Muhammad Arshad, MD, Venkataramana Vijay, MD, Beverly C

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Thromboxane Receptor Stimulation Suppresses Guanylate Cyclase-Mediated Relaxation of Radial Arteries Muhammad Arshad, MD, Venkataramana Vijay, MD, Beverly C. Floyd, MS, MPH, Brian Marks, BS, Mohan R. Sarabu, MD, Michael S. Wolin, PhD, Sachin A. Gupte, MD, PhD The Annals of Thoracic Surgery Volume 81, Issue 6, Pages 2147-2154 (June 2006) DOI: 10.1016/j.athoracsur.2006.01.024 Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Contraction of the internal mammary artery (IMA) and the radial artery (RA) evoked by KCl, U46619, norepinephrine (NE) and phenylephrine (Phen). (A) High (123 mM) and low (30 mM) KCl elicited force in the IMA (n = 30) and the RA (n = 10). In both (B) the IMA (n = 15 to 20) and (C) the RA (n = 8 to 10), U46619 was a more potent vasoconstrictor than either Phen or NE. Note error bars are small and they overlap with symbols. The Annals of Thoracic Surgery 2006 81, 2147-2154DOI: (10.1016/j.athoracsur.2006.01.024) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Comparison of contractions evoked in the internal mammary artery (IMA) and the radial artery (RA) by KCl, U46619, and phenylephrine. There were no significant differences in the force generated (A) by 30 mM KCl or (B) by U46619 in the IMA (n = 15 and n = 30, respectively) and in the RA (n = 10 and n = 8, respectively). (C) Phenylephrine-induced contractions were significantly stronger in the IMA (n = 20) than in the RA (n = 10). The Annals of Thoracic Surgery 2006 81, 2147-2154DOI: (10.1016/j.athoracsur.2006.01.024) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Basal thromboxane A2 (TxA2) to prostacyclin (PGI2) ratios in the IMA (n = 6) and in the RA (n = 6). Estimated were levels of vasoconstrictor TxA2 (TxB2) and Keto PGF2α, the stable metabolites of TxA2 and PGI2, respectively. (IMA = internal mammary artery; RA = radial artery.) The Annals of Thoracic Surgery 2006 81, 2147-2154DOI: (10.1016/j.athoracsur.2006.01.024) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Effects of the L-type Ca2+ channel inhibitor nifedipine on internal mammary artery (IMA) and radial artery (RA) contraction. Nifedipine dose-dependently relaxed (A) IMA (n = 15) and (B) RA (n = 5) precontracted with phenylephrine or U46619. Note error bars are small and they overlap with symbols. (Phen = phenylephrine.) The Annals of Thoracic Surgery 2006 81, 2147-2154DOI: (10.1016/j.athoracsur.2006.01.024) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 5 Effects of acetylcholine and nitroglycerin on internal mammary artery (IMA) and radial artery (RA) contraction. (A, C) Acetylcholine or (B, D) nitroglycerin dose-dependently relaxed IMA (n = 20 each) and RA (n = 10 each) precontracted with either phenylephrine (Phen) or U46619. Note that both acetylcholine and nitroglycerine were significantly less effective at relaxing RA precontracted with U46619 than phenylephrine. The Annals of Thoracic Surgery 2006 81, 2147-2154DOI: (10.1016/j.athoracsur.2006.01.024) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 6 Estimation of soluble guanylate cyclase (sGC) activity and protein in the internal mammary artery (IMA) and the radial artery (RA). The soluble guanylate cyclase (sGC) activity measured by estimating guanosine 3’,5’-cyclic monophosphate (cGMP) levels was increased in the IMA (n = 6) and RA (n = 6) pretreated with nitroglycerin (NTG). The U46619 reduced NTG-induced sGC activity in the RA. The lower panel shows that levels of the sGC protein were similar in the IMA and the RA. (IB = immunoblotted; KD = kilodalton.) The Annals of Thoracic Surgery 2006 81, 2147-2154DOI: (10.1016/j.athoracsur.2006.01.024) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions