Prostaglandins are key modulators of blood pressure and arterial tone. Prostaglandin E
2
(PGE
2
), is a prostanoid that has vasodepressor effects; however, under certain circumstances PGE
2
can induce vasopressor responses. Recent reports demonstrated that sub-threshold concentrations of vasoconstrictors augment PGE
2
-mediated constriction in rat femoral arteries. However, whether angiotensin II (Ang II) could affect PGE
2
-mediated contraction is not known. Using a wire myograph, we demonstrated that PGE
2
had no significant effect on mouse femoral arterial rings at doses up to 1 μM. However, priming of arterial rings with 1 nM Ang II potentiated PGE
2
-evoked constriction in a concentration dependent manner (Area Under the Curve, AUC
untreated
1.784 ± 0.353, AUC
Ang II
23.27± 9.820, P<0.05). We tested femoral arteries from EP1, EP2, and EP3 receptor knockout mice. Only the EP3-/- arteries were unable to respond to PGE
2
after Ang II priming (figure below). Pretreatment of arterial rings with 1 μM losartan, an angiotensin receptor antagonist, blocked PGE
2
-induced constrictor effects primed with Ang II (% of KCl, Ang II 21.72 ± 5.296, Ang II + losartan 3.025 ± 1.046, n=3). We have determined that re-addition of extracellular Ca
2+
to a Ca
2+
-free artery restores PGE
2
-induced contractions (n=5) and that the Rho-kinase inhibitor Y-27632 blocks contraction (n=3). Taken together these data are consistent with angiotensin AT1 and prostaglandin EP3 receptors mediating a synergistic Rho-kinase-dependent contractile response. We are continuing to investigate the relationship between Ang II and PGE
2
to determine the physiological relevance this may have in modulating blood pressure.
Renal microvascular actions of calcitonin gene-related peptide