EVIDENCE FOR ATTENUATION OF MYOINOSITOL UPTAKE, PHOSPHOINOSITIDE TURNOVER AND INOSITOL PHOSPHATE PRODUCTION IN AORTIC VASCULATURE OF RATS DURING PREGNANCY

We postulated that vascular phosphoinositide metabolism is attenuated during pregnancy, and thereby could contribute to maternal vasodilation and reduced vascular reactivity. The basal rate of incorporation of [H-3]myo-inositol and [H-3]glycerol into phosphoinositides of aortae from pregnant rats in vitro was significantly reduced, when compared with vessels from virgin animals. After injection of [H-3]myo-inositol intravenously into chronically instrumented concious pregnant and virgin rats, the incorporation of the label by phosphatidylinositol was 66 +/- 4% less in aortae of gravid versus virgin animals (P < 0.001), despite comparable plasma concentrations of radioactivity. Fold stimulation of total [H-3]inositol phosphates by arginine vasopressin, norepinephrine, and angiotensin II over a 15-min period was not different between aortic segments from virgin and gravid rats, although both absolute basal and stimulated levels were significantly less in vessels from pregnant animals. After 45 s of incubation with 10(-7) M arginine vasopressin, however, the fold-stimulation of [H-3]inositol trisplus tetrakisphosphate was reduced in aortae from gravid rats, when compared with vessels from virgin animals (P < 0.005). By HPLC, > 90% of the radioactivity in the [H-3]inositol trisplus tetrakisphosphate column fraction after 30 and 60 s of agonist stimulation was [H-3]inositol-1,4,5-trisphosphate. We further observed that the rate of uptake of [H-3]myo-inositol by aortic vasculature obtained from gravid rats was significantly (24%) less than uptake by vessels from virgin animals. Plasma myo-inositol concentrations were not significantly different, but presumably as a consequence of reduced uptake, aortic segments freshly isolated from pregnant rats contained 22 +/- 6% less myo-inositol than vessels from virgin controls as measured by gas chromatography-mass spectrometry (P < 0.03). We conclude that myo-inositol uptake and content, phosphoinositide turnover, and inositol phosphate production are reduced in aortic vasculature of gravid rats.