Release of prostaglandin E-like material from perfused mesenteric blood vessels of rabbits.

Infusions of noradrenaline (1-3 mug ml(-1) min(-1)) into the mesenteric vascular preparation of the rabbit caused a 2 to 5 fold rise in perfusion pressure and a release of prostaglandin E-like material (3.23 +/- 0.65 (s.e.) ng PGE2 equivalents ml(-1)). Indomethacin (3 mug ml(-1)) prevented whereas arachidonic acid (0.2 mug ml(-1)) augmented, the noradrenaline-evoked release of a prostaglandin E-like material. The walls of arterioles or precapillary vessels are the proposed site of prostaglandin generation.     

Antigen-induced contraction of guinea-pig trachea: search for mediator release with cascade superfusion bioassay.

Ovalbumin induces contraction of sensitized guinea-pig trachea, both in the presence and absence of indomethacin. Cascade superfusion bioassay was employed to detect mediator release. A prostaglandin E-like material was released in response to antigen in the absence of indomethacin but, no biologically active material could be detected from trachea in the presence of indomethacin. Thus the substance responsible for antigen-induced tracheal contraction, although appearing to be a lipoxygenase product, is as yet undefined.     

Inhibition by cromoglycate of histamine release from rat peritoneal mast cells induced by mixtures of dextran, phosphatidyl serine and calcium ions

1 Dextran releases histamine from rat peritoneal mast cells in the presence but not in the absence of phosphatidyl serine (PS). With PS (10 mug/ml) present the effect of dextran was concentration-dependent in the range of 0.2-6 mg/ml.2 PS releases little histamine on its own but mixed with dextran (6 mg/ml) produces a graded effect in the range of 0.3-10 mug/ml.3 The combination of dextran and PS releases no histamine in a medium containing less than 0.1 mM calcium. As the calcium concentration is increased, release occurs and a maximum is reached at calcium 1 mM; at higher concentrations release falls off sharply.4 Histamine release by the combination of dextran (6 mg/ml), PS (10 mug/ml) and calcium (1.8 mM) is inhibited by cromoglycate in the same range (1-30 muM) that inhibits anaphylactic histamine release from rat peritoneal cells.5 Inhibition by cromoglycate occurred with all dextran concentrations tested (0.2-15 mg/ml) but high concentrations of PS (30 and 100 mug/ml) overcame the effect of cromoglycate (2 and 10 muM). Calcium concentrations above 1 mM augmented inhibition by cromoglycate 2 and 10 muM.     

The effect of angiotensin I converting enzyme inhibitor (SQ 20881) on the release of prostaglandins by rabbit kidney, in vivo.

1. Prostaglandin E- and F-like material has been estimated in renal venous blood of the left kidney of anaesthetized rabbits following renal nerve section. Prostaglandins were estimated by bioassay following solvent extraction and column chromatography. 2. Electrical stimulation of the renal nerves of the left kidney to reduce renal blood flow by approximately 15% for 15 min resulted in a significant increase in the concentration of prostaglandin E-like material in the renal venous blood. The peak values were normally seen either in the last 5 min of the stimulation period or in the first 5 min after the end of the stimulation period. The concentration of prostaglandin F-like material was not significantly altered. 3. Similar reduction of renal blood flow of the left kidney by renal artery constriction also resulted in a significant increase in the concentration of prostaglandin E- but not F-like material in renal venous blood. The timing and magnitude of the response was comparable with that observed with renal nerve stimuation. 4. The effect of an angiotensin I converting enzyme inhibitor, SQ 20881, on the response to both renal nerve stimulation and renal artery constriction has been studied. The administration of the drug did not significantly reduce the release of prostaglandins from the denervated kidneys, however, the increase in prostaglandin E-like material, in response to both stimuli, was abolished. 5. The results suggest that the increase in prostaglandin E-like material released from the kidney in response to low frequency stimulation or to modest reductions in renal blood flow is dependent on the release of renin and that the effect is mediated by the formation of angiotensin II and not angiotensin I.     

Possible influence of intrarenal generation of kinins on prostaglandin release from the rabbit perfused kidney.

