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Biochem Int. 1991 Jan;23(2):419-28.
Hepatic and renal metallothionein induction in the rat and mouse after treatment with furosemide.

Wormser U, BenZakine S, Nyska A.

Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Induction of hepatic and and renal metallothionein by furosemide was studied in the rat and mouse. Treatment of mice with 200 and 300 mg/kg furosemide elevated hepatic metallothionein by 117% and 366%, while renal metallothionein was induced by 29% and 380%, respectively. In the rat the drug was less potent i.e. liver metallothionein was increased by 167% and 217% following injection of 300 and 400 mg/kg furosemide, respectively, whereas kidney was not significantly changed by this treatment. The mouse hepatic and renal metallothionein was identified as zinc-containing thionein by Sephadex G-75 gel filtration (Ve/Vo = 2.0). In both species maximal induction was observed 24 hours post exposure. However, the mouse hepatic and renal metallothionein content declined after additional 24 hours whereas the rat metalloprotein was not reduced even after 72 hours of treatment. It is suggested that alterations in metal homeostasis may be responsible for hepatic and renal metallothionein induction caused by furosemide.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1859441&dopt=Abstract




J Clin Hypertens. 1987 Dec;3(4):681-4.
The role of plasma angiotensin I converting enzyme in regulation of renin-angiotensin system activity in patients with essential hypertension.

Ishida H, Shimamoto K, Ando T, Nishitani T, Hosoda S, Yokoyama T, Fukuyama S, Mori Y, Nakagawa H, Ogata H, et al.

Second Department of Internal Medicine, Sapporo Medical College, Japan.

In order to investigate the role of plasma angiotensin I (pAI) converting enzyme on the activity of the renin-angiotensin system, we measured plasma renin activity (PRA), plasma angiotensin II (pAII), and plasma angiotensin I converting enzyme (pACE) activity in fourteen patients with essential hypertension before and after two hours of ambulation combined with intravenous furosemide administration. Significant increases were observed in the values of PRA (p less than 0.005), pAII (p less than 0.005) and ACE activity (p less than 0.05) after ambulation. The ratios of log pAII/log PRA were increased significantly after ambulation (p less than 0.005), and a significantly positive correlation was observed between log pAII/log PRA and ACE activity (p less than 0.01). These results suggested that not only PRA but also ACE activity contributed to the activity of renin-angiotensin system through the generation of AII.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2839630&dopt=Abstract




J Clin Endocrinol Metab. 1993 Oct;77(4):1020-7.
Reduced response to metoclopramide and anomalous rising response to upright posture of plasma aldosterone concentration in Japanese patients with aldosterone-producing adenoma.

Mune T, Morita H, Yasuda K, Yamakita N, Miura K.

Third Department of Internal Medicine, Gifu University School of Medicine, Japan.

We examined the changes in plasma aldosterone concentration (PAC) during 3 kinds of postural stimulation tests and a metoclopramide test in 20 Japanese patients with surgically proven aldosterone-producing adenoma. In the 2-h upright test (n = 16), PAC increased (P < 0.01) in 14 of 16 patients, with a mean percent change of 135 +/- 42% (+/- SD) of the supine levels without any significant change in plasma cortisol. In the furosemide-upright test (n = 17), PAC increased (P < 0.01) in 15 of 17 patients by 131 +/- 27%, with a significant increase in cortisol. However, in the furosemide upright test after dexamethasone pretreatment, which suppressed plasma cortisol during the test, PAC also increased (P < 0.01) in all 9 patients examined by 158 +/- 36%. Angiotensin-II infusion failed to increase PAC in all 4 patients examined whose PAC increased with postural stimulation tests. Injection of 10 mg metoclopramide (n = 13) induced a significant, but less marked, increase (P < 0.01) in PAC to 157 +/- 59% of basal levels, which was lower than those in previously reported series in Western countries. These results suggest that 1) there is a difference in PAC responsiveness to postural stimulation tests and to metoclopramide injection between Japanese and Western patients; and 2) the difference in the metoclopramide-induced aldosterone response implies a relative reduction of tonic dopaminergic inhibition of aldosterone secretion in our Japanese patients with aldosterone-producing adenoma.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8408449&dopt=Abstract












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