Increased NO-mediated and reduced TxA2-dependent responses in skeletal muscle arterioles in pregnancy

The contribution of skeletal muscle microvessels to pregnancy-induced decrease in peripheral vascular resistance and its underlying mechanisms are not fully understood. We aimed to test the hypothesis that pregnancy enhances arteriolar dilation and reduces constriction by increasing NO-mediation and decreasing reactivity to TxA2. Thus, changes in diameter of isolated, pressurized gracilis muscle arterioles (d: approximately 180 microm) of non-pregnant (NP) and pregnant (P) rabbits to vasoactive agents were measured by videomicroscopy. Acetylcholine (ACh) elicited significantly greater dilations in P than in NP arterioles that could be inhibited by L-NAME, a NO synthase blocker. Dilations to the NO donor SNP did not differ between P and NP arterioles. Constrictions to norepinephrine and the TxA2 receptor agonist U46619 were significantly attenuated in P as compared to NP arterioles. L-NAME increased norepinephrine-induced arteriolar constrictions eliminating the difference between responses of NP and P arterioles. L-NAME enhanced constrictions to U46619 in P and NP arterioles, but the constrictions were still greater in NP vessels. The number of vascular TxA2 receptors-characterized by the TxA2 analog [125I]-BOP in aortic membrane preparations-was significantly less in P as compared to NP rabbits (NP: 284 +/- 83, P: 62 +/- 14 fmol/mg protein, p<0.01). Thus, pregnancy up-regulates endothelial NO- and down regulates TxA2-mediation of responses of skeletal muscle arterioles. These changes in the local regulation of microvascular tone are likely to favor a dilated state of skeletal muscle arterioles, which may contribute to the decreased peripheral vascular resistance during normal pregnancy.