Sympathy for the devil: the role of thromboxane in the regulation of vascular tone and blood pressure

Abstract

Historically, the vasodilatory prostanoids, especially prostacyclin and prostaglandin E(2), are believed to contribute significantly to the regulation of normal vascular tone and blood pressure (BP), primarily by counteracting the prevailing effects of the systemic vasoconstrictor systems, including angiotensin II, the catecholamines, and vasopressin. In contrast, the primary vasoconstrictor prostanoid thromboxane A(2) (TxA(2)) is produced in far smaller quantities in the normal state. While TxA(2) is believed to play a significant role in a variety of cardiovascular diseases, such as myocardial infarction, cerebral vasospasm, hypertension, preeclampsia, and various thrombotic disorders, its role in the regulation of vascular tone and BP in the normal physiological state is, at best, uncertain. Numerous studies have firmly established the dogma that TxA(2), while important in pathophysiological states in males, plays little or no role in the regulation of vascular tone or BP in females, except in the pulmonary vasculature. However, this concept is largely based on the predominant and preferential use of males in animal and human studies. Recent studies from our laboratory and others challenge this dogma and reveal that the TxA(2) pathway in the systemic vascular wall is an estrogen-dependent mechanism that appears to play an important role in the regulation of vascular tone and BP in females, in both normal and pathophysiological states. It is proposed that the potent vasoconstrictor action of TxA(2) is beneficial in the female in the normal state by acting as a local counterregulatory mechanism to increase vascular tone and BP and defend against hypotension that could result from the multiple estrogen-sensitive local vasodilator mechanisms present in the female vascular wall. Validation of this proposal must await further studies at the systemic, tissue, and molecular levels.

Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-α

“…TXA2 is produced primarily by platelets, but there is evidence of the synthesis of the vasoconstrictor metabolite by the endothelium (Sellers & Stallone 2008). E 2 did not change TXA2 production in our experiments.…”

Beneficial Effect of Propofol on Arterial Adenosine Triphosphate-sensitive K+Channel Function Impaired by Thromboxane

“…Under this anesthetic condition, the rats were killed by exsanguination, and thoracic aortas were harvested. Thoracic aortic rings of 2.5 mm in length were studied in modified Krebs-Ringer's bicarbonate solution (control solution) of the following composition (in mM): NaCl 119, KCl 4.7, CaCl 2 2.5, MgSO 4 1.17, KH 2 PO 4 1.18, NaHCO 3 25, and glucose 5.5. Endothelial cells were removed mechanically by gentle rubbing of the lumen using a small forceps to avoid the modification mediated by endothelium-derived vasodilator substances as well as endothelial ATP-sensitive K ϩ channels.…”

“…1,2 Studies in cultured cells from pulmonary arterial endothelium and corpus cavernosum demonstrated that thromboxane A 2 , which is known as an eicosanoid derived from cyclooxygenase, increases superoxide production via the activation of NADPH oxidase. [3][4][5][6] However, it is still unclear whether thromboxane A 2 augments this enzymatic activity in the intact artery. Accumulating findings demonstrated that adenosine triphosphate (ATP)-sensitive K ϩ channels make significant contributions in the regulation of vascular smooth muscle tone under normal physiologic as well as pathophysiological conditions, 7 whereas increased oxidative stress reportedly induces malfunction of these channels.…”

Estradiol Regulation of Prostanoids Production in Endothelium

“…As platelets are anucleate, there can be no induction of COX-2 enzyme synthesis (Patrignani et al, 1999). Thromboxane A 2 can also be synthesized from endothelial cells (Sellers & Stallone, 2008). The third possibility is a transcellular formation of thromboxane A 2 by platelets from prostaglandin H 2 released by endothelial cells (Camacho & Vila, 2000).…”