Genetics of hypertensive diseases -- experimental studies on pathogenesis, detection of predisposition and prevention.
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Biomedical subjects
Publications and source records attributed to Y Nara.
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Erythrocyte membrane characteristics were examined in normotensive Wistar-Kyoto rats (WK), stroke-resistant spontaneously hypertensive rats (SHRSR) and stroke-prone SHR (SHRSP). The membrane of SHRSP was more labile against osmotic shock than that of SHRSR or WK at the age of 2 months. This membrane fragility was not dependent on their blood pressure. The membrane permeability of lipophilic ion, tetraphenylphosphonium, was increased in 1-month old SHRSP. These membrane characteristics in SHRSP were partially dependent on cholesterol amount which was significantly decreased in SHRSP. The method determining the membrane fragility was applied to human erythrocytes. Two groups of people were selected from about 2,000 inhabitants under our community health control program. The erythrocytes from the group with stroke in their family history were more labile than erythrocytes from the corresponding group without stroke in their family history. This result suggests that the examination of these membrane characteristics may give us a new method to detect a genetic risk to hypertension or stroke-proneness also in human.
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In order to investigate plasma bioactive PTH, we tried to assay the N-terminal portion of PTH by RIA. The antiserum to PTH was prepared by immunizing rabbits with a bovine 1-34 PTH conjugate BSA. A preparation of labeled PTH was radioiodinated by the chloramine-T or lactoperoxidase method. Labeled PTH was purified by means of adsorption by Quso G-32 powder or a sephadex G-50. The separation of the free and bound labeled hormone was performed by the dextran-coated charcoal method. The assay was carried out as follows: 0.2 ml diluted buffer (0.05 M, pH 8.6, veronal buffer), 0.1 ml standard PTH or sample to be tested, and 0.1 ml anti-PTH serum were mixed. After the first incubation at 4 degrees C for 4 days, 0.1 ml labeled PTH were added. After a second incubation at 4 degrees C for 12 hours, the assay tubes were centrifuged at 2,000 rpm for 30 min and the precipitates were counted. Various hypothalamic, pituitary and thyroid hormones did not interfere with the RIA for PTH. A dose response curve was obtained in a range from 100 pg to 5,000 pg per ml of standard PTH in this assay system. The serum immunoreactive PTH in healthy subjects values less than 290 pg per ml.
Studies of cardiac hypertrophy in spontaneously hypertensive rats have indicated that left ventricular hypertrophy occurred even in the prehypertensive stage. These findings suggested that other factors besides blood pressure levels, and including possibly a genetic predisposition to myocardial hypertrophy, could play a role in structural cardiovascular alterations in spontaneously hypertensive rats. More recent studies have confirmed these anatomic results; left ventricular hypertrophy was vectorcardiographically detected even in the prehypertensive stage in voth young stroke-prone rats and stroke-resistant spontaneously hypertensive rats. Further, a close relation was found between degree of left ventricular hypertrophy and vascular hypertrophy or hyperplasia; this suggests that early detection of left ventricular hypertrophy may be a useful indicator of the incipient stage of structural vascular changes in genetic hypertension.
1. The chemical characteristics of the vascular connective tissue components were determined in stroke-prone (SP), stroke-resistant (SR) spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WK) rats. 2. The ratio of hydroxylysine to hydroxylsine plus lysine in the vascular collagen was increased in 6-month-old SP-SH rats and SR-SH rats as compared with WK rats. 3. An age-related increase in uronic acid and hexose content of the aorta was noted in SP-SH, SR-SH and WK rats. However, the increase was more prominent in SH rats, especially SP-SH rats at the stages examined (11 weeks and over 8 months of age). 4. The ratio of galactosyl-hydroxylysine to glucosyl-galactosyl-hydroxylysine in the aortic collagen was decreased in 6-month-old SH rats, especially SP-SH rats as compared with WK rats. 5. A relative increase in beta and gamma components in aortic collagen was noted in 6-month-old SP-SH rats when compared with SR-SH rats. 6. The increased content of uronic acid and hexose and the structural changes of vascular collagen as demonstrated in SP-SH rats might be related to the fragility of the arterial wall and/or to the pathogenesis of stroke-proneness.
The level of plasma dopamine-beta-hydroxylase (DBH) activity in subjects at rest was found to be significantly lower in 12 patients on long-term hemodialysis than in a healthy 8-member control group: 28.3 +/- 7.2 and 13.6 +/- 7.6 IU/1, respectively (p less than 0.01). Following immersion of one hand of each subject into cold water (4 degrees C) for 1 min, a significant rise was observed in both groups, 6.1 +/- 4.8 IU/1 for the control and 1.6 +/- 1.4 IU/1 for the patient group (p less than 0.01). Upon tilting up the head of all subjects, activity in both groups increased significantly, but a markedly smaller rise was found in the patient group: 5.8 +/- 4.8 and 1.1 +/- 1.6 IU/1 for the two groups, respectively (p less than 0.01). The data suggest an autonomic nervous dysfunction in patients on long-term hemodialysis.
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