Hemodynamic and renal effects of U-46619, a TXA2/PGH2 analog, in late-pregnant rats

The vasoconstrictor effects of pressor agents are attenuated during pregnancy. Thromboxane A2 (TXA2) is produced in great quantities during hypertension in pregnancy, and therefore it is important to know whether pregnancy modifies the pressor effects of TXA2. The TXA2 analog U-46619 was infused in anesthetized, acutely prepared and conscious, chronically prepared late-pregnant and nonpregnant female rats to examine its systemic hemodynamic and renal effects. Mean arterial pressure (MAP) and total peripheral resistance (TPR) were lower in anesthetized pregnant than nonpregnant rats (P < 0.01). The infusion of U-46619 into the aortic arch resulted in elevation of MAP only in pregnant rats, due to a greater elevation of TPR (60 +/- 17%) compared with nonpregnant rats (36 +/- 6%, P < 0.05). The pressor effect of intravenously infused U-46619 was also enhanced in conscious pregnant versus nonpregnant rats, and the increase in renal vascular resistance was undiminished. U-46619 increased hematocrit and plasma protein concentration more during pregnancy, which suggested greater reduction of plasma volume. The urinary excretion of sodium (-1.49 +/- 0.25 vs. -0.54 +/- 0.24 micromol/min) and water was reduced more in pregnant than nonpregnant rats during U-46619 (P < 0.01). Thus the MAP and renal effects of the TXA2 analog are exaggerated during pregnancy in the rat.