Masaru Minami

Lipid alterations in renal membrane of stoke-prone spontaneously hypertensive rats.

Phospholipase A2 activity, pbospholipids, and phospholipid fatty acids were investigated in renal membrane of male stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto rats. Renal phospholipase A2 activity increased and membranous phospholipids, especially phosphatidylchoUne and phosphatidylethanolamine, decreased with age in SHRSP. Arachidonate in phospholipid also decreased with age in SHRSP. To determine the effect of pressure load on the lipid alterations in renal membrane, SHRSP that received antihypertensive treatment with hydralazine, enalapril, or nicardipine for 5 weeks were compared with those without treatment. Antihypertensive treatments prevented phospholipid degradation and increased arachidonate in phospholipid relative to the control group. Phospholipase A2 activity in each group treated with antihypertensive drugs did not differ from that in the control group. These results suggest that the course of hypertension causes renal membranous phospholipid degradation and increases phospholipase A2 activity. Antihypertensive treatments may prevent these lipid alterations in SHRSP. These renal membranous structural changes may provide an explanation not only for functional abnormalities such as decreased membrane fluidity but also for the progress of hypertension.

Effect of furosemide in congestive heart failure

The diuretic effect of furosemide was studied in 18 patients with congestive heart failure. Subjects were divided into two groups, group I consisting of eight patients with moderate and group II of 10 patients with advanced congestive heart failure. Six hours after bolus injection of furosemide (40 mg), mean urinary sodium was 120.5 ± 36.7 mEq in group I and 68.2 ± 25.8 mEq in group II (p < 0.01), mean urine volume was 1,100 ± 281 and 764 ± 257 ml (p < 0.05), mean urinary furosemide excretion was 28.08 ± 2.60 and 24.00 ± 0.74 mg (p < 0.05), and mean furosemide renal clearance was 73.4 ± 16.6 and 42.3 ± 11.5 ml/min (p < 0.001). Diuretic effect and furosemide renal clearance, as well as urinary furosemide excretion, correlated positively. The diuretic effect of furosemide with and without hydralazine (0.2 mg/kg) was compared in eight patients in group II. Urinary sodium excretion 6 hr after furosemide rose from 77.2 ± 31.0 to 122.8 ± 42.5 mEq after furosemide with hydrlazine (p < 0.01). Urine volume rose from 854 ± 278 to 1,279 ± 359 ml (p < 0.001), urinary furosemide excretion rose from 23.64 ± 2.03 to 26.94 ± 2.30 mg (p < 0.01), and furosemide renal clearance rose from 46.3 ± 12.2 to 62.5 ± 18.6 ml/min (p <0.01).

Effect of coenzyme Q10 on structural alterations in the renal membrane of stroke-prone spontaneously hypertensive rats

To test the hypothesis that structural abnormalities exist in the kidney membrane of spontaneously hypertensive rats, we examined the effect of long-term administration of coenzyme Q10 on membrane lipid alterations in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP). As compared with normotensive Wistar-Kyoto rats, renal membrane phospholipids, especially phosphatidylcholine and phosphatidylethanolamine, decreased and renal phospholipase A2 activity was enhanced with age in untreated SHRSP. Treatment with coenzyme Q10 attenuated the elevation of blood pressure, the membranous phospholipid degradation, and the enhanced phospholipase A2 activity. These results suggest that one factor contributing to the progress of hypertension is a structural membrane abnormality that alters the physical and functional properties of the cell membrane, and coenzyme Q10 might protect the renal membrane from damage due to hypertension in SHRSP.

Effects of clonidine and guanfacine on drinking and ambulation in spontaneously hypertensive rats

Present experiment was undertaken to compare the effects of clonidine and guanfacine on water drinking behavior and ambulatory activity in spontaneously hypertensive rats (SHR). Equipotent hypotensive doses of clonidine and guanfacine, 150 micrograms/kg and 1500 micrograms/kg, respectively, given twice a day at 8:00 and 20:00, produced a triphasic pattern of behavioral changes; initial increase in water drinking and ambulation during the light period, decrease in water intake and ambulation at the beginning of the dark period, and a second increase in water drinking and ambulation at the end of the dark period. Guanfacine treated SHR showed less change in water drinking behavior and ambulation than the clonidine treated SHR.

Behavioral and Neurochemical Evaluation of Stroke-Prone Spontaneously Hypertensive Rats for Vascular Dementia-Animal Model

The stroke-prone spontaneously hypertensive rat (SHRSP) is known to be an unique model of stroke because the lethal time course of SHRSP coincides well with that of patients with cerebrovascular lesions (Okamoto et al., 1974). The aim of the present study was to clarify the proposed possibility that. SHRSP may be a vascular dementia-animal model. First, a study was carried out to evaluate stroke-related behavioral changes and learning ability using passive avoidance response. An attempt was also made to investigate the pathophysiology of SHRSP as an animal model for cerebrovascular lesions by determining neurotransmitter levels in cerebrospinal fluid (CSF).

Relationship between lipids and angiographically defined coronary artery disease in Japanese patients

The relationship between the severity and extent of coronary artery disease (CAD) and the lipid profiles was evaluated in 120 Japanese male patients, who underwent coronary angiography. Analysis of the lipid quartile distribution showed that the percentage of patients with significant CAD increased as the total cholesterol (TC) increased and high-density lipoprotein cholesterol (HDL-C) decreased. In addition, as the number of vessels with marked coronary artery stenosis increased, TC and TC/HDL-C increased while HDL-C decreased. However, within this population, triglyceride level, high blood pressure, and smoking were not significantly associated with coronary angiographic findings.

Positive inotropic and negative chronotropic effect of pantethine on isolated cardiac muscle of guinea-pigs

It was demonstrated that pantethine, a component of co-enzyme A, produces positive inotropic and negative chronotropic actions in isolated cardiac muscle preparations from guinea-pigs.

Cardiovascular Effects of SK&F 64139, a PNMT Inhibitor, in Rats

PNMT catalyzes NE to Ep in the final steps of catecholamine synthesis. Pendleton et al. (1980) have reported that SK&F 64139 (SKF) is a potent and reversible inhibitor of PNMT (1). Because of the ability of SKF to cross the blood brain barrier (1), this compound lowers Ep levels both in the adrenal gland and in the CNS. The BP lowering effect of SKF was accompanied with a marked decrease in central PNMT activity. This further supports the interpretation that this is its main hypotensive mechanism (2). The present study was undertaken to elucidate the effects of SKF on BP, HR and adrenal catecholamine contents in rats. In order to elucidate the mechanism of cardiovascular effects induced by SKF, ICNA was also determined.

Dopamine Sulfate and the Cardiovascular System

Approximately 80% of the total NE and Ep and 90% of the total DA in circulation consists of conjugated catecholamines (1–3). Kuchel et al (4) reported that increased plasma concentrations of DA-S were observed in patients with essential hypertension. In a recent study (5), we found that the levels of DA-S in the plasma of patients with CHF were 3-fold higher than control values. We also reported that DA-4-S has a positive inotropic effect on isolated rabbit papillary muscles (6). However, the source and physiological role of the sulfate catecholamines remain unknown. In order to investigate the site and the mechanism of action of DA-S, we have synthesized DA-4-S and DA-3-S (Fig.l). The present study was undertaken to determine the affinity for the receptor related to the positive inotropic effect. An attempt was also made to determine the role of sulfate in the conversion of DA-S into free DA and cAMP in various tissues of the rabbit.