The effects of bradykinin and kininogen on renal prostaglandin release were studied in rabbit isolated kidneys perfused with oxygenated Krebs solution. The concentration of prostaglandin-like material in kidney effluent was determined by bioassay after extraction of the samples with organic solvents. In 7 experiments the samples were assayed after separation of prostaglandins E and F by thin layer chromatography. Addition of bradykinin to the perfusing fluid increased the venous and urinary effluxes of prostaglandin E-like substance by sixfold and fivefold, respectively, but efflux of prostaglandin F-like material was unaffected. Addition of kininogen to the perfusing fluid augmented the venous and urinary release of prostaglandin E-like substances by fifteenfold and ninefold respectively and caused a twofold increase in the efflux of prostaglandin F-like material into the venous effluent. Aprotinin, a kallikrein inhibitor, reduced the prostaglandin releasing action of kininogen but not of bradykinin. In contrast, inhibition of prostaglandin synthesis by indomethacin suppressed the release of prostaglandin evoked by either bradykinin or kininogen. This study suggests that augmented release of prostaglandins in response to kininogen is a consequence of renal generation of kinins. Thus, changes in the intrarenal activity of the kallikreinkinin system may modulate renal prostaglandin release.     

Inhibition of peristalsis in guinea-pig isolated ileum and colon by drugs that block prostaglandin synthesis.

1 Methods of analysing peristaltic activity have been evaluated by the use of recordings of longitudinal and circular muscle activity and of propulsion in whole segments of guinea-pig ileum and colon. 2 Some prostaglandin synthesis inhibitors, and antagonists of prostaglandin action were tested for their suitability for studying the role of prostaglandins in peristalsis. Aspirin was suitable; at 10-200 mug/ml it had little effect on responses of longitudinal muscle strips of the guinea-pig ileum to acetylcholine (ACh), histamine, nicotine or prostaglandin E2. Indomethacin (1-4 mug/ml) reduced responses to nicotine and prostaglandin E2. The prostaglandin antagonists polyphloretin phosphate and SC-19220 reduced contractions of ileal longitudinal muscle caused by nerve excitation with either nicotine or transmural stimulation. 3 Aspirin (20-100 mug/ml) or indomethacin (1-4 mug/ml) applied serosally greatly inhibited all aspects of peristalsis in guinea-pig ileum and colon. Inhibition of peristalsis of the ileum by aspirin was antagonized by prostaglandin E2 and that by indomethacin was removed by prostaglandin F2alpha or ACh. Inhibition of colonic peristalsis by aspirin was antagonized by prostaglandin E2 but rarely by ACh, and that by indomethacin by prostaglandin E1 or E2. Mucosal application of aspirin had little effect on either ileum or colon but indomethacin caused some inhibition. 4 These results support the supposition that prostaglandins contribute to peristaltic activity.     

Modification by capsaicin and compound 48/80 of dye leakage induced by irritants in the rat.

Concentration-related dye leakage produced by intracutaneous injections of irritants was measured in rats by an Evans blue technique. 2 In rats pretreated with a total dose of 50 mg capasaicin over 4 days, the response to capsaicin, formalin, HCl, KCl, prostaglandin E1, bradykinin and bradykinin with prostglandin E1 (10(-6) M) were greatly reduced, the responses to histamine and 5-hydroxytryptamine were slightly reduced and those to adenosine 5'-triphosphate (ATP) and compound 48/80 were unaffected. 3 Pretreatment with intracutaneous injections of compound 48/80 (0.5 mug, 24 and 48 h previously) recuded the responses to ATP, compound 48/80, HCl, KCl, prostaglandin E1, and bradykinin but did not affect those to histamine, 5-hydroxytryptamine or bradykinin with prostaglandin E1 (10(-6) M). 4 Responses to capsaicin and formalin produced spotted blueing extending over a large area and were suppressed by compound 48/80 in the smaller pretreated area only. Capsaicin responses were reduced with larger doses of compound 48/80 (total dose 15 mug). 5 It is concluded that the production of neurogenic oedema involves both sensory nerves and mast cells.     

The effect of catecholamines on the in vivo and in vitro responses of the cat lung during anaphylaxis.

