Diverse effects of prostaglandin E2 on vascular contractility

Abstract

Prostaglandin E₂ (PGE₂) is a major prostanoid produced under inflammatory situations. There have been controversial reports showing contractile or relaxant effect of PGE₂ on vascular tone in various types of blood vessels. Thus, it is still elusive whether and how PGE₂ modulates vascular tone. We here assessed the effects of PGE₂ on vascular contractility using different types of vasculatures isolated form rat. In endothelium-denuded aortas and mesenteric arteries, PGE₂ (1 nM-10 μM) concentration-dependently enhanced the contraction elicited by K(+) (35.4 mM) or norepinephrine (10 nM). In pulmonary arteries, PGE₂ did not alter the both-induced contraction. Tail arteries were relaxed by a low dose of PGE₂ (1-100 nM), but this response shifted to contraction by the higher dose of PGE₂ (300 nM-10 μM). There are four types of PGE₂ receptors EP1-4. RT-PCR showed that aortas and mesenteric arteries abundantly expressed EP3, while tail arteries abundantly expressed EP4. We next revealed that selective EP3 agonism enhanced the contraction in mesenteric arteries, whereas EP4 agonism induced relaxation in tail arteries. Taken together, PGE₂ causes different contractile responses depending on the type of vascular bed. This phenomenon may be due to the difference in expression pattern and activity of EP receptors.

Multiple roles of the PGE2‐EP receptor signal in vascular permeability

“…EP 3 receptor stimulation enhanced the endothelial barrier and suppressed vascular permeability without affecting the contraction of mural cells or local blood flow. We previously reported that an EP 3 receptor agonist induced contraction in large or splanchnic arteries, while it did not influence contraction in small arteries, for example the tail artery (Kobayashi et al ., ; Kida et al ., ). Smooth muscle cells in small vessels are unlikely to be responsive to EP 3 receptor‐mediated signalling.…”

“…Data are presented as means ± SEM. ◀ reported that an EP3 receptor agonist induced contraction in large or splanchnic arteries, while it did not influence contraction in small arteries, for example the tail artery (Kobayashi et al, 2011;Kida et al, 2014). Smooth muscle cells in small vessels are unlikely to be responsive to EP3 receptor-mediated signalling.…”

Prostaglandin E2sequentially activates E‐prostanoid receptor‐3 and thromboxane prostanoid receptor to evoke contraction and increase in resistance of the mouse renal vasculature

“…This suggests that EP3’s vasoconstrictor activity can blunt effects of vasodilator EPs (EP2 and/or 4) to take a part in PGE 2 ‐mediated control of renal blood flow or systemic blood pressure. Indeed, PGE 2 is found to evoke contractions of some isolated vessels that are inhibited by antagonizing EP3 . However, vasoconstrictor responses of isolated vessels to PGE 2 are also found to be abolished by TP antagonism .…”

“…Indeed, PGE 2 is found to evoke contractions of some isolated vessels that are inhibited by antagonizing EP3. [14][15][16] However, vasoconstrictor responses of isolated vessels to PGE 2 are also found to be abolished by TP antagonism. 17,18 Moreover, we have recently shown that TP −/− removes most of the contraction evoked by PGE 2 in mouse abdominal aorta.…”

Inflammatory Effects of Bothrops Phospholipases A2: Mechanisms Involved in Biosynthesis of Lipid Mediators and Lipid Accumulation

“…PGE 2 and PGD 2 are important modulators of vasodilation, and PGE 2 can potentiate an increase in vascular permeability, promoted by mediators of this phenomenon, with a consequent formation of edema [188,189]. Studies using pharmacological treatment with non-steroidal anti-inflammatory compounds were crucial in demonstrating the participation of these COXs-derived lipid mediators on edema [126,190] and hyperalgesia [135], induced by B. asper sPLA 2 s. In addition, studies demonstrating that MT-III and MT-II upregulated COX-2 protein expression in peritoneal leukocytes without altering the constitutive expression of COX-1 evidenced the ability of these venom PLA 2 s to influence downstream cyclooxygenase isozymes and suggested this as a mechanism by which these sPLA 2 s induced the production of prostaglandins [162,163].…”