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Biomedical subjects

M Nagano

Publications and source records attributed to M Nagano.

At least 253 records · Page 14Linked to original sources

Extrarenal role of aldosterone in the regulation of blood pressure.

To assess the hypothesis that aldosterone may have direct vasoconstrictive action, the acute effects of canrenoate potassium (Soldactone, S), an aldosterone antagonist, on hemodynamics and hormonal responses were determined before and after the intravenous administration of 2 mg/kg S in 11 patients with primary aldosteronism (PA), 9 patients with essential hypertension (EH), and 5 patients with renovascular hypertension (RVH). S caused a significant -12 +/- 2 mm Hg decrease in MBP in PA, -5 +/- 2 mm Hg in EH, and -4 +/- 1 mm Hg in RVH. Reduction in MBP was significantly higher in PA than in the others and there was a negative correlation between changes in MBP and basal PAC. The cardiac index did not change throughout the study in all groups, which led to a significant reduction in total peripheral resistance index (TPRI) in PA but not in the others. There was a significant correlation between changes in MBP and TPRI (r = 0.82, p less than 0.01). PRA did not change throughout the study, but PAC and cortisol were significantly elevated. There were no correlations between changes in MBP and hormonal responses. In conclusion, S resulted in a significant reduction of MBP mediated by a significant reduction of TPRI. These results suggest that aldosterone may have direct vasoconstrictive action and this extrarenal effect of aldosterone may be involved in the regulation of blood pressure.

Adult↗

Impaired aldosterone production by chronic intravenous infusion of atrial natriuretic factor in rabbits.

This study assessed the effect of chronic infusions of atrial natriuretic factor (ANF) on in vivo and in vitro production of aldosterone. Male New Zealand white rabbits were intravenously infused for 5 days with either vehicle (0.9% NaCl solution) or rat ANF (99-126) at 100 ng/kg per h. In ANF-infused rabbits plasma ANF levels increased 2.7-fold, plasma renin activity (PRA) was reduced and plasma aldosterone, but not blood pressure, responses to exogenous angiotensin II (Ang II) were attenuated. In adrenal capsular cells isolated from rabbits chronically infused with ANF, maximal aldosterone responses to adrenocorticotrophic hormone, Ang II and potassium were significantly reduced without any changes in sensitivity. These results suggest that chronic small increases in circulating ANF can blunt aldosterone responses to various aldosterone secretogogues without inhibiting the pressure response to Ang II.

Adrenal Glands↗

Immunoreactive prorenin and its profragment peptide are present in human juxtaglomerular cells.

Although prorenin appears to be activated through the cleavage of its prosegment in the juxtaglomerular cells, the presence of prosegment peptide has never been demonstrated. We therefore studied prorenin in juxtaglomerular tumour cells, both by immunohistochemistry and by radio-immunoassay. Synthetic peptide covering the 14-carboxyterminal sequence of human renin prosegment was used to prepare both antibody and radiolabelled tracer. Intense immunostaining of prorenin was demonstrated in the tumour cells. By gel filtration, however, immunoreactive prorenin was shown to consist of two major components. The first peak, located at the elution position of activatable inactive renin, was regarded as prorenin. The other peak was located at an elution position with a smaller molecular weight, which was assumed to represent the profragment. These results suggest that both prosegment peptide and prorenin are present in the juxtaglomerular cells.

Adult↗

Acid-base changes in ischemic myocardium and intervention with hypothermia or bicarbonate.

Effects of ischemia and reperfusion on acid-base changes in relation to myocardial contractility, and the effects of correcting H+ were studied by lowering PCO2 or increasing HCO3- levels. The hearts were perfused by working heart mode and whole heart ischemia was induced by use of a one way valve followed by myocardial warming (37 degrees C, normothermia), cooling (18 degrees C, hypothermia) or warming plus 2.1 mM NaHCO3 for 15 min. The hearts were then reperfused for 20 min. Coronary effluent was collected through pulmonary artery cannulation and used for the measurement of acid-base changes. There were close correlations between the decrease in coronary flow and LV pressure, LV dP/dt. Close correlations were also observed between the decline in LV pressure and the rise in PCO2, H+, and the decline in HCO3-. A highly significant correlation was seen between H+ and lactate production. Myocardial contractility decreased to the same extent in 3 groups during ischemia, whereas its recovery rate in both the hypothermia and HCO3- -treated groups were significantly higher than in the normothermia group. The increment of H+ was significantly less in both the hypothermia and HCO3- -treated groups than in normothermia. These results indicate that lactate production is the major H+ producing source and the correction of H+ could minimize the ischemic insult and at the same time contribute to the reperfusion injury.

Acid-Base Imbalance↗

Myocardial mechanical and myosin isoenzyme alterations in streptozotocin-diabetic rats.

