Inhibition of Rho‐kinase decreases fetoplacental perfusion pressure under both normoxic and hypoxic conditions

Abstract

Acute hypoxia causes hypoxic fetoplacental vasoconstriction (HFPV). Rho‐kinase inhibits myosin phosphatase activity and therby modulates intracellular Ca2+ sensitivity of vascular smooth muscle and augments vasoconstriction. We tested whether inhibition of Rho‐kinase pathway in fetoplacental vessels inhibits HFPV. Isolated rat placenta was dually perfused (from both the maternal and fetal side) with physiologic salt solution saturated with normoxic gas mixture in constant flow rate. Rho‐kinase pathway was inhibited by Fasudil (10 μM) which caused significant decrease of fetoplacental perfusion pressure (from 38 ± 3 mmHg to 31 ± 3 mmHg, P < 0,01). Vasoconstriction induced by the acute hypoxic challenge was blocked. We measured fetoplacental perfusion pressure and fetoplacental vascular resistance as a relationship of vascular perfusion pressure to continually rising flow rate (P/Q). In acute hypoxia the slope of the P/Q relation was higher in the control group than in the group with Fasudil. The pressure axis intercepts with P/Q line did not differ. In summary, Rho‐kinase inhibition causes complete abolition of HFPV.Supported by GACR 305/08/0108 and 2nd Faculty of Medicine, Charles University