1. Anaphylaxis in the lung of cats actively sensitized to Ascaris antigen has been investigated in vivo and in vitro. 2. In vivo there was a 100% increase in airways resistance and a 50% decrease in dynamic lung compliance following intravenous challenge with Ascaris antigen. Prostaglandin F2alpha induced similar changes but with histamine only dynamic lung compliance was affected. (-)-Isoprenaline prevented these prostaglandin F2alpha- and histamine-induced changes and caused a delay of about 2 min in the onset of the mechanical changes following anaphylactic challenge. 3. In vitro the isolated lung strip contracted within seconds of challenge whereas there was a delay of 2 to 3 min in the onset of the tracheal anaphylactic response. (-)-Isoprenaline, (-)-adrenaline and (+/-)-noradrenaline reduced the magnitude of anaphylactic contractions of the isolated trachea but did not significantly affect those of the isolated lung strip. This indicated lack of inhibition of mediator release from the lung parenchyma. 4. Histamine was released from sensitized lung fragments following challenge with the Ascaris extract. This release constituted 6.3% of the total tissue histamine and was not inhibited by (-)-isoprenaline (1 micrometer). 5. (-)-Isoprenaline abolished 5-hydroxytryptamine (5-HT)-induced contractions of the isolated trachea but not those elicited in response to acetylcholine. The isolated lung strip responses to histamine, prostaglandin F2alpha and 5-HT were highly resistant to inhibition by (-)-isoprenaline.     

Atypical (relaxant) response to histamine in cat bronchus.

Histamine, 2-methylhistamine (a specific H1-receptor agonist), 4-methylhistamine (a specific H2-receptor agonist), isoprenaline, bradykinin, prostaglandin E1, E2, and F 2alpha induce relaxation of carbachol-contracted isolated cat bronchial strips and tracheal chains. Bovine SRS-A contracts bronchus but not trachea. Histamine-induced relaxation of cat bronchus is not blocked by mepyramine (a specific H1-receptor antagonist); metiamide or burimamide (specific H2-receptor antagonists); propranolol ( a beta-adrenoceptor blocker) and indomethacin (a PG-synthetase inhibitor) suggesting non-participation of H1,H2-histamine receptors, beta-adrenoceptors (catecholamine release) and prostaglandin release in histamine-induced broncho-relaxations in the cat. The existence of an atypical histamine response, resistant to both H1- and H2-receptor antagonists is thus established in cat bronchus.     

Mechanisms of histamine release by compound 48/80

1. Rat and guinea-pig lung tissues were incubated for 20 min at 37 degrees C in Krebs-Ringer phosphate buffer at pH 7.4, or in Tyrode-Tris buffer at pH 8.2, and the release of histamine produced by adding different concentrations of compound 48/80 to the incubation medium was determined.2. At pH 7.4, increasing concentrations of 48/80 increased the release of histamine from the rat lung, with a tendency towards a maximum. No release of histamine from guinea-pig lung was observed at this pH. At pH 8.2, histamine release occurred both from rat and guinea-pig lung, and was proportional to the logarithm of the concentration of compound 48/80.3. Histamine release from rat lung by 20 mug/ml. of 48/80 decreased when the pH was raised from 7.4 to 8.2; but the release caused by 1 mg/ml. of 48/80 increased both in rat and guinea-pig lung as the pH was raised.4. 2-4-Dinitrophenol (DNP) inhibited the release of histamine from rat lung by a concentration of 20 mug/ml. of 48/80; the inhibition was prevented by glucose. DNP did not affect histamine release from rat or guinea-pig lung by a concentration of 1 mg/ml. of 48/80 and enhanced the release when the pH was raised from 7.4 to 8.2.5. 1 mg/ml. of 48/80 did not inhibit the enhanced oxygen consumption produced by DNP in the isolated rat diaphragm.6. Iodoacetic acid (IAA) or a Ca/Mg-free medium inhibited the release of histamine by 20 mug/ml. of 48/80 from rat lung but not the release produced by 1 mg/ml. in either rat or guinea-pig lung.7. The degranulation of rat mesentery mast cells caused by 20 mug/ml. of compound 48/80 was inhibited by DNP. The degranulation evoked by 1 mg/ml. of 48/80 was also sensitive to this inhibitor; in this instance, however, the metachromatic staining reaction of the mesentery mast cells was greatly diminished.8. It is concluded that two processes of histamine release by compound 48/80 occur in rat lung. One, dependent on cell metabolism, involves, mast cell granule secretion. The other, independent of cell metabolism, seems to consist of a simple exchange reaction between histamine and compound 48/80, and this is the only one occurring in guinea-pig lung.     

