Abstract Body (Do not enter title and authors here): Evidence suggests that cerebrovascular disease is a leading cause of morbidity and mortality in women with preeclampsia (PE), however the mechanisms are unknown. In a transgenic rat displaying PE-like syndrome (TGA-PE: female transgenic for angiotensinogen mated to male transgenic for renin), we have shown postpartum alterations in cerebrovascular hemodynamics suggesting dysfunctional autoregulation. We hypothesize that impaired middle cerebral artery (MCA) reactivity contributes to the cerebrovascular dysfunction in this model. High frequency ultrasound was used to determine the pulsatility index (PI) of left MCA (LMCA). Vascular responses were studied in isolated segments of LMCA from SD (n=12) and TGA-PE (n=8) two months post-delivery. Arteries were mounted on a Multi-Wire Myograph for determination of isometric force (USA-DMT). The contractile responses to K75 mM and endothelin-1 (ET-1, 10^-10-10^-7M) were measured in basal tone. Vasodilatory responses to acetylcholine (ACh, 10^-11-10^-4M)) were determined in arteries pre-constricted with the thromboxane agonist U46619 (10^-7M); the maximal response (R) and sensitivity (pD₂=-Log[EC₅₀]) were analyzed.
Our data show that systolic blood pressures were elevated in TGA-PE versus SD at 2 months post-delivery (144.9±2.7 vs. 118.4±2.5, p<0.05; n=10-19). However, the PI was lower in TGA-PE vs. SD (0.96±0.05 vs.1.31±0.06; p<0.05, n=8-13). No differences in basal tone of MCA segments were observed, whereas TGA-PE arteries displayed a lower optimal diameter (175±4 μm vs. 217±4μm; p<0.05) and a lower response to K (0.85±0.11 vs. 1.29±0.1 mN/mm; p<0.05) compared to SD. Vasodilatation to acetylcholine was similar (ACh_MAX 79±8 vs. 70±9%) with a lower sensitivity (pD2 5.2±0.1 vs.6.7±0.4; p<0.05) in TGA-PE. The contractile response to ET-1 was increased in TGA-PE arteries (ET-1_MAX 159±7 vs. 129±6 % K_MAX; p<0.05) with no differences in sensitivity (pD2 8.8±0.1 vs. 8.9±0.1).
Our data demonstrate structural and functional differences in MCA from TGA-PE vs. SD at 2 months postpartum. In addition to a smaller functional diameter, a lower non-receptor dependent contraction may explain the lower resistance of MCA observed in the preeclamptic model. We conclude that attenuated vasodilatory and increased contractile responses of MCA could promote cerebrovascular dysfunction in this model, and that these adaptations may contribute to cerebrovascular pathology in postpartum preeclamptic state. Supported by NIH 1R01HL155420