Effects of nitric oxide blockade and cyclosporin A on cardiovascular and renal function in normal man.
OBJECTIVE
The present study investigated whether the nitric oxide (NO) system is involved in cyclosporin A (CsA)-induced changes in cardiovascular and renal function in man.


METHODS
Ten healthy volunteers were investigated twice--with and without intake of a single dose of CsA (8 mg/kg). N(G)-monomethyl-L-arginine (L-NMMA; 3 mg/kg) was injected 4 h after study start on each day.


RESULTS
There was no change in glomerular filtration rate (GFR) on the day without CsA. CsA alone did not change GFR, but after L-NMMA injection, GFR decreased significantly from 101 +/- 4 to 91 +/- 4 ml/min. L-NMMA increased renal vascular resistance with no difference between the two study days. CsA increased significantly the diastolic blood pressure (BP) by 8 +/- 2% and the heart rate (HR) by 30 +/- 4%, without changes in cardiac output L-NMMA further increased BP by around 8%, and decreased HR by 11% and cardiac output by 20% on both study days. L-NMMA decreased urinary flow rate by around 25% and renal sodium clearance from 1.1 to approximately 0.6 ml/min on both study days. CsA decreased plasma renin significantly and increased the urinary excretion rate of prostaglandin E2 (PgE2), 6-keto-prostaglandin F1alpha (6-keto-PgF1alpha) and thromboxane B2(TxB2) when compared to the control day. The urinary excretion rate of NOx and cGMP declined gradually on the control day. In contrast, there was a minor, non-significant increase in NOx and cGMP excretion after CsA, followed by a decrease (29 +/- 2 and 16 +/- 4%, respectively) after L-NMMA in parallel with the decrease in GFR.


CONCLUSIONS
The present findings suggest that NO does not play a major role during acute CsA-induced changes in cardiovascular function and renal haemodynamics in man. Renal NO synthesis, however, may attenuate the acute CsA-induced decrease in GFR.
Hansen
J M
JM
Department of Clinical Physiology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. jmh@rh.dk
Johansen
N J
NJ
Mollerup
H M
HM
Fogh-Andersen
N
N
Strandgaard
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D016572:Cyclosporine / Q000008:administration & dosage*; D015232:Dinoprostone / Q000652:urine; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000652:urine; D012016:Reference Values; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D013929:Thromboxane B2 / Q000652:urine; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D019323:omega-N-Methylarginine; D016718:Arachidonic Acid; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D016572:Cyclosporine; D012964:Sodium; D012083:Renin; D015232:Dinoprostone