Effect of short-term cyclosporine administration in rats on renin-angiotensin and thromboxane A2: possible relevance to the reduction in glomerular filtration rate.
A short-term treatment with Cyclosporine A (CyA) induces a decrease in glomerular filtration rate (GFR), promptly reversible after withdrawal of the drug. Several lines of evidence are now available as to indicate that this phenomenon is dependent on a hemodynamic perturbation resulting in a renal vasoconstriction. With the present work we have examined the relationship between the reduction in GFR which follows a short-term administration of CyA in rats and the biochemical changes in renin-angiotensin system and renal arachidonic acid metabolism. Our results show that CyA administration (25 mg/kg/day) for 45 days stimulates renin-angiotensin system with an increase in plasma renin activity. These changes are not accompanied by a parallel increase in the renal synthesis of vasodilatory prostaglandin E2 and prostacyclin as it occurs in other conditions of renin-angiotensin stimulation. At variance glomerular synthesis and urinary excretion of thromboxane A2 (TxA2) are increased progressively during CyA treatment. These changes in renal Tx precede the increase in serum creatinine and the decrease in GFR thus indicating that TxA2 might be an additional factor potentiating the effect of angiotensin II on glomerular hemodynamics. In conclusion the early reduction in GFR which follows daily administration of CyA in rats might be the result of a synergic action of angiotensin II and TxA2 on vascular tone and mesangial contraction which is not modulated by an increase in glomerular vasodilatory prostaglandins. If this explanation may be applied to early reduction in GFR observed in humans treated with CyA before tubular toxicity develops needs to be investigated further.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D015232:Dinoprostone; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D011453:Prostaglandins / Q000652:urine; D011458:Prostaglandins E / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013928:Thromboxane A2 / Q000097:blood*; D013929:Thromboxane B2 / Q000652:urine
D003524:Cyclosporins; D011453:Prostaglandins; D011458:Prostaglandins E; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D012083:Renin; D015232:Dinoprostone