Influence of cyclosporine A (CSA) on intrarenal control of GFR.
In the acute clinical situation, CSA produces reversible renal impairment. Studies by Morris et al. [1982] and others indicate that this is rapidly reversible when the drug is ceased. A series of studies have been performed in rats with the aim of examining changes in GFR, together with changes in the intrarenal renin-angiotensin system and renal release of prostaglandins. Rats were treated for 3-7 days with CSA and at the end of the experiment kidneys were removed and renal cortical slices prepared. There was increased renin secretion from the CSA-treated rats, compared to controls, and the response was dose-dependent. There was an increase in renal cortical renin content paralleling the renin release. Determinations of plasma renin in these animals also indicated a rise in plasma renin activity associated with time. In animals not pretreated with CSA, the renal cortical slices incubated with CSA demonstrated a stimulation of renin release. A further group of rats pretreated with 100 mg/kg/day of CSA for 3-7 days showed no change in renal slice release of 6-keto-PGF1 alpha, thromboxane B2, PGE2 and PGF2 alpha. This data indicates that the renal renin-angiotensin system is activated by CSA and produces a dissociation of the linkage between renal slice prostaglandin release and the renin angiotensin system. This would indicate that CSA affects the intrarenal control of GFR. However, the exact site of the modulation remains to be determined.
Duggin
G G
GG
Baxter
C
C
Hall
B M
BM
Horvath
J S
JS
Tiller
D J
DJ
D000818:Animals; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000633:toxicity*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D011453:Prostaglandins / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects
D003524:Cyclosporins; D011453:Prostaglandins; D003404:Creatinine