The effects of administration of angiotensin II (ANG II) and antidiuretic hormone (ADH) on the glomerular filtration rate (GFR, measured as creatinine clearance) were examined in patients with mesangial proliferation. For this study, the patients whose conditions were similar to that of healthy subjects, except for asymptomatic urinary abnormalities and glomerular histological changes, were selected. Both ANG II and ADH administration significantly decreased GFR in the patients and the healthy subjects. Compared to the healthy subjects, a significantly greater drop in GFR was observed in the patients following ANG II infusion with or without SQ14225 administration, but not following ADH infusion. We conclude that mesangial proliferation may modulate an ANG II induced drop in GFR.

View full abstract

In order to examine the effect of treatment of mild hypertension of the aged, a 4 year prospective trial was performed in 41 placebo and 38 drug-treated patients with an average age of 76.5 years. Patients were matched for blood pressure, sex and age. Patients with cardiovascular complications or blood pressure elevation above 200/110 were categorized as dropouts and totaled 17 cases (41.5%) in the placebo group, and 4 cased (10.5%) in the drug-treated group (p < 0.01). In diastolic hypertension, dropouts formed 63.6% of the placebo group (mean BP, 170/92), and 9.5% of the drug group (mean BP, 179/94) (p < 0.001). In systolic hypertension, dropouts were of 15.8% in the placebo group (mean BP, 164/79), and of 11.8% in the drug group placebo group, dropouts were significantly higher in patients with pretreatment systolic blood pressure over 170 mmHg or diastolic blood pressure over 90 mmHg. In patients of 75 years of age or more, dropouts were 46.4% in the placebo group, and 13.0% in the drug treated group showing the beneficial effect of drug treatment even in those over the age of 75. However, no beneficial effect was observed over the age of 85. Stepwise multiple regression analysis of total case revealed that the greatest predictor for dropout was the presence of placebo (i.e. no treatment), explaining 12.2% of the variation in future dropout. Similarly, diastolic hypertension explained 7.5%, creatinine 6.7%, and age 4.6% of this variation. In the placebo group, the greatest strength of prediction for dropout was diastolic hypertension, explaining 23.5%, followed by creatinine 6.1%, systolic blood pressure 6.1%, and obesity 5.1%. This study indicates the importance of drug treatment in the elderly hypertension by early eighties, when blood pressure exceeds 170/90 mmHg.

View full abstract

We studied the effects of a potassium supplement on urinary kallikrein excretion in a setting of high sodium intake after sodium deprivation with diuretics in young patients with borderline hypertension. Eleven patients, who took the potassium supplementation during the high sodium diet period, showed lower increments in mean blood pressure with salt loading than 12 patients without the potassium supplementation. In the non-potassium-supplemented patients, urinary kallikrein was increased significantly when plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary aldosterone were increased during the diuretic treatment. It was decreased significantly when the other hormones were decreased during the sodium load. During the high sodium diet period, PRA, PAC and urinary aldosterone were greater in the potassium-supplemented patients than in the non-potassium-supplemented ones, but urinary kallikrein excretion was not higher when potassium was supplemented. Thus, the present results did not support the theory that the kallikrein-kinin system may be involved in the natriuretic and antihypertensive effects of potassium. In addition, these finding suggest that some kallikrein-modulating factor(s) may counteract the increased urinary kallikrein excretion with the augumented renin-angiotensin-aldosterone system during salt loading with potassium supplementation.

View full abstract

Vectorcardiograms (VCG) were recorded from five spontaneously hypertensive rats (SHR) and five age-matched normal wistar rats (WR). Arterial systolic blood pressure was 115 ± 10.8 mmHg in WR and 176 ± 7.7 mmHg in SHR. The basic procedures for recording VCG in the rat were investigated. After rats were anesthetized with urethane-chloralose, VCG were taken by using the McFee-Parungao lead system in restrained ventral position. VCG in SHR were characterized by superior, posterior and leftward shift of QRS loops, a more elliptical form of QRS loops in the horizontal plane, and an increase in QRS-T angles in all planes, when compared with WR. These vectorcardiographic findings in SHR were quite similar to those produced by left ventricular hypertrophy in humans.

View full abstract

The accumulation of intermediates subsequent to impaired β-oxidation of free fatty acid (FFA) has been suggested as a cause of cellular damage in ischemic myocardium. ^1-2 We investigated the effects of propranolol and diltiazem on carnitine metabolism in ischemic myocardium. Propranolol (0.2 mg/kg/min, i.v.) and diltiazem (0.1 mg/kg/min, i.v.) were administered for 5 min, the administration started 10 min before coronary occlusion. ECGs were continuously recorded throughout the experiment. Myocardial samples were prepared from both the non-ischemic and ischemic areas 40 min after coronary ligation. Adenosine triphosphate (ATP), free carnitine, long chain acyl carnitine and long chain acyl CoA were assayed. Propranolol reduced the decrease of ATP and the accumulation of long chain acyl CoA, induced by myocardial ischemia. Diltiazem reduced the decrease of ATP and free carnitine, and the accumulation of long chain acyl carnitine in the ischemic area. Propranolol and diltiazem significantly reduced the grade of ventricular arrhythmia. These results suggest that the protective mechanisms of propranolol and diltiazem on myocardium are based, at least in part, on their beneficial effects upon myocardial carnitine metabolism

