Effects of a prostacyclin analog iloprost on kidney function, renin-angiotensin and kallikrein-kinin systems, prostanoids and catecholamines in man.
Iloprost (ZK 36 374), a stable analog of carbaprostacyclin, was infused for 72 h to nine patients with advanced obliterative arterial disease. Iloprost caused a marked vasodilation and a compensatory increase in cardiac output. The glomerular filtration rate increased by 45% and tubular reabsorption of sodium and water were reduced by 80% and 107%, respectively. The urine excretion rate increased by 122%. Tubular handling of potassium and calcium were not influenced by iloprost but magnesium reabsorption was stimulated. The renin-angiotensin system was not activated while serum angiotensin converting enzyme activity was decreased. Kallikrein excretion in urine was increased 4.4-fold but plasma kininogen, a substrate for kallikrein in producing vasoactive kinins, was unaffected by the drug. Plasma levels of 6-keto-PGF1 alpha and TxB2 were decreased and their excretion in urine increased. Plasma catecholamines were not changed by iloprost. Several of the changes persisted for at least the first postinfusion day. The results indicate that iloprost increases urine excretion rate by increasing glomerular blood flow and by inhibiting sodium and water reabsorptions. The kinin-forming system, but not the renin-angiotensin system or plasma catecholamines, may be activated. The decrease in plasma level of prostanoids can be, at least partly, due to their increased excretions in urine.
P
P
Ylitalo
S
S
Kaukinen
A K
AK
Nurmi
E
E
Seppälä
T
T
Pessi
H
H
Vapaatalo
D000328:Adult; D000368:Aged; D001162:Arteriosclerosis Obliterans / Q000188:drug therapy / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D016285:Iloprost; D007610:Kallikreins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007705:Kinins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*
D002395:Catecholamines; D007705:Kinins; D011453:Prostaglandins; D011464:Epoprostenol; D007610:Kallikreins; D016285:Iloprost