Fifteen week old male Wistar rats (n = 7) were made diabetic by intravenous injection of streptozotocin (50 mg/kg). Age-matched, untreated male Wistar rats (n = 9) served as controls. Hearts were removed after 5-6 weeks of diabetes, and the isometric developed tension (T) of isolated left ventricular papillary muscles and its first derivative (dT/dt) were measured at a frequency of 0.2 Hz. During testing, the muscles were perfused with Tyrode's solution (Ca2+ concentration was half of normal Tyrode's solution, pH 7.4, 32 degrees C, bubbled with 95% O2 and 5% CO2). In addition, the left ventricular isoenzyme pattern, which is related to myocardial energetics, was determined by pyrophosphate gel electrophoresis. There was no significant difference in isometric developed tension between diabetic and control rats (DM: 2.90 +/- 0.89 vs controls: 2.87 +/- 0.85 g/mm2, mean +/- SD), but in diabetic rats, dT/dtmax decreased significantly as compared with controls (DM: 23.5 +/- 4.2 vs controls: 31.9 +/- 7.9 g/mm2.s, p less than 0.05). Myocardial mechanical responses to isoproterenol (10(-7)M) and dibutyryl cyclic AMP (10(-5)M) also decreased in diabetic rats. The left ventricular myosin isoenzyme pattern shifted toward VM-3 in diabetic rats (VM-3: DM: 74.9 +/- 10.7 vs controls: 9.5 +/- 4.1%, p less than 0.001). These results indicate that diabetes influences myocardial contractility and changes cardiac energetics. Post-receptor processes may play a role in myocardial mechanical responses to catecholamines in streptozotocin-diabetic rats.

Animals↗

Effects of bunitrolol on myocardial contractility and left ventricular myosin isoenzyme pattern.

Effects of long term treatment of hypertension with bunitrolol on myocardial contractility and left ventricular myosin isoenzyme pattern were examined. Male 22-week-old spontaneously hypertensive rats were treated with bunitrolol (30-40 mg/kg/d, p.o.) for 8-10 weeks. The blood pressure of the bunitrolol-treated group did not differ from that of the untreated group, but ratio of ventricular weight to body weight was significantly lower in the treated group. There were no significant differences in isometric developed tension and dT/dtmax of isolated left ventricular papillary muscles between bunitrolol-treated and control groups. Myocardial mechanical responses to isoprenaline (isoproterenol) also showed no differences between the two groups. Left ventricular myosin isoenzyme pattern obtained by pyrophosphate gel electrophoresis was significantly shifted to VM-1 by bunitrolol treatment.

Animals↗

Visualization of secretory activities in the Xenopus neurohypophysis by a high S/N video camera.

The optical turbidity of neurohypophyses of the frog Xenopus laevis was observed with the help of a high signal to noise ratio video camera and a high speed image processor. Electrical stimulation of the pituitary stalk induced a decrease in turbidity of the neurohypophysis. This response was visualized on a monitor screen as a diffuse pattern consisting of many bright spots. The diameters of these spots were similar to those of individual nerve terminals, indicating that the optical response arises from a structural change in individual nerve terminals upon secretory activation.

Animals↗

Lipoprotein lipase activity in ischaemic and anoxic myocardium.

Myocardial lipoprotein lipase (LPL) activity during ischaemia has not been fully understood, although it plays an important role in regulating myocardial fatty acid metabolism. In this experiment, the effects of ischaemia (Experiment A) and anoxia (Experiment B) on two distinct fractions of LPL, i.e. functional and nonfunctional forms were investigated in isolated, perfused rat heart. In Experiment A, hearts were perfused by Neely-Morgan working heart mode with Krebs Henseleit bicarbonate (KHB) buffer (95% O2:5% CO2), then whole heart ischaemia was induced by using a one-way aortic valve, simultaneously switching to the same buffer but containing heparin (5 mu/ml) for 20 min. In Experiment B, the hearts were perfused by Langendorff method with KHB buffer (95% O2:5% CO2) and the buffer was switched to KHB (95% N2:5% CO2) containing heparin for 20 min. Coronary effluent was collected at 5 min intervals and used for the measurement of functional LPL activities using 3H-glyceryltrioleate. The hearts were quickly frozen at the end of perfusion and homogenized. The suspension was used for the measurement of non-functional LPL activities. In Experiment A, functional LPL activities in ischaemia were significantly lower than in the aerobic condition. On the contrary, the nonfunctional LPL activity in ischaemia was significantly higher than in the aerobic condition. In Experiment B these values were also significantly lower than in the aerobic condition. However, there was no significant difference in non-functional LPL activity between the anoxia and aerobic condition. These results indicate that there is a conversion defect from the precursor of LPL to the functional form of LPL in ischaemia, whereas disturbed LPL synthesis might be involved in anoxic myocardium.

Animals↗

Myocardial contractility and left ventricular myosin isoenzyme pattern in cardiac hypertrophy due to chronic volume overload.

Chronic volume overloaded cardiac hypertrophy was induced by abdominal arteriovenous shunt in 10-week-old male Wistar rats. Ten weeks after the operation, myocardial mechanical examination was performed with isolated left ventricular papillary muscles. Left ventricular myosin isoenzyme pattern was also examined by pyrophosphate gel electrophoresis. In addition, morphological study by electron microscope was performed. In arteriovenous shunt rats, isometric developed tension (T) and its first derivative (dT/dt) were decreased, resting tension (RT) was increased and time to peak tension (TPT) was prolonged as compared to sham-operated control rats (T: 2.4 +/- 0.5 vs 2.8 +/- 0.8 g/mm2, NS. dT/dt: 23.9 +/- 4.8 vs 31.9 +/- 7.0 g/mm2.s, p less than 0.05. RT: 1.2 +/- 0.2 vs 0.9 +/- 0.1 g/mm2, p less than 0.05. TPT: 151.7 +/- 20.2 vs 128.3 +/- 10.3 msec, p less than 0.05). Myocardial mechanical responses to isoproterenol (10(-7) mol/l) and dibutyryl cyclic AMP (10(-5) mol/l) were both depressed in hypertrophied myocardium, although not significant statistically. Left ventricular myosin isoenzyme pattern was shifted towards VM-3 by chronic volume overload. Electron microscope study revealed increased collagen content in hypertrophied myocardium.

Adenosine Triphosphatases↗