Role of prostaglandins and thromboxane in the control of renal hemodynamics in experimental liver cirrhosis.
Although there is considerable evidence that vasodilator prostaglandins such as prostaglandin E2 (PGE2) modulate renal hemodynamics in liver cirrhosis, the role of the vasoconstrictor thromboxane A2 (TXA2) is controversial. We measured renal hemodynamics and glomerular eicosanoid production in cirrhotic and control rats. Renal plasma flow, as estimated by para-aminohippurate clearance (CPAH) and glomerular filtration rate, as determined by inulin clearance (CIN), were comparable between groups; glomerular production of PGE2 and TXA2 (estimated by the metabolite thromboxane B2 [TXB2]) was slightly but not significantly higher in cirrhotic than in control rats (PGE2: 1060 +/- 142 pg/mg glomerular protein vs 854 +/- 288 pg/mg glomerular protein; TXB2: 782 +/- 103 pg/mg glomerular protein vs 468 +/- 104 pg/mg glomerular protein). Addition of serum from cirrhotic rats to the incubation media failed to increase eicosanoid production in glomeruli obtained from either cirrhotic or control rats. Cyclooxygenase inhibition with 5 mg/kg indomethacin, a dose sufficient to result in a 68% inhibition of glomerular PGE2 synthesis, decreased both CPAH (from 6.59 +/- 0.69 ml/min to 4.52 +/- 0.67 ml/min, p less than 0.05) and CIN (from 1.34 +/- 0.16 ml/min to 0.68 +/- 0.07 ml/min, p less than 0.01) in cirrhotic rats. Thromboxane synthesis inhibition with 1 mg/kg UK-38485, which resulted in an 84% decrease in glomerular TXB2, did not significantly affect either CPAH or CIN; however, there was a strong trend toward improvement in CIN (from 1.23 +/- 0.11 ml/min to 1.43 +/- 0.15 ml/min (0.05 less than p less than 0.1). Neither drug affected renal hemodynamics in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Leehey
D J
DJ
Department of Medicine, Hines Veterans Administration Hospital, IL 60141.
Uckerman
M T
MT
Rahman
M A
MA
D000818:Animals; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D013931:Thromboxanes / Q000096:biosynthesis / Q000502:physiology*
D007093:Imidazoles; D011453:Prostaglandins; D013931:Thromboxanes; C039242:dazmegrel; D007213:Indomethacin