Interaction between endothelin and vasodilators in the human internal mammary artery.

Abstract

1. The internal mammary artery (IMA) is the primary choice as an arterial graft for coronary artery bypass surgery. Endothelin (ET) has been recently measured with an increased release after cardiopulmonary bypass for coronary artery bypass grafting. Threshold concentrations of ET‐1 have been found to amplify specifically contractions induced by noradrenaline and serotonin. This study was designed to investigate the effect of glyceryl trinitrate (GTN) and calcium antagonists on ET‐1 contraction in the human IMA. 2. Human IMA segments taken from 21 patients undergoing IMA‐coronary artery bypass grafting were mounted in an organ bath under the physiological pressure determined from their own length‐tension curves. Four ring segments were allocated into four groups. One served as a control and the others were treated with GTN (10, 100 nM, or 30 microM) for 5 min or nifedipine (20 or 200 nM, or 30 microM) for 25 min before concentration‐contraction curves to ET‐1 were established. In separate experiments, the concentration‐relaxation curves to GTN or nifedipine were established in the IMA rings precontracted with ET‐1 (10 nM). 3. Pretreatment of IMA with GTN for 5 min did not alter the ET‐1‐induced contraction. Pretreatment with 20 or 200 nM of nifedipine slightly but not significantly, altered the maximum contraction induced by ET‐1. Higher concentrations (30 microM) significantly reduced the maximum contraction force (P = 0.008). On the other hand, GTN caused 76.44 +/‐ 6.35% relaxation in ET‐1‐precontracted IMA. In contrast, the nifedipine‐induced relaxation was difficult to establish due to unsustained contraction to ET‐1.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential greater than additive vasorelaxant actions of milrinone and nitroglycerin on human conduit arteries

“…The human IMA has been demonstrated as an active artery that responds to many vasoconstrictors [l5, 18,19,231. In the present study, the depolarizing agent K" and TXA, mimetic U46619, a vasoconstrictor measured with increased plasma concentrations during cardiopulmonary bypass [34], have been used to contract the artery.…”

“…However, relaxation of smooth muscle that involves reversal of a latch state is less dependent on the inhibition of Ca2 + mobilization or on dephosphorylation of myosin [37,381. Another possible explanation is rapid tolerance to NTG as described previously [ 18).…”

“…Any discarded distal IMA segments were collected and placed in a container with oxygenated, physiological solution (Krebs') maintained at 4"C, and then transferred to the laboratory. The details of collecting, dissecting, and mounting of the IMA rings and the organ bath technique have been described previously [14][15][16][17][18][19]. Briefly, the rings were stretched-up in progressive steps to determine the length-tension curve for each ring.…”

Pharmacology of Arterial Grafts for Coronary Artery Bypass Surgery

“…These drugs are effective against a range of constrictor stimuli and they are widely used in CABG patients. Nitrovasodilators have been shown to be potent vasodilators in the human IMA [55,61,[74][75][76][77][78][79]. It has been demonstrated that NTG is compares favorably with diltiazem in the prevention of IMA spasm [80] and it is effective for either topical, intraluminal, or systemic use [78,81,82].…”

“…However, rapid tolerance (tachyphylaxis) of vessels develops to nitrovasodilators. Therefore, they are less potent in the prevention of vasospasm [54,74,75,83]. NTG is more potent in its vasorelaxing effect when it is compared to SNP.…”