Mediation of prostaglandin E2 in the biphasic response to ATP of the isolated tracheal muscle of guinea-pigs.

ATP, at a dose higher than 0-1 mug m1(-1), showed a biphasic action consisting of an initial increase followed by a gradual decrease of muscle tension in the isolated tracheal strip-chains of guinea-pigs. The pattern of this biphasic response to ATP varied with the level of basal tone of the preparation at the moment of application of ATP. A smiliar biphasic action was obtained by prostaglandin (PG) E2 among the various active substances studied including acetylcholine, histamine, catecholamines and various types of PG. Indomethacin (0-1 mug m1(-1) and aspirin (30 mug m1(-1)) completely abolished the ATP-induced inhibitory response observed in the presence of histamine (10 muM). Polyphloretin phosphate (100 mug m1(-1)) also significantly depressed the inhibitory response to ATP or PGE2. It is concluded that the response to ATP of the preparation is mediated by PGE2 released via the stimulation of its biosynthesis.     

Interaction between prostaglandins and gonadotrophins in the rabbit ovary

1. It has been suggested that prostaglandins function as feedback modulators of hormonal actions which are mediated by adenosine 3',5'-monophosphate (cyclic AMP). This hypothesis has been tested on the rabbit ovary, whose steroidogenic response to luteinizing hormone (LH) is mediated by the cyclic nucleotide.2. Prostaglandin E(1) (1-100 mug/ml) reduced the production of progesterone by rabbit ovaries incubated in the presence of a submaximal concentration of LH, but had no effect on the formation of this steroid when exogenous cyclic AMP was used as the stimulating agent. The prostaglandin was without effect on the formation of 20alpha-hydroxypregn-4-en-3-one in the presence of either LH or cyclic AMP.3. Prostaglandin E(2) (1 mug/ml) was without effect on ovarian steroidogenesis in the presence of LH.4. There was no evidence that exogenous prostaglandin E(1) was inactivated during incubation with rabbit ovaries in the presence of LH.5. Prostaglandin E-like compounds were detected in homogenates of incubated rabbit ovaries. However, concentrations of LH sufficient to stimulate steroidogenesis did not stimulate the synthesis of these compounds by the ovary in vitro, nor their release from the ovary in vivo.6. It is concluded that the prostaglandin-like compounds detected in the ovary are unlikely to play a role in the regulation of steroidogenesis. The results of this investigation do not support the hypothesis that prostaglandins function as general modulators of hormonal actions which are mediated by cyclic AMP.     

Interaction between prostaglandins E and F given intradermally in the rat

1. Increases in permeability observed after intradermal injection of prostaglandins PGE(1) or PGE(2) (0.1 mug) into rats were greatly reduced when they were given in admixture with PGF(2alpha). This effect was not seen with PGF(1alpha) at doses of 0.5-1 mug.2. Effects of the histamine releasing agent compound 48/80 (25 ng) were inhibited by PGF(2alpha) (0.5 mug) but not by PGF(1alpha) (0.5 mug).3. Responses to histamine (1 mug), 5-hydroxytryptamine (0.1 mug) and bradykinin (1 mug), which have a direct action on the microvasculature, were not significantly altered by PGF(2alpha) (0.5 mug).4. It is concluded that PGF(2alpha) probably acts by interfering with the release of mast cell histamine by PGE(1), PGE(2) and compound 48/80.     

Release of smooth muscle-contracting substances from isolated perfused lungs.

Infusion of tryptamine (1-4 mug/ml) through the pulmonary circulation of rat isolated lung perfused with Krebs solution caused release of a mixture of spasmogens contracting isolated smooth muscle preparations. One component of this mixture had biological activity comparable to E-type prostaglandins. Other components included a slow reacting substance comparable to SRS-A and a rabbit aorta-contracting substance comparable to RCS. Infusions of 5-hydroxytryptamine, acetylcholine and histamine (0.5-2 mug/ml) also caused release. Release induced by the tryptamines but not that by acetylcholine and histamine was prevented by methysergide whereas acetylcholine-induced release was prevented by hyoscine which did not affect tryptamine-induced release. The tryptamines and histamine released spasmogens from dog isolated lungs but only histamine was effective in guinea-pig lungs. We conclude that amine-induced release from isolated lungs is a fairly general phenomenon and that it may represent an endocrine function of lung.     

