Vasoconstrictor prostanoids

Abstract

In cardiovascular diseases and during aging, endothelial dysfunction is due in part to the release of endothelium-derived contracting factors that counteract the vasodilator effect of the nitric oxide. Endothelium-dependent contractions involve the activation of endothelial cyclooxygenases and the release of various prostanoids, which activate thromboxane prostanoid (TP) receptors of the underlying vascular smooth muscle. The stimulation of TP receptors elicits not only the contraction and the proliferation of vascular smooth muscle cells but also diverse physiological/pathophysiological reactions, including platelet aggregation and activation of endothelial inflammatory responses. TP receptor antagonists curtail endothelial dysfunction in diseases such as hypertension and diabetes, are potent antithrombotic agents, and prevent vascular inflammation.

Mechanisms Underlying Enhanced Noradrenaline-Induced Femoral Arterial Contractions of Spontaneously Hypertensive Rats: Involvement of Endothelium-Derived Factors and Cyclooxygenase-Derived Prostanoids

“…20,23,30,39) Moreover, COX-derived substances exert two opposite responses, namely vasodilation (i.e., PGI 2 ) and vasoconstriction. 24,25,40) To evaluate which components are altered in the SHR femoral artery, we assessed concentration-response curves for ACh in the presence of various inhibitors to block the aforementioned components (Fig. 3).…”

“…20,21) However, other factors including endothelium-derived hyperpolarizing factor (EDHF) and cyclooxygenase (COX)-derived prostanoids can also modulate vascular tone. [22][23][24][25] Indeed, there are several reports suggesting that contraction induced by various substances including alpha-adrenoceptor ligands is enhanced by the inhibition of EDHF signaling 26) and enhanced 27) or suppressed 11,28,29) by COX signaling in various arteries under a (patho) physiological state. Because prostacyclin (PGI 2 ) serves as an endothelium-derived vasodilator and vasoconstrictor depending on the vessel type, species, or disease condition, 4,9,30) the exact role of COX-derived prostanoids to regulate vascular tone is complicated in cardiovascular diseases including hypertension.…”

Effect of Short-term Polyphenol Treatment on Endothelial Dysfunction and Thromboxane A₂ Levels in Streptozotocin-Induced Diabetic Mice

“…The endothelium plays a central role in physiological maintenance of the vascular function by regulating vascular tone, leukocyte adhesion, and platelet activation, as a result of the release of vasoactive substances such as nitric oxide (NO), prostacyclin, and thromboxane A 2 (TXA 2 ). 1,[6][7][8][9][10][11][12][13][14][15][16] Several natural polyphenols have been evaluated for their ability to protect against endothelial dysfunction and, thus, for their effectiveness in preventing cardiovascular disease. 17) Indeed, we have also shown that long-term chlorogenic acid (CA) treatment (2 months) can normalize the impaired endothelium-dependent relaxation seen in diabetic rats.…”

Thromboxane Receptors in Smooth Muscle Promote Hypertension, Vascular Remodeling, and Sudden Death

“…22 To determine whether loss of TP receptors in VSMCs affected this response, we compared systemic vasoconstrictor responses in anesthetized TP-SMKOs and controls. As shown in Figure 1, we observed robust vasoconstriction in response to acute administration of the TP receptor agonist (100 µg/kg of U46619) in the controls.…”