title: Evidence for attenuation of myo-inositol uptake, phosphoinositide turnover and inositol phosphate production in aortic vasculature of rats during pregnancy.
abstract: 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 [3H]myo-inositol and [3H]glycerol into phosphoinositides of aortae from pregnant rats in vitro was significantly reduced, when compared with vessels from virgin animals. After injection of [3H]myo-inositol intravenously into chronically instrumented conscious pregnant and virgin rats, the incorporation of the label by phosphatidylinositol was 66 +/- 4% less in aortae of gravid versus virgin animals (P less than 0.001), despite comparable plasma concentrations of radioactivity. Fold stimulation of total [3H]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 [3H]inositol trisplus tetrakisphosphate was reduced in aortae from gravid rats, when compared with vessels from virgin animals (P less than 0.005). By HPLC, greater than 90% of the radioactivity in the [3H]inositol trisplus tetrakisphosphate column fraction after 30 and 60 s of agonist stimulation was [3H]inositol-1,4,5-trisphosphate. We further observed that the rate of uptake of [3H]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 less than 0.03). We conclude that myo-inositol uptake and content, phosphoinositide turnover, and inositol phosphate production are reduced in aortic vasculature of gravid rats.
authors.affiliation: Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756.
authors.forename: K P
authors.initials: KP
authors.lastname: Conrad
authors.forename: S A
authors.initials: SA
authors.lastname: Barrera
authors.forename: P A
authors.initials: PA
authors.lastname: Friedman
authors.forename: V M
authors.initials: VM
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000494:pharmacology; D005260:Female; D007294:Inositol / Q000378:metabolism*; D007295:Inositol Phosphates / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats
chemical_list: D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D001127:Arginine Vasopressin; D007294:Inositol