANP (iANP) output into perfusate and accumulation of ANP mRNA significantly. These results suggest that ATPI may stimulate both ANP biosynthesis and release in vitro.

Participation of Vascular Prostacyclin for the Pathogenesis of Experimental Glucocorticoid Hypertension in Rats

Prostacyclin (PGI2) generation in the mesenteric arteries from dexamethasone acetate (DX) and deoxycorticosterone acetate (DOCA) treated rats was assessed by ex vivo perfusion method. PGI2 generation which was measured by 6-keto-PGF1 alpha output in the perfusate was significantly reduced in DX treated rats at prehypertensive stage both under the basal conditions and in response to angiotensin (ANG) II, whereas in DOCA group rats, vascular PGI2 production was not impaired. Plasma renin activity (PRA) was significantly suppressed in DOCA but normal in DX rats. These results suggest that the reduced PGI2 generation in the resistance arteries may contribute to the development of hypertension induced by DX.

Frequency of Renin Gene Restriction Fragment Length Polymorphism in Hypertensives with a Genetic Predisposition to Hypertension

The genetic basis of essential hypertension is still uncertain. Because renin is thought to be a candidate gene for essential hypertension, a prospective study was conducted to compare the frequency of renin gene HindIII restriction fragment length polymorphism (RFLP) in normotensive and hypertensive subjects without (HTG-) and with a genetic predisposition to essential hypertension (HTG+). The frequency of the 9.0-kb fragment was significantly (p < 0.05) higher in the HTG+ group than in the normotensive and HTG- groups. An association between renin RFLP and hypertension in man was shown for the first time. It is suggested that a gene for blood pressure regulation has been localized to a part of the genome close to, or identical to, the renin locus.

Increased plasma endothelin levels in Kawasaki disease: a possible marker for Kawasaki disease.

Plasma immunoreactive endothelin (iET) levels were investigated in patients with Kawasaki disease (KD). The iET level was 2.49 ± 0.13 pg/mL in KD pa tients and 1.32±0.06 in age-matched control subjects, showing a significant increase with KD. The iET level was not increased in patients with febrile in flammatory diseases of bacterial origin without KD (non-KD group). Parame ters indicating an inflammatory reaction, such as C-reactive protein, platelet count, white blood cell count, and interleukin-6 level, were increased in the KD patients. However, they were similarly increased in the patients with febrile diseases of bacterial origin and showed no significant differences between the two groups. This study is the first to report that plasma iET levels are elevated in a disease mainly involving vasculitis. These results suggest that blood iET levels are increased in KD patients as a result of the associated vascular endo thelial damage and that iET can be a useful marker for the diagnosis of KD.

Possible association of aldosterone producing adenoma and non-functioning adrenal tumor

A 37-year-old woman presented with hyperaldosteronism, suppressed renin levels, and a left adrenal mass on CT scanning. Selective adrenal venous sampling indicated a marked rise of the aldosterone level in the right adrenal vein, while the level in the left vein was low. On laparotomy, an aldosterone producing adenoma (APA) of 12×10×5 mm in size was found in the right adrenal gland and was resected, while the left mass was left in situ. The post-operative course showed normalization of both the clinical and biochemical features of primary aldosteronism, with no sign of recurrence or of enlargement of the remaining adrenal mass in 2.5 years of follow up, suggesting the possible coexistance of a “non-functioning” tumor. This case demonstrates the importance of adrenal venous sampling for the localization of APA particularly since the presence of the APA may be masked by a visualized but unrelated adrenal mass.

Plasma aldosterone response to angiotensin II in sodium-restricted elderly subjects with essential hypertension.

The plasma aldosterone (PA) response to sodium restriction (25 mEq daily for 4 days) and to graded infusions of angiotensin II (AH, 2, 4 and 8 ng/kg/min each for 30 min) during a low‐sodium intake were studied in 15 elderly subjects with mild essential hypertension versus 10 elderly normotensive subjects. The PA reponse to sodium restriction relative to changes in plasma renin activity (PRA) was estimated by the ratio of PA increment to PRA increment after sodium restriction (ΔPA/ΔPRA). The PA response to graded AII infusions was determined by the increment of PA above the basal level after each dose of AII. In 10 of the 15 elderly hypertensive subjects whose PRAs responded normally to sodium restriction, the ΔPA/ΔPRA ratios and PA increments during the graded AII infusions were similar to those in the elderly normotensive subjects. However, in the remaining 5 elderly hypertensive subjects whose PRAs responded subnormally to sodium restriction, the ΔPA/ΔPRA ratios were high and the PA increments greater during the graded AII infusions. The increments of mean blood pressure during the graded AII infusions were similar in the foregoing 10 of 15 hypertensive subjects, and significantly greater during the AH infusion rates of 4 and 8 ng/kg/min in the remaining 5 hypertensive subjects when compared with those in the normotensive subjects. Apparently some elderly subjects with essential hypertension, whose PRAs respond subnormally to sodium restriction, have an abnormally enhanced adrenal responsiveness to AII under the condition of low‐sodium intake.

A new variant deletion of a copper-transporting P-type ATPase gene found in patients with Wilson's disease presenting with fulminant hepatic failure

Abstract: A candidate gene (ATP7B) for Wilsons disease, an autosomal recessive disorder of copper transport, has recently been identified. We examined the ATP7B gene in two Japanese sisters with Wilsons disease presenting with fulminant hepatic failure but who did not exhibit Kayser-Fleischer rings or abnormal neurological findings. Genomic DNA was isolated from the whole blood of the patients and their family. Entire exons of ATP7B, and their associated splice junctions, were amplified by polymerase chain reaction. The sequencing of all exons was performed by a non-radioactive sequencing method. The sequencing of exon 12 of ATP7B revealed a 9-bp deletion. The mutation deleted 922Gly, 923Tyr, and 924Phe, and three residues conserved in the Menkes gene, ATP7A, located in the fifth transmembrane region. Of the 14 family members tested, 7 were normal and 7 were heterozygous for the deletion. Mean serum copper and cerulopasmin levels were significantly lower in the family members who were heterozygous for the deletion than in the normal family members, and two heterozygous family members showed abnormally low ceruloplasmin levels; however, there were no differences in mean aspartate aminotransferase or alanine aminotransferase levels between the two groups.