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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thromboxane A2 (TxA2) plays a very important role in various cardiovascular diseases through its action on platelet aggregation, vasoconstriction, and proliferation. The present article focuses on the role of TxA2 signaling in endothelium-dependent contractions of arteries. Arachidonic acid (AA) is metabolized by cyclooxygenase (COX) to form the unstable prostaglandin H2 which is further converted into TxA2. After being produced by thromboxane synthase (TxAS), TxA2 ultimately stimulates TxA2/prostanoid (TP) receptor to induce vasoconstriction. The calcium ionophore A23187, the prostanoid precursor AA, or the muscarinic receptor agonist acetylcholine (ACh) can evoke endothelium-dependent contractions associated with TxA2. The endothelium-dependent contractions shown in hypertension, diabetes, atherogenesis, and other cardiovascular diseases have been significantly reduced by antagonism of COX, TxAS, or TP receptor. So inhibition of the bioavailability and/or effect of TxA2 may be promising therapeutic targets to prevent these diseases. Especially some bioactive compounds isolated from medicinal plants will provide new pharmacological approaches to promote vascular health.
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PMID:Role of thromboxane A2 signaling in endothelium-dependent contractions of arteries. 2918 71

Plasma levels of the vasoactive substance uridine adenosine tetraphosphate (Up4A) are elevated in hypertensive patients and Up4A-induced vascular contraction is exacerbated in various arteries isolated from hypertensive animals, suggesting a potential role of Up4A in development of hypertension. We previously demonstrated that Up4A produced potent and partially endothelium-dependent relaxation in the porcine coronary microvasculature. Since pressure-overload is accompanied by structural abnormalities in the coronary microvasculature as well as by endothelial dysfunction, we hypothesized that pressure-overload blunts the coronary vasodilator response to Up4A, and that the involvement of purinergic receptors and endothelium-derived factors is altered. The effects of Up4A were investigated using wire-myography in isolated coronary small arteries from Sham-operated swine and swine with prolonged (8 weeks) pressure overload of the left ventricle induced by aortic banding (AoB). Expression of purinergic receptors and endothelium-derived factors was assessed in isolated coronary small arteries using real-time PCR. Up4A (10-9 to 10-5 M) failed to produce contraction in isolated coronary small arteries from either Sham or AoB swine, but produced relaxation in preconstricted arteries, which was significantly blunted in AoB compared to Sham. Blockade of purinergic P1, and P2 receptors attenuated Up4A-induced coronary relaxation more, while the effect of P2X1-blockade was similar and the effects of A2A- and P2Y1-blockade were reduced in AoB as compared to Sham. mRNA expression of neither A1, A2, A3, nor P2X1, P2X7, P2Y1, P2Y2, nor P2Y6-receptors was altered in AoB as compared to Sham, while P2Y12 expression was higher in AoB. eNOS inhibition attenuated Up4A-induced coronary relaxation in both Sham and AoB. Additional blockade of cyclooxygenase enhanced Up4A-induced coronary relaxation in AoB but not Sham swine, suggesting the involvement of vasoconstrictor prostanoids. In endothelium-denuded coronary small arteries from normal swine, thromboxane synthase (TxS) inhibition enhanced relaxation to Up4A compared to endothelium-intact arteries, to a similar extent as P2Y12 inhibition, while the combination inhibition of P2Y12 and TxS had no additional effect. In conclusion, Up4A-induced coronary relaxation is blunted in swine with AoB, which appears to be due to the production of a vasoconstrictor prostanoid, likely thromboxane A2.
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PMID:Uridine Adenosine Tetraphosphate-Induced Coronary Relaxation Is Blunted in Swine With Pressure Overload: A Role for Vasoconstrictor Prostanoids. 2963 87


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