Thromboxane receptor stimulation suppresses guanylate cyclase-mediated relaxation of radial arteries.
BACKGROUND
The internal mammary artery (IMA) and the radial artery (RA) are routinely used in coronary artery bypass grafting. However, RA grafts have a higher incidence of postoperative vasospasm and comparatively poor patency rates. The present study was undertaken to investigate the signaling pathways mediating contraction and relaxation in the IMA and RA with the aim of better understanding the mechanism underlying the propensity of RA grafts to spasm.


METHODS
We examined the contractile responses of the IMA and RA to KCl (a depolarizing agent), phenylephrine (an alpha-adrenergic agonist), and U46619 (a thromboxane analogue).


RESULTS
Contractions induced by KCl or U46619 did not significantly differ in IMA and RA. By contrast, phenylephrine evoked significantly greater contraction of the IMA than the RA. Contractions induced by both phenylephrine and U46619 were dose-dependently inhibited by nifedipine (an L-type calcium channel blocker). Estimation of thromboxane A2 (TxA2) and prostacyclin (PGI2) synthesis revealed that the TxA2 to PGI2 ratio in the RA was twice that in the IMA. Moreover, acetylcholine-induced and nitroglycerin-induced relaxation of RA precontracted with U46619 was significantly impaired, as compared with RA precontracted with phenylephrine. These data suggest that inhibition of nitroglycerin-induced soluble guanylate cyclase activity by U46619 was at least partially responsible for the diminished vasodilatory response of RA to nitric oxide.


CONCLUSIONS
Our findings suggest that by reducing nitric oxide-stimulated soluble guanylate cyclase activity, the higher TxA2 to PGI2 ratios in RA, and the elevated serum TxA2 levels seen during coronary artery bypass grafting operations, may underlie the vasospasm and poor patency rates seen with the RA.
Arshad
Muhammad
M
Department of Physiology, New York Medical College, Westchester Medical Center, Valhalla, New York, USA.
Vijay
Venkataramana
V
Floyd
Beverly C
BC
Marks
Brian
B
Sarabu
Mohan R
MR
Wolin
Michael S
MS
Gupte
Sachin A
SA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D001026:Coronary Artery Bypass / Q000379:methods*; D011464:Epoprostenol / Q000096:biosynthesis; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D007387:Internal Mammary-Coronary Artery Anastomosis; D007537:Isometric Contraction / Q000187:drug effects; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009928:Organ Specificity; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017534:Radial Artery / Q000187:drug effects / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000502:physiology*; D017482:Receptors, Thromboxane / Q000819:agonists* / Q000502:physiology; D000071756:Soluble Guanylyl Cyclase; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000097:blood; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D018160:Receptors, Cytoplasmic and Nuclear; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D005576:Colforsin; D010656:Phenylephrine; D009569:Nitric Oxide; D013928:Thromboxane A2; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D005996:Nitroglycerin; D009543:Nifedipine; D000109:Acetylcholine; D009638:Norepinephrine