View full abstract

The authors recently reported the development of a new method for measuring angiotensin converting enzyme (ACE) by means of highly sensitive angiotensin II RIA technique. We have carried out a comparative study of the pharmacological properties of captopril and MK-422, two ACE inhibitors recently developed as new antihypertensive agents. In this study, in vivo and in vitro animal experiments were performed using the Gottingen Mini-pig (Mini-pig G) animal model of the human disease. In the in vivo experimental system, each drug was administered by intravenous injection at a dose of 1 mg/kg, and a slight difference was found in the time-course of the per cent inhibition of ACE in the blood. In the in vitro system (cultured aortic endothelial cells), the ACE inhibitory activities of the two drugs were compared in terms of the 50%-inhibition point on the dose response curve, and it was found that MK-422 was about 100 times more potent than captopril. These results indicate that our newly-developed experimental system can be useful in the establishment of the clinical dose of vasoactive drugs that act on the renin-angiotensin system.

View full abstract

The effects of taurine on central cardiovascular regulation were investigated by intracerebroventricular (ICV) injection of taurine in urethane-anesthetized rats. Blood pressure fell gradually to attain the maximum level at 10 to 15 min after the injection of 50 μg taurine and returned to the basal level 20 min later. After injecting 200 μg of taurine, blood pressure began to fall within 30 secouds and attained the maximum level at 2 to 5 min and did not return to the basal level by 20 min. Both heart rate and abdominal sympathetic nerve activity decreased as the blood pressure fell, However, the similar amount of taurine injected intravenously did not affect the blood pressure, the heart rate or the abdominal sympathetic nerve activity. These results suggest that taurine causes the central nervous system to lower the blood pressure by decreasing the sympathetic nerve outflow.

View full abstract

Studies were conducted in anesthetized dogs to examine the influence of the renal sympathetic nerves on renal hemodynamic and renin responses during controlled hypercapnia. The dogs were subjected to unilateral denervation and tested for their responses to hypercapnia induced by inhalation of 15% CO₂ in air. Simultaneous measurements of the responses from both the denervated and innervated kidneys allowed an assessment of the influence of the renal nerves on the responses during acute hypercapnia. The data indicate that reductions in renal blood flow and glomerular filtration rate and increases in renin of the renal vein during respiratory acidosis are dependent, in part, on the presence of intact renal nerves. Other factors, however, are probably also present.

View full abstract

The role of phospholipids in the maintenance of β-adrenoceptor function was investigated in isolated canine myocytes prepared from eight adult mongrel dogs by using collagenase. The characteristics of β-adrenoceptors were assessed by determining the number and the affinity of receptors by a radio-active ligand binding assay using ¹²⁵I-iodocyanopindolol. The increase in cyclic AMP content induced by isoproterenol or forskolin was also determined by radioimmunoassay with or without pretreatment with phospholipase (PLase) A₂. The amount of free fatty acids released from isolated myocytes by PLase A₂ was measured by high-performance liquid chromatography. PLase induced a significant decrease in the number of β-adrenoceptors but did not affect their affinity. Although the isoproterenol-stimulated increase in cyclic AMP was significantly inhibited by the pretreatment with PLase A₂, the forskolin-stimulated increase as not affected. Responsive accumulation of cyclic AMP to isoproterenol was much more impaired than the decrease in β-adrenoceptor number. These results indicate that PLase A₂ deteriorates the function of the adenylate cyclase system linked-β-adrenoceptor, and suggest that PLase A₂ affects both β-adrenoceptors and the coupling of β-adrenoceptors with adenylate cyclase.

View full abstract

The effect of intravenous administration of urokinase on the rate and time of thrombolysis was investigated in 22 dogs with an occlusive coronary artery thrombus induced by placement of a copper coil in the left anterior descending artery. One hour after angiographic confirmation of complete coronary artery occlusion, an intravenous bolus of urokinase was administrated in a dose of either 1.2×10⁶ units (Group 1, n=7); 0.6×10⁶ units (Group 2, n=9) or 0.3×10⁶ units (Group 3, n=6). Reperfusion occurred in all 7 (100%) Group 1 dogs, in 7 of 9 (78%) group 2 dogs and in 3 of 6 (50%) group 3 dogs (p=0.07 for Group 1 vs Group 3). There was no residual intra-arterial thrombus in any group 1 (high dose) dog but 4 of the 10 reperfused Group 2 or Group 3 (intermediate or low dose) dogs had small thrombus in the distal left anterior descending artery (3.5±4.0 mg) and all 5 non-reperfused dogs had thrombus in the coil (26.1±6.2 mg). The frequency of residual thrombus was significantly less in Group 1 compared to Group 2 and 3 (P < 0.01). We conclude that intravenous administration of urokinase has a dose dependent efficacy for lysing intracoronary thrombus in the canine model.

View full abstract

As a result of mass-screening, a 7-year-old girl was noted to have an abnormal shadow and was subsequently diagnosed as having a pericardial cyst. During surgery, we discovered that the cyst originated from the epicardium, and only its free wall was resected with the cyst left open to the pericardial cavity. The postoperative course was uneventful. This is presumed to be the first case of epicardial cyst ever reported in Japan. In diagnosing the epicardial cyst, the use of chest films, echocardiography and computed tomography assist angiography in making a differencial diagnosis from intracardiac lesion. In treatment, surgical resection is advised. Even though the cyst may be asymptomatic, the possible compression on the surrounding organs and possible rupture into the pericardial cavity must be avoided.

View full abstract