Effect of cyclosporine administration on renal hemodynamics in conscious rats

The effect of acute and chronic administration of cyclosporine on systemic and renal hemodynamics was studied in conscious rats. Infusion of cyclosporine in a dose of 20 mg/kg (Cy 20) resulted in a significant fall in renal blood flow (RBF) (3.4 vs. 6.5 ml/min/g, P < 0.05) and a rise in renal vascular resistance (RVR) (36.9 vs. 20.6 mm Hg/ml/min/g, P < 0.05). Infusion of cyclosporine at a dose of 10 mg/kg (Cy 10) did not result in a significant change in RBF or RVR. Both doses of cyclosporine resulted in stimulation of plasma renin activity (PRA) from control values of 5.6 ± 0.8 ng/ml/hr to 11.6 ± 2.0 with 10 mg/kg and 26.7 ± 5.6 with 20 mg/kg. Urinary 6-keto-PGF(1α) excretion increased from control values of 14.0 ± 2.0 ng/6 hr to 22.7 ± 2.2 with 10 mg/kg and 25.0 ± 2.0 with 20 mg/kg. Similar effects on RBF, RVR, PRA, and 6-keto-PGF(1α) excretion were seen after chronic administration of cyclosporine (20 mg/kg i.p. for 7 days). Pretreatment of animals with captopril did not prevent the fall in RBF after cyclosporine, suggesting that the vasoconstriction was not mediated by angiotensin II. Animals treated with meclofenamate demonstrated reduction in RBF with 10 mg/kg cyclosporine (4.3 vs. 7.0 ml/min/g, P < 0.05), suggesting that prostaglandins protect against the vasoconstrictor effect of cyclosporine. Administration of phenoxybenzamine after cyclosporine improved RBF (5.0 vs. 3.4 ml/min/g) and restored RVR to normal. Similarly, renal denervation dramatically reduced the fall in RBF after cyclosporine (innervated right kidney 3.6 vs. denervated left kidney 6.0 ml/min/g, P < 0.001). We conclude that cyclosporine causes renal vasoconstriction, which is mediated by the renal sympathetic nervous system, and that vasoconstriction is exacerbated by the administration of cyclooxygenase inhibitors.