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 microM indomethacin) and the thromboxane A(2) (TxA)(2) receptor [1 microM [1S-[1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[2-(phenylamino)carbonyl]hydrazine]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (SQ-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 calcium-reuptake 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 BQ-123 [cyclo(l-Leu-d-Trp-d-Asp-l-Pro-d-Val)]. Thus, hypoxia relaxes IMA and RA by a prostaglandin-independent mechanism potentially involving enhanced intracellular calcium reuptake. The prostaglandin-mediated alterations of responses to hypoxia-reoxygenation seen in IMA, but not in RA, may predispose IMA to vasospasm-related complications of CABG.

• Authors: Sachin A Gupte, Elias A Zias, Mohan R Sarabu, Michael S Wolin
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 311 Issue 2 Pg. 510-8 (Nov 2004) ISSN: 0022-3565 [Print] United States
• PMID: 15229231 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-Agonists
• Endothelin Receptor Antagonists
• Potassium Channel Blockers
• Prostaglandin Antagonists
• Prostaglandins
• Thromboxane A2
• Epoprostenol
• Protein Kinase C
• Oxygen
• Calcium

Topics

• Adrenergic alpha-Agonists (pharmacology)
• Calcium (metabolism)
• Endothelin Receptor Antagonists
• Epoprostenol (biosynthesis)
• Humans
• Hypoxia (metabolism)
• In Vitro Techniques
• Mammary Glands, Human (anatomy & histology, drug effects)
• Oxygen (metabolism)
• Potassium Channel Blockers (pharmacology)
• Prostaglandin Antagonists (pharmacology)
• Prostaglandins (biosynthesis)
• Protein Kinase C (metabolism)
• Radial Artery (drug effects, physiology)
• Thromboxane A2 (biosynthesis)
• Vasodilation (drug effects, physiology)