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W A Bax

Publications and source records attributed to W A Bax.

30 records · Page 2Linked to original sources

Heterogeneity of endothelin/sarafotoxin receptors mediating contraction of the human isolated saphenous vein.

We investigated the effect of the ETA receptor antagonist, BQ-123 (0.1 and 1 microM), on contraction of the human isolated saphenous vein induced by endothelin-1 or sarafotoxin S6b. Contraction in response to endothelin-1 was not affected by BQ-123. In contrast, BQ-123 biphasically attenuated the contractions due to sarafotoxin S6b. These data indicate that (i) endothelin-1 induces contractions of the human saphenous vein via a non-ETA receptor and (ii) contractions in response to sarafotoxin S6b are mediated in part via a receptor different from the receptor mediating contraction due to endothelin-1.

Aged↗

5-Hydroxytryptamine stimulates human isolated atrium but not ventricle.

Although 5-hydroxytryptamine (5-HT) elicits positive inotropic effects in the human isolated atrium via 5-HT4 receptors, no data are available about its effects in the ventricular myocardium. We investigated the inotropic effects of 5-HT in human healthy ventricular trabeculae and compared these effects with those in right atrial trabeculae. Baseline force of contraction as well as the response to noradrenaline, used to check inotropic responsiveness of the tissue, was significantly higher in ventricular (391 +/- 10 and 719 +/- 126 mg, respectively) than in atrial tissue (189 +/- 5 and 383 +/- 79 mg, respectively). However, 5-HT increased the force of contraction up to 309 +/- 82 mg at 10(-4) M in atrial trabeculae, but failed to affect the force of contraction in ventricular tissue. We conclude that, in contrast to atrial tissue, 5-HT is ineffective as a positive inotropic agent in human ventricular trabeculae. This finding obviously rules out the development of 5-HT4 receptor agonists for the treatment of heart failure, but suggests the absence of ventricular side-effects of 5-HT4 receptor (ant)agonists should these agents be used in the treatment of gastrointestinal disorders.

Heart Atria↗

Endothelin receptors in the human coronary artery, ventricle and atrium. A quantitative autoradiographic analysis.

In the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. Displacement of [125I]Sf6b (Sarafotoxin S6b) (30 pM)- and [125I]ET-1 (30 pM)-labeled binding sites was studied using ET-1, the ETA receptor selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp-]), and the ETB receptor selective ligand [Ala1, 3, 11, 15]ET-1. Specific binding was more dense in atrium and coronary artery (relative optical density (r.o.d.): 0.14 +/- 0.01 and 0.16 +/- 0.01, respectively) than in ventricular muscle (r.o.d.: 0.10 +/- 0.01). In the coronary artery, binding was especially dense in the media. ET-1 displaced [125I]ET-1 and [125I]Sf6b monophasically in atrium, ventricle and coronary artery. [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1 and [125I]Sf6b-labeled sites biphasically in the ventricle and in the atrium. In the human coronary artery, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1-labeled sites monophasically (pIC50: ET-1 (9.72 +/- 0.12) > BQ-123 (6.84 +/- 0.08) > [Ala1,3,11,15]ET-1 (6.40 +/- 0.12). In contrast, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]Sf6b-labeled coronary artery sites biphasically (high affinity pIC50: BQ-123, 9.03 +/- 0.25; [Ala1,3,11,15]ET-1, 8.40 +/- 0.14; low affinity pIC50: BQ-123, 7.24 +/- 0.14; [Ala1,3,11,15]ET-1, 6.99 +/- 0.09). These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

5-Hydroxytryptamine-induced contractions of the human isolated saphenous vein: involvement of 5-HT2 and 5-HT1D-like receptors, and a comparison with grafted veins.

The receptors mediating the contractile effect of 5-hydroxytryptamine (5-HT) on the human isolated saphenous vein, obtained from 42 patients undergoing coronary bypass surgery, have been further characterized using a number of 5-HT-related drugs. The rank order of agonist potency was 5-carboxamidotryptamine (5-CT) approximately 5-HT greater than methysergide approximately sumatriptan approximately alpha-methyl-5-HT approximately 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indolesuccinate (RU 24969) approximately 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) greater than 2-methyl-5-HT greater than 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT). Flesinoxan was inactive as an agonist. Ketanserin (1 mumol/l) hardly affected sumatriptan-induced contractions but it caused a rightward shift of the upper part of the concentration-response curve of 5-HT and 5-CT. The same concentration of ketanserin caused a parallel rightward shift of the concentration-response curves of alpha-methyl-5-HT and DOI with pKB values of 7.1 and 7.1, respectively. The responses to sumatriptan were antagonized by methiothepin (0.1 mumol/l), metergoline (0.1 and 1 mumol/l), rauwolscine (1 mumol/l) and cyanopindolol (1 mumol/l); the calculated pKB values were 7.3, 6.9, 7.3, 6.7 and 6.5, respectively. Contractions to 5-HT were antagonized by methysergide (1 mumol/l), methiothepin (0.1 mumol/l; pKB = 7.1), ICS 205-930 (1 mumol/l; pKB = 5.9) and flesinoxan (30 mumol/l; pKB = 5.3). Remarkably, the contractions elicited by 2-methyl-5-HT were not attenuated by ICS 205-930, but were antagonized by methiothepin (0.1 mumol/l) and, more markedly, by ketanserin (1 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗

5-Hydroxytryptamine increases contractile force in porcine right atrium but not in left ventricle.

Positive chronotropic as well as inotropic effects of 5-hydroxytryptamine (5-HT) have been observed in pig atrial tissue, but no data are available about the direct effects of 5-HT on ventricular tissue. In the present study we investigated inotropic effects of 5-HT on atrial and ventricular trabeculae obtained from hearts of 3 months old pigs. The baseline isometric contractile force was significantly higher in ventricular (4.14 +/- 1.25 mN) than in atrial tissue (0.47 +/- 0.11 mN). A noradrenaline concentration-response curve (0.01 to 10 mumol/l) was used to check contractile responsiveness of the tissue and all responses were expressed as percentage of the response to 10 mumol/l noradrenaline. Noradrenaline caused a concentration-dependent increase in contractile force in both atrial and ventricular trabeculae. In contrast, though 5-HT (0.01 to 100 mumol/l) did increase force of contraction in atrial tissue (maximum: 72 +/- 20% of the response to noradrenaline 10 mumol/l), the contractility of ventricular trabeculae was not significantly affected (maximum: 12 +/- 6%). The present data show that, in contrast to atrial tissue, contractile force of ventricular tissue could not be significantly affected by 5-HT. To our knowledge, this is the first study to show that an agent which increased force of contraction in the atrium, did not have a corresponding effect on the ventricle. These findings may have important implications for a better understanding of the physiology and pharmacology of cardiac contractility.

Animals↗

The influence of the mode of treatment of zygomatic bone fractures on the healing process of the infraorbital nerve.

Several authors have described the influence of the method of treatment of a fracture of the zygomatic complex on the recovery of the infraorbital nerve. In this study, the results of treatment of 106 patients with an isolated, non-comminuted, unstable fracture of the zygomatic bone are presented. Thirty-eight patients underwent fixation with interosseous wiring and 68 patients were treated with a miniplate osteosynthesis across the frontozygomatic suture. In the group with wire fixation, 50% suffered persistent reduced sensitivity in the infraorbital region at follow-up examination, whereas in the group with a miniplate osteosynthesis only 22.1% had persistent neurological sequelae. On the basis of these findings we recommend a miniplate osteosynthesis in all unstable zygomatic bone fractures with displacement.

Bone Plates↗