ENDOTHELIAL MODULATION OF RENAL INTERLOBAR ARTERIES FROM PREGNANT RATS

The purpose of this study was to determine whether there are gestational effects on 1) the response of resistance arteries from the renal vasculature to phenylephrine and 2) the endothelial modulation of these arteries. Interlobar arteries (200-300 mum ID) were isolated from the kidneys of virgin and pregnant rats at 18-20 days of gestation (term, 22 +/- 1 days) and studied in a pressurized arteriograph system. Intact arteries from virgin and pregnant rats did not differ in sensitivity to phenylephrine. Arteries without endothelium from both groups were more sensitive to phenylephrine than arteries with endothelium. Sensitivity was increased 3.4-fold by endothelial removal in arteries from virgin rats and 1.5-fold in the pregnant group. Concentration-response relationships to phenylephrine were determined in arteries with endothelium and then repeated in the presence of 2.5 x 10(-4) M N(omega)-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase. All arteries were more sensitive to phenylephrine in the presence of L-NNA, with an average increase of 3.2-fold for the arteries from virgin rats and 1.6-fold from pregnant rats. These results indicate that the increased sensitivity to phenylephrine is primarily due to elimination of endothelium-derived relaxing factor (EDRF) and that basal EDRF activity is decreased during late gestation. To determine whether stimulated endothelium-dependent relaxation is enhanced in pregnancy, arteries with endothelium were constricted with phenylephrine to 50% of their maximum and relaxed to increasing concentrations of methacholine. The arteries from pregnant rats were significantly more sensitive to relaxation by methacholine than arteries from virgin rats. Thus stimulated endothelium-dependent relaxation is augmented in arteries from late-pregnant rats. We conclude that while the potential for endothelium-dependent relaxation in the renal vasculature is augmented during late gestation in the rat, the modification of the vasoconstrictor response to phenylephrine by the basal release of EDRF is reduced.