Regulation of Human Internal Mammary and Radial Artery Contraction by Extracellular and Intracellular Calcium Channels and Cyclic Adenosine 3', 5' Monophosphate

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Abstract

Background

The internal mammary (IMA) and radial arteries (RA), which are routinely used in coronary artery bypass grafting, show a significant incidence of postoperative vasospasm. The present study evaluated the respective roles of calcium (Ca2+)-dependent and cyclic adenosine 3', 5' monophosphate-dependent (cAMP) signaling in mediating contraction and relaxation of the IMA and RA.

Methods

We examined the contractile responses of the IMA and RA to potassium chloride, a depolarizing agent; phenylephrine, an α-adrenergic agonist; and U46619, a thromboxane analogue, in the absence and presence (0.045 to 1.500 mM) of extracellular Ca2+.

Results

Potassium chloride elicited little or no contraction in the absence of extracellular Ca2+. Contractions elicited by U46619 were similar in the IMA and RA, both in the absence and presence of extracellular Ca2+. By contrast, phenylephrine elicited significantly greater extracellular Ca2+-dependent contraction of the IMA than the RA. Estimation of cyclic guanosine 3', 5' monophosphate (cGMP) and cAMP revealed levels of cAMP to be about fourfold higher than cGMP in both the RA and IMA. Whereas forskolin and milrinone elicited similar relaxation of IMA and RA precontracted with either U46619 or phenylephrine and increased adenylate cyclase-catalyzed cAMP production, isoproterenol-induced relaxation of the arteries precontracted with U46619 was significantly impaired compared with arteries precontracted with phenylephrine.

Conclusions

Our findings suggest that thromboxane A2 receptor-dependent pathways activate contraction of IMA and RA through both extracellular Ca2+-dependent and Ca2+-independent pathways. In addition, adenylate cyclase appears to play a key role in attenuating thromboxane A2 and α-adrenergic receptor-mediated contraction through both pathways.

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