Effects of trimetaquinol on equine pulmonary vascular and airway smooth muscle.

Abstract: Trimetaquinol [TMQ: 1-(3’,4‘,5’-trimethoxybenzyl)6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride] a potential p-sympathomimetic bronchodilator (Iwasawa & Kiyomoto 1967), has been shown to be an effective tracheal smooth muscle relaxant in guineapigs (Iwasawa & Kiyomoto 1967; Brittain 1972; Brittain et a1 1970, 1976) and an inhibitor of experimental bronchospasm in guinea-pigs and cats (Brittain et a1 1970; Brittain 1972). In addition, clinical studies with TMQ indicated that the drug was an effective bronchodilator in mild to moderate asthma (Yamamura & Kishimoto 1968). It may be of value to determine the in vitro effects of bronchodilators on pulmonary vascular smooth muscle as well as airways (Hanna & Eyre 1979), since it is possible that, in vivo, inhaled bronchodilators may be distributed to the pulmonary vasculature, altering the vessel smooth muscle tone and consequently the pulmonary blood flow. This consideration plus the fact that TMQ has a non-selective 8-adrenergic action and some papaverine-like characteristics (Sato et a1 1967; Brittain 1972; Brittain et a1 1970, 1976) prompted these preliminary investigations of the action of TMQ on an integrated airway and a pulmonary vascular smooth muscle system from horse. Tissues from horse lung were employed because of the size of the pulmonary system, and the reported similarity of equine and human lung at the subgross and gross anatomical levels (McLaughlin et a1 1961; Tyler et al 1971). Pulmonary venous and tracheal smooth muscle was obtained from normal horses freshly killed in a local abattoir. Tissues were prepared according to the methods previously outlined (Hanna & Eyre 1978, 1979) and suspended in 10 and 20 ml organ baths with Webs-Henseleit solution aerated with 95 % 0 2 / 5 % CO, at 37 “C. The relaxant effects of TMQ were measured (isotonically) by first contracting the vein with an ED50 concentration of histamine (8.0 x M) and then adding increasing concentrations of TMQ in a cumulative fashion after the contractile response had reached maximum, Relaxation responses were expressed as percent inhibition of the histamine ED50 contraction. For tracheal studies, the relaxant effects of TMQ were measured (isometrically) by first pre-incubating the tissues with single concentrations of TMQ for 6 min, then challenging the tissues with an ED50 concentration of carbachol (5.0 x M).