Influence of eicosanoids on renal function of DOCA-salt hypertensive rats.
The present study examined the contribution of changes in the synthesis or degradation (or both) of renal eicosanoids to the alterations in renal hemodynamics observed in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Renal blood flow and glomerular filtration rate were markedly reduced in DOCA-salt hypertensive rats compared with values observed in control rats given water or saline to drink. The abnormalities in renal hemodynamics in the hypertensive rats were associated with an increase in the excretion of thromboxane B2, an increase in the release of thromboxane B2 from renal cortical tissue slices, and a diminished release of prostaglandin E2 (PGE2) from renal medullary tissue. Additionally, the urinary excretion of PGE2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and the release of 6-keto-PGF1 alpha from renal cortical and medullary tissue were elevated in rats with DOCA-salt hypertension. Since the excretion of PGE2 and 6-keto-PGF1 alpha and the release of 6-keto-PGF1 alpha by medullary tissue were also elevated in normotensive rats given 1% NaCl solution to drink, these latter changes probably were related to an elevation of sodium intake rather than to the development of hypertension. The functional significance of the alterations in the renal production of thromboxane in DOCA-salt hypertensive rats was evaluated by comparing the effects of a thromboxane synthesis inhibitor and a receptor antagonist on renal function in normotensive and DOCA-salt hypertensive rats. The administration of the thromboxane synthetase inhibitor furegrelate and the thromboxane receptor blocker SQ 29548 had no effect on renal hemodynamics in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
Roman
R J
RJ
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Kaldunski
M L
ML
Mattson
D L
DL
Mistry
M
M
Nasjletti
A
A
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001834:Body Water / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003900:Desoxycorticosterone; D005231:Fatty Acids, Unsaturated; D006439:Hemodynamics / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001572:Benzofurans; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011453:Prostaglandins; D013931:Thromboxanes; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D008469:Meclofenamic Acid; C045749:SQ 29548; D012964:Sodium; C039936:furegrelate