Effect of cyclosporine administration on renal hemodynamics in conscious rats

B. M. Murray, Mark S Paller, T. F. Ferris

Research output: Contribution to journalArticle

383 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)767-774
Number of pages8
JournalKidney international
Volume28
Issue number5
DOIs
StatePublished - Jan 1 1985

Fingerprint

Cyclosporine
Hemodynamics
Renal Circulation
Kidney
Vascular Resistance
Vasoconstriction
Prostaglandins F
Renin
Meclofenamic Acid
Phenoxybenzamine
Cyclooxygenase Inhibitors
Captopril
Sympathetic Nervous System
Vasoconstrictor Agents
Denervation
Angiotensin II
Prostaglandins

Cite this

Effect of cyclosporine administration on renal hemodynamics in conscious rats. / Murray, B. M.; Paller, Mark S; Ferris, T. F.

In: Kidney international, Vol. 28, No. 5, 01.01.1985, p. 767-774.

Research output: Contribution to journalArticle

Murray, B. M. ; Paller, Mark S ; Ferris, T. F. / Effect of cyclosporine administration on renal hemodynamics in conscious rats. In: Kidney international. 1985 ; Vol. 28, No. 5. pp. 767-774.
@article{7199233015224e6ca219ea5b121522f1,
title = "Effect of cyclosporine administration on renal hemodynamics in conscious rats",
abstract = "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.",
author = "Murray, {B. M.} and Paller, {Mark S} and Ferris, {T. F.}",
year = "1985",
month = "1",
day = "1",
doi = "10.1038/ki.1985.196",
language = "English (US)",
volume = "28",
pages = "767--774",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Effect of cyclosporine administration on renal hemodynamics in conscious rats

AU - Murray, B. M.

AU - Paller, Mark S

AU - Ferris, T. F.

PY - 1985/1/1

Y1 - 1985/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0022392306&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022392306&partnerID=8YFLogxK

U2 - 10.1038/ki.1985.196

DO - 10.1038/ki.1985.196

M3 - Article

C2 - 3910916

AN - SCOPUS:0022392306

VL - 28

SP - 767

EP - 774

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 5

ER -