Perivascular adipose tissue (PVAT)‐mediated buffering of vasoconstriction in placental ischemia‐induced hypertensive rats

Abstract

Preeclampsia is a pregnancy-specific hypertensive disorder diagnosed along with systemic endothelial and vascular dysfunction. A novel regulator of vascular tone is the perivascular adipose tissue (PVAT) that surrounds most blood vessels and functions to blunt vasoconstriction. However, it is unknown whether PVAT becomes dysfunctional in preeclampsia. Preeclampsia arises from placental ischemia to elicit release of pro-vasoconstrictive factors into the maternal circulation. In this study, it was hypothesized that placental ischemic rats have attenuated PVAT-mediated buffering of vasoconstriction. Placental ischemia was induced on gestational day 14 in Sprague-Dawley rats by conducting the Reduced Uterine Perfusion Pressure (RUPP) protocol. Conscious blood pressure measurements (carotid catheter) and wire myography were conducted on day 19. Mean arterial blood pressure was significantly elevated (P<0.05) in RUPP (N=6, 117±3 mmHg) vs. Pregnant (N=6, 97±3 mmHg) rats. In aortas, the maximum response (as % increase in force from baseline tension) to KCl-induced depolarization was not affected (P>0.05) by RUPP or the presence of PVAT: Pregnant+PVAT (43±9%) vs. Pregnant-PVAT (42±5%) and RUPP+PVAT (42±%7) vs. RUPP-PVAT (48±7%). Furthermore, phenylephrine (Phe, alpha1-adrenergic receptor agonist)-induced vasoconstriction was similar (P>0.05) in Pregnant+PVAT (69±11%) vs. Pregnant-PVAT (70±12%) and RUPP+PVAT (38±12%) vs. RUPP-PVAT (34±9%), with the 2-way ANOVA detecting a main effect only for RUPP (P<0.05). It was then assessed whether the endothelium controls PVAT function whereby denuding the endothelium did not impact (P>0.05) any of the respective Phe responses in Pregnant+PVAT-Endo (60±12%), Pregnant-PVAT-Endo (72±11%), RUPP+PVAT-Endo (30±15%), or RUPP-PVAT-Endo (22±7%). In smaller, third-order mesenteric arteries, direct depolarization by KCl responses were similar (P>0.05) between Pregnant+PVAT (176±19%), Pregnant-PVAT (149±17%), RUPP+PVAT (148±30%), and RUPP-PVAT (167±27%). As for Phe, the 2-way ANOVA identified a main effect (P<0.05) only for PVAT to blunt Phe-induced vasoconstriction in Pregnant+PVAT (259±38%) vs. Pregnant-PVAT (337±26%) and RUPP+PVAT (176±39%) vs. RUPP-PVAT (379±47%), with no difference for the influence of PVAT between RUPP and Pregnant groups. Removal of the endothelium further attenuated Phe responses in the PVAT groups: Pregnant+PVAT-Endo (174±66%) and RUPP+PVAT-Endo (-3±3%) vs. their respective groups without PVAT: Pregnant-PVAT-Endo (379±39%) and RUPP-PVAT-Endo (339±167%). In fact, the degree of this attenuation to Phe-induced vasoconstriction was the greatest (P<0.05) in the RUPP+PVAT-Endo (-104±3%) group compared all other groups: RUPP-PVAT-Endo (19±59%), Pregnant+PVAT-Endo (10±11%), and Pregnant-PVAT-Endo (10±11%). In conclusion, as it was found that removal of the endothelium allows for enhanced PVAT blunting of vasoconstriction in RUPP rats, these data indicate that placental ischemia drives endothelial dysfunction to subsequently disrupt PVAT function in small arteries during pregnancy.