Inhibitory effects of glyceryl trinitrate on alpha‐adrenoceptor mediated contraction in the human internal mammary artery.

Abstract

1. Sympathomimetic amines have been considered to be related to vasospasm. Previous studies showed that the human internal mammary artery (IMA) was capable of weak beta‐adrenoceptor mediated relaxation and that alpha‐adrenoceptor agonists may induce contraction in the human IMA. 2. We investigated the effects of glyceryl trinitrate (GTN), a vasodilator agent often used perioperatively, on alpha‐adrenoceptor mediated contraction in the human IMA. 3. Discarded human IMA segments were taken from 37 patients who underwent IMA‐coronary artery bypass graft operations and equilibrated in an organ bath. 4. A specially designed technique was used to normalize the vessel segments under the pressure similar to the in vivo situation. Noradrenaline (NA), phenylephrine (PE), and methoxamine (MO) were used to contract the vessel segments. 5. GTN fully relaxed PE or MO (submaximal concentration) induced precontraction. Therapeutic plasma concentration of GTN relaxed 40‐90% of the PE induced contraction (2.82 g, EC50 = 7.92 +/‐ 0.06 ‐log M) and 20‐90% of the MO induced contraction (1.8 g, EC50 = 7.63 +/‐ 0.16 ‐log M). Pretreatment by the therapeutic plasma concentration of GTN inhibited the contraction induced by NA, PE in a different range. It reduced the NA induced contraction (6.9 g) by 14.8‐ 38% (P greater than 0.05) and the PE induced contraction (4.3 g) by 7.9‐ 39.3% (P greater than 0.05). The alpha 1‐adrenoceptor antagonist prazosin, at the therapeutic plasma concentration, nearly totally abolished the NA or PE induced contraction (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…On the other hand, the present study demonstrates that the ET-1-induced contraction is not fully reversed by GTN in the human IMA indicated by the fact that the maximal relaxation was 76.44%. In contrast, GTN has been demonstrated to reverse completely the contraction induced by U46619 [7] or a-adrenoceptor agonists [20]. This observation is partially in accordance with others [30].…”

“…In the previous studies [7,20], we have observed that although GTN is a potent vasodilator in reversing contraction induced by a number of vasoconstrictors such as the thromboxane A2 mimetic U46619 [7] and a-adrenoceptor agonists [20], it is less effective in the human IMA if applied to prevent the contraction induced by these constrictors although the mechanism is unclear. In this study, we continuously observed this phenomenon.…”

“…These four rings were equilibrated for 5 min [7,20] with vehicle of GTN (0.1% ethanol) or 10 nM, 100 nm, or 30 gM GTN. Those concentrations (10-100 nM) were chosen since they are similar to the optimal plasma concentration reached clinically [22,23] and the supra-clinical concentration (30 gM) was given to study the possible maximal inhibitory effect.…”

“…These four rings were equilibrated for 25 min [7] with vehicle of nifedipine (1% ethanol) or 20 nM, 200 nm, or 30 gM nifedipine. In these concentrations, 20 and 200 nm are relevant to the optimal plasma concentrations reached clinically [24]. A cumulative concentration-contraction curve was then constructed for ET-1.…”

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

“…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.…”