No abstract

We examined mRNA expression of the clock genes (Per1, Per2, and Bmal1) and PAI-1 (plasminogen activator inhibitor-1) after aldosterone treatment every 4 h up to 48 h in H9c2 cardiomyoblasts by reverse transcription-polymerase chain reaction. To block the MR (mineralocorticoid receptor), the MR antagonist, spironolactone, was added to the medium 1 h before aldosterone treatment. Aldosterone induced an initial increase and rhythmic expression of Per1, while spironolactone attenuated the acute increase in Per1 mRNA induced by aldosterone. On the other hand, aldosterone did not increase the Per2 mRNA in the acute phase, but thereafter induced a rhythmic expression of Per2. Aldosterone also induced rhythmic expression of Bmal1, a positive element of the clock genes. The rhythm of Bmal1 mRNA was anti-phase of that of Per2 mRNA. Aldosterone induced an acute increase in PAI-1 mRNA, but did not induce rhythmic expression of PAI-1. The present study demonstrated first that aldosterone regulates expression of the clock genes Per1, Per2, and Bmal1, and increases PAI-1 expression in H9c2 cardiomyoblasts. Second, an acute increase in Per1 mRNA after aldosterone treatment is mediated through MR. Third, clock genes are not related to PAI-1 expression in H9c2 cardiomyoblasts.

Hepatocyte growth factor (HGF) is a mesenchyme‐derived pleiotropic factor, and angiogenesis is included in a variety of its functional effects. HGF levels were measured in 5 sessions of low‐density lipoprotein (LDL) apheresis in 3 patients with severe hypercholesterolemia. Blood was collected at the start (T0) and at 1,000 ml (T1), 2,000 ml (T2), and 3,000 ml (T3) plasma treatments. During LDL apheresis, HGF levels increased from 1.59 ± 0.78 (mean ± SE, n = 5) ng/ml at T0 to 6.64 ± 0.97 at T1, 6.28 ± 0.97 at T2, and 5.20 ± 0.94 at T3. In one apheresis session, HGF increased immediately at the 100 ml plasma treatment stage. HGF was adsorbed completely by a dextran‐sulfate (DS) column. Despite the adsorption by the DS column, HGF in the patient blood increased to the levels with functional effects. The improvement of ischemic symptoms due to LDL apheresis may be related to the angiogenic activities of HGF.

The aim of this study was to assess the grade of heterogeneous disturbance in the renal cortical circulation using dynamic computed tomography and to investigate the relationship between the heterogeneity of renal cortical circulation and hypertension. We studied 125 patients who underwent dynamic computed tomography (CT) for various abdominal diseases and had no serious hemodynamic abnormalities. In dynamic computed tomography under appropriate conditions, each pixel (image element), less than 1 mm2, has a CT number that is in proportion to the concentration of contrast media, which reflects the blood volume in the pixel. The image was constructed at the hilus level about 50 s after the start of a continuous infusion of contrast medium. The mean and standard deviation were calculated from the CT numbers in the renal cortex. The coefficient of variation, ie, the standard deviation divided by the mean value, was used as the index of the heterogeneity of renal cortical circulation. The coefficient of variation was significantly (P < .001) greater in the hypertensive patients (n = 48, 0.174 +/- 0.006 [mean +/- SE]) than in normotensive subjects (n = 77, 0.140 +/- 0.004). The coefficient increased in parallel with the patient's age and with the grade of renal surface irregularity. In the patients whose serum creatinine levels were normal, this parameter also had a significant relationship (r = 0.367, P < .0001) with serum creatinine. These results suggest that the heterogeneity of renal cortical circulation is increased in hypertension and is also associated with aging. This parameter may become a sensitive indicator to detect slight deterioration in the renal cortical circulation.

The negative charges of dextran sulfate cellulose (DSC) used for low‐density lipoprotein (LDL) apheresis activate the intrinsic coagulation pathway, accompanied by bradykinin production. This study was undertaken to see whether an antagonist of angiotensin receptor (AT1), losartan, could be safely used in a patient treated by DSC‐LDL apheresis. Losartan (50 mg/day) was given to a patient with coronary heart disease who had been treated by DSC‐LDL apheresis and had experienced an anaphylactoid reaction by administration of an angiotensin converting enzyme inhibitor. The effects of losartan on blood pressures and humoral factors were examined by comparing these parameters between apheresis with and without losartan. Blood pressures and plasma levels of bradykinin, renin, and aldosterone were measured before and at 1,000, 2,000, and 3,000 ml of plasma treatment. Bradykinin levels during LDL apheresis tended to be higher with losartan than without losartan (without versus with, 529 ± 121 [n = 4, mean ± SE] pg/ml vs. 1,058 ± 49 at the 2,000 ml stage, p < 0.01). The rise of plasma renin activity with losartan (221 ± 26% at the 3,000 ml stage) was significantly greater than that without losartan (144 ± 2.4%). Mean blood pressure decreased by 7% during apheresis with losartan, but blood pressure reduction was not accompanied by any complaints. These results suggest that AT1 receptor antagonists are safely used in patients treated by DSC‐LDL apheresis.