Thromboxane synthetase inhibition improves function of hydronephrotic rat kidneys

Area of Science:

• Nephrology
• Renal Physiology
• Pharmacology

Background:

• Unilateral ureteral obstruction (UUO) causes sustained renal vasoconstriction.
• Bradykinin stimulates vasoconstrictor thromboxane production in hydronephrotic kidneys.

Purpose of the Study:

• To measure thromboxane and prostaglandin E2 production in UUO rat kidneys.
• To evaluate thromboxane synthetase inhibitors for treating UUO-induced renal dysfunction.

Main Methods:

• Ex vivo perfusion of hydronephrotic rat kidneys.
• In vitro and in vivo assessment of thromboxane synthetase inhibitors (imidazole, UK 37248, UK 38485).
• Measurement of renal hemodynamics and excretory function.

Main Results:

• UUO kidneys showed increased basal and bradykinin-stimulated thromboxane and prostaglandin E2 production.
• Substituted imidazoles were potent thromboxane synthetase inhibitors in vitro.
• In vivo, UK 37248 and UK 38485 significantly improved renal blood flow and function in UUO kidneys.

Conclusions:

• The hydronephrotic rat kidney produces elevated levels of the vasoconstrictor thromboxane.
• Thromboxane is a key mediator of vasoconstriction in this UUO model.
• Thromboxane synthetase inhibition offers a potential therapeutic strategy for obstructive nephropathy.