The role of thromboxane in two-kidney, one-clip Goldblatt hypertension in rats.
Impaired contralateral kidney (CLK) function is important in the maintenance of hypertension in the two-kidney, one-clip (2K, 1C) Goldblatt rat model. Since glomerular filtration rate (GFR) is influenced by the products of arachidonic acid metabolism, we investigated the potential role of eicosanoids as mediators of impaired CLK pressure-volume regulation. At 4 wk following right renal artery clipping, GFR of hypertensive rats was significantly reduced. This decrease was due to the fixed reduction in GFR of the clipped kidney and failure of the CLK to increase its GFR. Thromboxane (Tx) production by isolated perfused CLK was significantly elevated, whereas prostacyclin production remained unchanged. Furthermore, CLK GFR was inversely proportional to Tx production. Treatment of 4-wk hypertensive animals with either the Tx synthase inhibitor UK-38,485 or the Tx receptor antagonist GR 32191 produced a significant increase in CLK GFR. In addition, treatment with either the Tx synthase inhibitor or the Tx receptor antagonist significantly reduced systemic blood pressure. Thus, in this 2K, 1C model of hypertension, increased renal Tx production prevents functional hypertrophy of the contralateral kidney. As a result, CLK pressure-volume regulation is impaired and systemic hypertension is maintained. Furthermore, Tx antagonists restore CLK function and acutely lower systemic blood pressure. Therefore, increased renal Tx production by the CLK appears to be an important mediator of hypertension in the 2K, 1C model.
Himmelstein
S I
SI
Department of Medicine, Duke University, Durham, North Carolina.
Klotman
P E
PE
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure; D005919:Glomerular Filtration Rate; D006538:Heptanoic Acids / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D012016:Reference Values; D012039:Regional Blood Flow; D012079:Renal Circulation; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000502:physiology*
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D007093:Imidazoles; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; C039242:dazmegrel; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase; C060013:vapiprost