5‐hydroxytryptamine Induces Relaxation of Goat Pulmonary Veins: Evidence for the Noninvolvement of M and D‐tryptamine Receptors

Abstract

1 Reactivity of goat isolated pulmonary arteries and veins to a variety of vasoactive agents was investigated. 2 Bradykinin (Bk), acetylcholine (ACh), noradrenaline (NA), prostaglandin Al (PGA1), PGE2, PGF21 and histamine induced dose-dependent contractile responses on veins; 5-hydroxytryptamine (5-HT) induced veno-relaxation. Angiotensin was virtually inactive. 3 Angiotensin, NA, Bk, histamine and 5-HT produced concentration-dependent contractile responses on the arterial strips; these arteries failed to respond to ACh, PGA1, PGE2 or PGF2,. 4 The pulmonary veno-relaxant response to 5-HT was found to be resistant to propranolol, indomethacin, metiamide, cimetidine, methysergide, atropine and morphine. These findings appear to exclude the involvement of adrenergic mechanisms and prostaglandin generation as well as activation of classical M and D-tryptamine receptors by 5-HT in the goat pulmonary veins. This response may be mediated via a presynaptic inhibitory 5-HT receptor. 5 5-HT-induced arterial contractile responses were antagonized by methysergide, showing the occurrence of classical D receptors in the goat pulmonary artery. 6 It is concluded that differential reactivity of pulmonary arteries and veins to vasoactive agents may play differential role(s) in the pathophysiology inflammatory activity in goat pulmonary veins.Recently, there has been some interest in the autonomic and autacoid pulmonary pharmacology of farm animals (Eyre, 1971; 1975,a,b;Hanna & Eyre, 1978; Chand, DeRoth & Eyre, 1979;Chand & Altura, 1980). During the course of one of these investigations, 5-hydroxytryptamine (5-HT) was found to relax goat trachea (Chand et al., 1979). A preliminary study, in our laboratory, indicated that goat pulmonary veins were also relaxed by 5-HT. The pharmacological characterization of this unusual relaxant response to 5-HT on goat pulmonary veins was therefore undertaken. MethodsSeven adult goats of either sex, weighing 50 to 150 lbs, were killed by shooting and exsanguination. The lungs and heart were immediately dissected out and placed in ice-cold oxygenated Krebs-Henseleit solution. The remainder of the experimental procedures of pulmonary disease. 5-HT may exert an antiwere identical to those described earlier (Eyre, 1975,a,b; Chand et al., 1979). In brief, pulmonary veins and arteries were isolated, dissected out and cut into spiral strips. Each strip was longitudinally dissected into twin 'identical strips'. From each animal, 3 to 6 pairs of pulmonary vein strips were used within 12 to 24 h. Tissues were mounted in pairs in 15 ml isolated organ baths, containing Krebs-Henseleit solution, mixed with 95% 02 and 5% Co2 at 37'C. The composition of the Krebs-Henseleit solution was (mmol/l): NaCl 118, KCI 4.70, CaCI2 .2H20 2.5, KH2PO4 1.2, MgSO4.7H20 1.2, NaHCO3 25.0 and glucose 10.0. The strips were allowed to equilibrate for 2 h under a resting load of 2 g. Single or cumulative dose-response curves to one or two agonists were recorded with a Narco Isotonic Myograph Transducer connected to a Fisher Recor...

Effects of Mianserin, Desipramine and Maprotiline on Blood Pressure Responses Evoked by Acetylcholine, Histamine and 5‐hydroxytryptamine in Rats

“…There are experimental results suggesting that 5-HT mediates myorelaxation in certain vascular tissues (Vargaftig & Lefort, 1974;Chand, 1981). More studies appear to be required in order to clarify the physiological and pharmacological mechanisms responsible for the blood pressure-lowering effects of 5-HT in the pithed or syrosingopine pretreated rat given a small dose of a 5-HT D-receptor antagonist.…”

Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats

“…After the injection of etorphine ϩ water, Pa O 2 dropped to below 50 mmHg after 6 min. The drop following etorphine ϩ water was significant [F (10,70) A-a gradient. Figure 5 shows the effect of etorphine administration, with and without coadministration of the serotonergic ligands, on a derived variable, namely, the A-a gradient in the partial pressures of oxygen.…”

Mechanisms Involved in Serotonin-Induced Vasodilatation

“…Methysergide did not block the relaxant effects of serotonin in sheep or goat pulmo nary vein preparations [2,9], thus neither 5-HTi-like nor 5-HT2 receptors appear to be present in these tissues. Nevertheless, in all the other in vitro preparations tested (cat cranial artery, cat saphenous vein, rabbit ju gular vein and pig vena cava), methysergide blocked the vascular smooth muscle relaxant effects of serotonin or 5-CT at concentra tions consistent with an action at 5-HT 1-like receptors [8,10,12,14,15,21], although blockade was competitive only in the cat saphenous vein and pig vena cava prepara tions.…”

“…Serotonin-induced vascular smooth mus cle relaxation was first demonstrated in sheep pulmonary artery preparations [2], Subsequent studies have demonstrated this action in cat and human cranial arteries [8], goat pulmonary vein [9], cat saphenous vein [10], pig vena cava [11], and rabbit jugular vein [ 12]. All of these tissues except goat pul monary vein required prior contraction to allow manifestation of the relaxant response to serotonin.…”