The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea.

1 A new in vitro preparation, the isolated lung strip of the cat, is described for investigating the direct effect of drugs on the smooth muscle of the peripheral airways of the lung. The preparation comprises a thin strip of lung parenchyma which can be mounted in a conventional organ bath for isometric tension recording. Its pharmacological responses have been characterized and compared with the isolated tracheal preparation of the cat. 2 The lung strip exhibited an intrinsic tone which was relaxed by catecholamines, aminophylline and flufenamate. It was contracted strongly by histamine, prostaglandin F2alpha, acetylcholine, compound 48/80, potassium depolarizing solution and alternating current field stimulation. In contrast, the cat trachea was unresponsive to histamine and prostaglandin F2alpha and did not exhibit an intrinsic tone. 3 (-)-Isoprenaline and (-)-adrenaline were much more potent in relaxing the lung strip than the trachea. The potency order of relaxation responses to isoprenaline, adrenaline and (+/-)-noradrenaline in the lung strip was isoprenaline greater than adrenaline greater than noradrenaline but in the trachea was isoprenaline greater than noradrenaline greater than or equal to adrenaline. 4 beta2-Adrenoceptor selective agonists salbutamol and terbutaline were more potent in the lung strip than the trachea, suggesting beta2-adrenoceptors predominated in the lung strip. Propranolol was equipotent in inhibiting isoprenaline relexations of the lung strip and trachea, whereas practolol was much less effective in inhibiting lung strip than trachea, further supporting a predominance of beta2-adrenoceptors in lung strip and beta1-adrenoceptors in trachea. 5 Strong Schultz-Dale type contractions were elicited in both lung strips and trachea by Ascaris lumbricoides antigen in actively sensitized cats. The initial phase of the contractile response of the lung strip following challenge was shown to be due to histamine release and was absent in the trachea. The delayed phase of the contraction which took several minutes to develop in both the mepyramine-treated lung strip and trachea was not due to prostaglandins E1, F2alpha or bradykinin, the probable mediator being slow reacting substance of anaphylaxis (SRS-A). 6 It is concluded that the isolated lung strip of the cat is useful as an in vitro model for investigating the effect of drugs on the smooth muscle of the peripheral airways of the lungs.     

Stimulation of the antigen-induced contraction of guinea-pig trachea and immunological release of histamine and SRS-A from sensitized guinea-pig lung by (2-isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin.

1 (2-Isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin reduced basal tension and enhanced the antigen- and histamine-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. The stimulating effect of L8027 required the presence of the drug, while that of indomethacin persisted after its removal from the organ bath. 2 L8027 and indomethacin stimulated the immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) and inhibited the de novo synthesis and release of malondialdehyde from actively sensitized guinea-pig lung fragments. 3 L8027 was 2,800 times more potent than indomethacin in both in vitro models of anaphylaxis. 4 A selective antagonist of SRS-A (FPL 55712) inhibited contractions produced by antigen, but had no effect on contractions produced by histamine. 5 Prostaglandins E and F2 alpha were continuously released into the organ bath fluid by the resting trachea. Contractions induced by antigen or histamine increased the rate of prostaglandin efflux. 6 L8027 had no effect on the efflux of prostaglandins E and F2 alpha at rest and during contraction. Indomethacin inhibited prostaglandin efflux at rest and during contraction while present in the organ bath. Prostaglandin efflux was restored to 80% of control after removal of indomethacin. 7 The results suggest that prostaglandins E and F2 alpha have no role in the stimulation by L8027 and indomethacin of the contractile responses of guinea-pig trachea. The possible mechanism for the effects of these drugs is discussed.     

Regional differences in the mechanical properties of rabbit airway smooth muscle.

