Mitsuhiro Gotoh

High Blood Pressure, Bone-Mineral Loss and Insulin Resistance in Women

Increasing evidence indicates that high blood pressure is associated with abnormalities in calcium metabolism. Sustained calcium loss may lead to increased bone-mineral loss in subjects with elevated blood pressure. Furthermore, recent findings indicate a possible linkage between abnormal calcium metabolism and insulin resistance. In the present study, we investigated the relationship(s) among bone-mineral density (BMD), blood pressure, calcium-related and bone metabolic parameters (plasma intact parathyroid hormone (I-PTH), 1,25-dihydroxyvitamin D [1,25(OH)2D], osteocalcin, and urinary deoxypyridinoline), and insulin resistance, as assessed by a conventional homeostasis model (HOMA-R). We compared non-diabetic women with essential hypertension (WHT, n=34) with age-, body mass index- and menopause (yes or no)-matched normotensive, non-diabetic women (WNT, n=34). The BMD for WHT was significantly lower than that for WNT (0.596±0.019 vs. 0.666 ±0.024 g/cm2, p<0.05). The BMD was correlated inversely with systolic blood pressure in all subjects examined (r=-0.385, p<0.05). The 24-h urinary calcium/sodium excretion ratio (Ux-Ca/Na) was significantly greater in WHT compared with WNT (p<0.01). In addition, a negative relationship was apparent between Ux-Ca/Na and BMD (r=-0.58, p<0.05). The plasma levels of PTH and 1,25(OH)2D, and HOMA-R were significantly higher in WHT compared with WNT (p<0.01, p<0.05, and p<0.05, respectively), whereas the serum ionized calcium was lower in WHT compared with WNT (p<0.05). There were no significant differences in serum total calcium, inorganic phosphorus, osteocalcin, or urinary deoxypyridinoline between the two groups. These results indicate that high blood pressure is associated with abnormalities in calcium metabolism and insulin resistance in WHT.

Evidence for the existence of inactive arterial renin in the rat

Inactive renin in rat arterial walls was investigated according to the following experiments. Dialysis at pH 7.4 following dialysis at pH 3.3 of the arterial tissue resulted in a significant rise of renin activity, from a control value of 0.41 +/- 0.07 to 0.62 +/- 0.06 ng/ml/h (p less than 0.01). Treatment with trypsin of the arterial tissue caused a rapid and apparent increase in the renin activity at either 0 or 27 degrees C. The molecular weight of the active renin was estimated to be 32,000 or 39,000, while that of the inactive renin was found to be 36,000 or 44,000 on Sephadex G-100 gel filtration. The contents of the inactive renin varied with different segments of arterial wall. The ratio of inactive renin to total renin was the lowest in renal artery wall (0.32), while there was no significant difference in the ratio in other arterial walls (abdominal aorta, 0.87; thoracic aorta, 0.93; carotid artery, 0.96; mesenteric artery, 0.89; pulmonary artery, 0.92). These findings suggest that conversion of inactive renin into active renin can occur in arterial tissue, which, in turn, plays an important role in the local control of vascular tone. It seems that inactive renin found in the arterial wall is of local origin.

[A case of congenital lipoatrophic diabetes with conjunctival pseudolymphoma and Sjögren's syndrome].

症例, 30才,女.生下時より全身の脂肪萎縮著明. 27才時糖尿病を指摘. 29才時右結膜仮性リンパ腫にて放射線療法施行. 1982年6月全身の脂肪萎縮の精査のため当科入院.検査所見:血沈亢進,白血球減少, RAテスト陽性,高γグロブリン血症.血清脂質正常. GTTにて糖尿病型, IRIは遅延反応.インスリン感受性低下.尿中diabetogenic peptide陽性. HGH, LHおよびFSHはそれぞれアルギニン, LH-RH負荷に対し遅延反応.以上より本症例を脂肪萎縮性糖尿病と診断した. 1984年5月ごろより口内乾燥感・両側膝関節痛出現, Sjoren症候群を合併すると診断した.現在までかかる症例の報告はなく,本疾患の発症・維持に免疫機構の異常を示唆した点で興味深い.

Biochemical properties of renin in human pituitary tissue

The biochemical properties of renin, extracted from human pituitary specimens obtained at autopsy, were studied using a specific antirenin antibody raised against human kidney renin. The following results were obtained. The molecular weight of pituitary renin was estimated to be about 37,000 daltons by gel filtration through Sephadex G-100. The optimum pH of pituitary renin was between 6.0 approximately 7.0, while that of a renin-like substance which did not react with the antirenin antibody had an acidic pH of 4.0, with a pH comparable to that of the cathepsin D-like enzyme in the pituitary tissue. The presence of two different isoelectric-point species of pituitary renin was revealed by isoelectric focusing, one with a point of pH 4.47 and the other with that of pH 5.77. The Km value of pituitary renin was 37.9 microM for synthetic human renin substrate. Affinity chromatography of the pituitary renin on a Concanavalin-Sepharose column showed that most (87.4%) of the pituitary renin did not contain glycoprotein residues. Treatment with either trypsin or glandular kallikrein increased the renin activity, indicating the presence of an inactive form of renin in the pituitary tissue. From these findings, it is concluded that specific renin exists in human pituitary tissue. It seems likely that the pituitary renin is of local origin rather than contamination of the circulating enzyme.

Arterial renin, partial characterization and its possible role in the pathogenesis of hypertension

1) Renin-like enzyme of rat aorta was purified by chromatography with DEAE-cellulose and Sephadex G-200. 2) The molecular weight of renin-like enzyme was 124,000 and 72,000 on Sephadex G-200 gel filtration. The isozymes, however, migrated as a single band with molecular weight of 71,000 on SDS/polyacrylamide gel electrophoresis. These isozymes showed the same optimal pH (6.5) and temperature (37 degrees C). 3) Renin-like enzyme showed high activity in the microsomal fraction of the aorta. 4) In one-clip, two-kidney Goldblatt hypertensive rats, the aortic renin concentration increased significantly, but not parallel with the activity in plasma. 5) Renin, widely distributed in subcellular fractions of the aorta, may play a possible role in the local control of vascular tone. It is likely that renin in vascular wall is of local origin.