No abstract available.
Licensure*

It is still not well documented what the basic roles for the regulation of renin secretion from the kidney take place. Since the early study on the renal ischemia for the production of hypertension was introduced, the renin-angiotensin system has been regarded as the possible pathogenetic mechanism for the renovascular hypertension. The renin-angiotensin system, however, could be activated by various stimuli, such as, the changes of intrarenal perfusion pressure, the load or concentriation of sodium at the sites of macular densa, the changes of the sympathetic nervous activity and the changes of potassium balance. To investigate the renin-angiotensin system and the influence of sympathetic nervous system on the regulation of renin secretion, the renovascular hypertension was induced in the dogs by constriction of unilateral renal artery, and the plasma renin activity was measured. The sodium load at the sites of macula densa was attained by furosemide, and then the activity of sympathetic nervous system was depressed by reserpine. The plasma renin activity was assayed by the method of Helmer and Cohn. By this bio-assay method, the plasma renin activity equivalent to 1 nanogram angiotensin-II can be measurable and the prepared plasma was found to have still vasopressor activity. The results observed in this experimental work are summarized as follows. 1. The blood pressure reached maximum on the 3rd postoperative day, and declined gradually to the level of preoperative day on the day of from the 6th to 12th day following constriction of renal artery. 3. The plasma renin activity was found to be well correlated with the increase of blood pressure, and then declined to its preoperative level with the reduction of blood pressure. It appears, therefore, that the renin-angiotensin system plays an important role in the pathogenesis of renovascular hypertension. 4. The urine flow rate in normal and reserpinized dogs was the same before administration of furosemide, but its rate was significantly increased in both groups after furosemide. The urine flow rate of reserpinized dogs, however, was significantly lower than that of the normal dogs during the first 5 minutes. 5. The urinary sodium excretion in normal and reserpinized dogs was significantly increased in both groups after administration of furosemide and there were no difference between the two groups. 6. The plasma renin activity of renal venous blood was significantly higher than that of femoral arterial blood in both groups before and after administration of furosemide. 7. The plasma renin activity of reserpinized dogs was significantly lower than that of normal dogs before administration of furosemide. After furosemide, however, the plasma renin activity was significantly increased in 30 minutes in both groups. This increase of plasma renin activity was less prominent in resepinized dogs than in normal. This results would suggest that the intrarenal mechanism regulating renin secretion also requires an intact sympathetic nervous system.
Animals ; Blood Pressure ; Constriction ; Dogs ; Furosemide ; Hypertension ; Hypertension, Renovascular ; Ischemia ; Kidney ; Perfusion ; Plasma ; Potassium ; Renal Artery ; Renin* ; Renin-Angiotensin System ; Reserpine ; Sodium ; Sympathetic Nervous System

No abstract available.
Breast Neoplasms* ; Breast*

No abstract available.
Extracorporeal Membrane Oxygenation*

Cyclosporine A (CSA), a lipophilic cyclic undecapeptide, is not accumulated evently in all tissues and has a high affinity to several tissues such as lymphoid organs, liver, and kidneys. From this point of view, it is reasonable to assume that the amount of CSA uptake would be correlated with the extent of cell injury. On the other hand, verapamil, a Ca2+ channel blocker, bas been shown to ameliorate CSA nephrotoxicity. Since proximal tubule is the major site of drug transport and CSA uptake and its interaction with verapamil in isolated human renal proximal tubular cells. The CSA uptake rapidly increased over the first 5 min and then achieved almost steady-state after 10 min at all concentrations (0.5-10 uM). Kinetic analysis yielded that the Km and Vmax values of CSA were 5.6 uM and 86.2 p mol/mg cell protein/min, respectively. And Ca2+ depletion in media enhanced CSA uptake significantly but verapamil reduced it. These results suggest that the Ca2+ channels and CSA transporting sites on cell membrane are closely associated and that Ca2+ and CSA might be taken up competitively by proximal tubular cells.
Humans

Nephrotoxicity is the most common dose-limiting factor of cyclosporine A (CSA) in clinical usage. But the mechanism of CSA-induced nephrotoxicity still remains unresolved. Many authors insisted that CSA induced renal proximal tubular cell injury is due to the secondary effects following hemodynamic changes or endothelial cell damage, instead of direct toxicity by CSA. To find out that CSA has a direct toxicity to the proximal tubular cells, the author used primary cultures of human proximal tubular cells to eliminate the hemodynamic or endothelial influences that could be produced in in vivo model. In the present study, the viability against CSA was tested by the neutral red assay method with modulation of Ca2+ amount in incubating media and observed electron microscopically. The viability test showed direct toxic effect of CSA on human proximal tubular cells and this was enhanced by Ca2+ depletion in incubating media. Morphologically noted are accumulation of lipid droplets and polyribosomal dispersion, which may be association with inhibition of cellular synthetic activity. These results suggest the toxixity is a direct effect of cyclosporine and that toxic mechanism may be due to inhibition of cellular synthetic activity. And this experiment also showed that primary cultures of human renal proximal tubular cells can be a good in in vivo model for investigating CSA nephrotoxicity.
Humans

No abstract available.

No abstract available.
Allografts* ; Skin* ; Tuberculosis*

No abstract available.
Drug Therapy*

No abstract available.
Apoptosis* ; Pulmonary Disease, Chronic Obstructive*