1. In studies of rabbit airway smooth muscle, differences in mechanical responses to acetylcholine, histamine and high K+ in intact muscles, and in Ca2+ sensitivity in skinned muscles, have been examined in tissue taken from 5 different regions of the airway. Interactions between prostaglandin F2 alpha and epithio-thromboxane A2 and the above spasmogenic agencies were also studied. 2. Mechanical responses to histamine (10 microM) and to 128 mM K+ were smallest in trachea and were largest in 3rd and 4th order bronchi. In all regions, spasm evoked by 10 microM acetylcholine was greater than that evoked by 10 microM histamine or 128 mM K+. 3. In the third and fourth branches of the rabbit right middle bronchus, contractions evoked by 10 microM acetylcholine, 10 microM histamine and 128 mM K+ showed similar amplitudes of phasic response. In Ca2+-free solution containing 2 mM EGTA, the phasic components of the acetylcholine- or histamine-induced contraction remained unchanged in comparison with that observed in Krebs solution, but the phasic and tonic components of the K+-induced contraction and the tonic changes induced by acetylcholine and histamine were abolished. 4. Two subtypes of the histamine receptor, excitatory H1- and inhibitory H2- receptors were detected on the bronchial smooth muscle. The H1-induced contraction was mediated by release of stored Ca2+ together with activation of Ca2+ influx relatively insensitive to Ca2+ antagonists. 5. The -log(EC50) values for acetylcholine and histamine (in the presence of cimetidine and atropine) were 6.11 +/- 0.11 and 5.33 +/- 0.08, respectively, in the third branch of right middle bronchus. These values were similar to those observed for trachea.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of prostaglandin E1 on acid secretion, mucosal histamine content and histidine decarboxylase activity in rat stomach

1. Prostaglandin E(1) inhibits basal and pentagastrin-stimulated gastric acid secretion. The mechanism of this action is not clear. One possible explanation might be that prostaglandin E(1) interferes with the local release or synthesis of histamine which has been proposed as the mediator of the effects of gastrin on the parietal cell.2. A single injection of prostaglandin E(1) did not affect mucosal histamine content or histidine decarboxylase activity in the rat stomach. Pentagastrin lowered the histamine content and activated the histidine decarboxylase to the same extent in prostaglandin E(1)-pretreated and in control rats. We conclude therefore that the inhibitory effect of prostaglandin E(1) on basal and pentagastrin-stimulated acid secretion is not caused by inhibition of histamine release or histamine synthesis.3. Repeated injections of prostaglandin E(1) resulted in a significant elevation of the gastric histidine decarboxylase activity in normal but not in antrectomized rats. Conceivably, this increase in enzyme activity is secondary to prostaglandin E(1)-induced inhibition of acid secretion, which will stimulate release of gastrin due to the rise in intragastric pH.     

Mechanism of histamine-induced antidiuretic response

1. In dogs anaesthetized with alpha-chloralose, intracerebroventricular (i.c.v.) injection of histamine induced antidiuresis and increase in jugular vein blood antidiuretic hormone (ADH) level but no change in urinary electrolytes. The mechanism of the histamine-induced antidiuretic response was analysed by the use of pharmacological agents.2. Histamine (i.c.v.) in 1-20 mug doses produced a variable effect on urine outflow as well as on the blood ADH concentration; however, higher doses (25-500 mug) of histamine elicited a dose-dependent antidiuretic response with concomitant rise in blood ADH titre.3. Repeated administration of high doses of i.c.v. histamine (400 mug) elicited a diminishing antidiuretic response which was not observable after the fourth dose, thus exhibiting tachyphylaxis. The antidiuretic response to histamine could be restored by central administration of noradrenaline (500 mug).4. Central pretreatment with mepyramine (5 mg) prevented the histamine-induced antidiuresis. Atropine (2 mg i.c.v.) was ineffective in blocking the antidiuretic effect of histamine. A diuretic response to histamine (400 mug i.c.v.) was obtained in phenoxybenzamine (i.c.v.) pretreated animals; this response could be blocked by i.c.v. injection of propranolol. Tetrabenazine pretreatment prevented the antidiuretic response to histamine.5. The results of the study lead us to conclude that histamine releases central catecholamines which activate the central adrenergic mechanism for the release of antidiuretic hormone.     

Effect of synthetic bradykinin on contractile tension of human saphenous vein strips

The ability of synthetic bradykinin to contract isolated, helically-cut human saphenous vein strips was studied in vitro. Bradykinin (0.05-2.0,mug/ml) consistently failed to contract human vein strips. Similarly prepared rabbit aortic strips also failed to contract when exposed to bradykinin in the concentration range studied. Bradykinin-insensitive vein and aortic strips responded with substantial increases in contractile tension when exposed to prostaglandin E(2), noradrenaline, histamine and KC1. However, bradykinin (0.1,mug/ml) was, capable of relaxing human vein strips, which had contracted in response to prostaglandin E(2).