Role of Prostaglandins in Mediating Differences in Human Internal Mammary and Radial Artery Relaxation Elicited by Hypoxia

Abstract

The effects of hypoxia-reoxygenation on internal mammary (IMA) and radial (RA) arteries used for coronary artery bypass grafting (CABG) were examined to identify mechanisms regulating contractile function and differences that could contribute to vasospasm. Isolated endothelium-intact IMA and RA rings precontracted with KCl (30 mM) rapidly dilated to hypoxia (95% N 2 /5% CO 2 ) with a greater relaxation in RA than IMA. Inhibitors of cyclooxygenase (10 M indomethacin) and the thromboxane A 2 (TxA 2 ) -29548)] potentiated the relaxation to hypoxia in IMA, but not RA, a response associated with increases in TxA 2 . Relaxation of IMA and RA to hypoxia appears to involve a calciumreuptake mechanism inhibited by cyclopiazonic acid (0.2 mM), and it was not attenuated by a blocker of potassium channels (10 mM TEA). The recovery of force generation of IMA, but not RA, upon reoxygenation after 30 min of hypoxia was significantly reduced in the initial phase of reoxygenation by indomethacin and SQ-29548 and by endothelin receptor blocker. Thus, hypoxia relaxes IMA and RA by a postaglandin-independent mechanism potentially involving enhanced intracellular calcium reuptake. The prostaglandinmediated alterations of responses to hypoxia-reoxygenation seen in IMA, but not in RA, may predispose IMA to vasospasm-related complications of CABG.

Glc-6-PD and PKG contribute to hypoxia-induced decrease in smooth muscle cell contractile phenotype proteins in pulmonary artery

“…Frozen sections of pulmonary artery were fixed in acetone, and antigen retrieval was done with 0.1% Triton X-100 as described previously (14,15,22). After the sections were blocked by incubation for 1 h in 5% normal goat serum or 5% BSA at room temperature, they were incubated with primary antibody overnight at 4°C.…”

Relationships Between Vascular Oxygen Sensing Mechanisms and Hypertensive Disease Processes

“…[12,13,18] Since the biosynthesis of some autacoids including nitric oxide, prostaglandins, cytochrome P450-derived eicosanoids and ROS are oxygen-dependent, these mediators often influence or modulate systemic and pulmonary responses to hypoxia. [20–22]…”

Pharmacology of Arterial Grafts for Coronary Artery Bypass Surgery

“…Additionally, it was previously reported that RA grafts are more sensitive to TxA 2 [13]. Furthermore, it has been reported that IMAs produce substantial amounts of both PGI 2 and TxA 2 [128]; nonetheless, the TxA 2 to PGI 2 ratio was significantly higher in the RA than in the IMA. Because PGI 2 antagonizes the actions of TxA 2 , the higher TxA 2 to PGI 2 ratio implies that TxA 2 would exert greater effects in the RA.…”