Responses Of Rabbit Aortic Strips Research Articles

Inhibition of rabbit aortic angiotensin II (AII) receptor by CV-11974, a new nonpeptide AII antagonist

The angiotensin II (AII) antagonistic action of CV-11974 (2-ethoxy-1-[[2'-(1 H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid) was investigated in an AII-receptor binding assay using rabbit aortic membranes and an AII-induced contraction assay using rabbit aortic strips. A single class of [ 125I]AII-(Sar 1,Ile 8) binding sites was found in the membranes with a dissociation constant ( K d ) of 0.15 nM and a receptor concentration ( B max) of 86.9 fmol/mg protein. CV-11974 markedly reduced K d without affecting B max. The specific binding of [ 125I]AII-(Sar 1,Ile 8) in this preparation was inhibited competely by CV-11974 [the inhibition constant ( K i ) = 0.64 nM], DuP 753 [an angiotensin II type I (at 1) receptor-selective antagonist] ( K i = 51 nM) and EXP3174 (an active metabolite of DuP 753) ( K i = 6.8 nM), but was not affected by PD123177 (an AT 2 receptor-selective antagonist). These results suggest that the single binding site in rabbit aortic membranes is an AT 1 receptor subtype. The affinity of CV-11974 to these AT 1 receptors was approximately 80 and 10 times higher than that of DuP 753 and EXP3174, respectively. CV-11974 showed no appreciable affinity for the AT 2 receptors found in bovine cerebellum. In the in vitro functional study, CV-11974 markedly reduced the AII-induced maximal contractile response of rabbit aortic strips (pD' 2 = 9.97). In contrast. Compound 7-H, which lacks the carboxyl group at the benzimidazole ring of CV-11974, inhibited the contraction in a competitive manner. The inhibition by CV-11974 was long lasting. These results suggest that CV-11974 is a potent and long-acting AT 1 receptor-selective, competitive antagonist. The carboxyl group at the benzimidazole ring plays an important role in the interaction between CV-11974 and the AT 1 receptor.

Mechanisms of the endothelium-dependent relaxation induced by NG-hydroxy-L-arginine.

There are three mechanisms by which NG-hydroxy-L-arginine (L-HOArg) induces endothelium-dependent relaxations. L-HOArg is a substrate for the constitutive nitric oxide (NO) synthase present in endothelial cells (ECs). It reacts with NO released from EC to form a potent and more stable vasodilator. Moreover, it induces a relatively stable, EC-dependent relaxation that is not blocked by the inhibitors of NO synthesis. Subsequently, we have investigated the effects of hydroxyguanidine (HOG) on the biological activity of endothelium-derived relaxing factor (EDRF). HOG potentiated the relaxant responses of rabbit aortic strips to EDRF released from EC by adenosine diphosphate (ADP) or bradykinin as well as those induced by authentic NO. Importantly, it was not a substrate for NO synthesis and it did not affect the generation of prostacyclin by ECs. Thus, the effects of HOG were due to the chemical reaction of HOG with NO released from ECs and the formation of a more stable vasodilator. Moreover, HOG augmented not only agonist-triggered, but also flow-induced, EC-dependent relaxation and both effects of HOG were abolished by NG-nitro-L-arginine methyl ester (L-NO2-Arg). In contrast, the EC-dependent relaxation induced by L-HOArg was not inhibited by L-NO2Arg. Moreover, it was not affected by the removal of extracellular Ca2+, but was blocked by oxyhemoglobin and potentiated by superoxide dismutase. These results demonstrate the involvement of the hydroxyguanidino moiety of L-HOArg in its reaction with NO. Moreover, they strongly support the notion that nitrix oxide mediates both the agonist-triggered and flow-induced endothelium-dependent relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Facilitating effect of amphetamine on the response of rabbit aortic strips to adrenaline, dopamine and serotonin

Amphetamine increased the response of rabbit aortic strips to adrenaline, dopamine and serotonin at consistently lower doses than those exerting a direct contracting effect. The amphetamine-facilitated contraction had the same shape as that produced by biogenic amines alone, whereas the contraction produced by amphetamine alone was more delayed and flatter. Serotonin and dopamine facilitated each other, but less markedly and with a narrower interval between facilitating and contracting doses than amphetamine. Pargyline exerted no facilitating effect on biogenic amines. Phentolamine and prazosin inhibited the direct response to adrenaline, dopamine and amphetamine, and the amphetamine-facilitated response to adrenaline and dopamine; they were inactive against serotonin alone and combined with a facilitating dose of amphetamine or dopamine. Cyproheptadine inhibited the direct response to serotonin and amphetamine, and the amphetamine-facilitated response to serotonin; it was inactive against dopamine and adrenaline both alone and combined with a facilitating dose of amphetamine or serotonin.

Mass analysis of 1,2-diacylglycerol in cultured rabbit vascular smooth muscle cells. Comparison of stimulation by angiotensin II and endothelin.

We compared the effects of angiotensin II and endothelin on mass levels of 1,2-diacylglycerol, and endogenous activator of protein kinase C, in cultured rabbit vascular smooth muscle cells with the effects of these vasoconstrictors on contractile responses of rabbit aortic strips. At a high concentration (1 microM), both angiotensin II and endothelin induced a biphasic formation of 1,2-diacylglycerol with an early transient phase and a late sustained phase. At this high concentration, angiotensin II caused a transient contraction followed by a gradual relaxation, whereas endothelin caused a slowly developing and sustained contraction. At a low concentration (EC50 for the early phase of 1,2-diacylglycerol formation), angiotensin II also induced a biphasic formation of 1,2-diacylglycerol and caused a transient contraction, but endothelin induced a monophasic formation of 1,2-diacyglycerol with only an early peak. Despite a rapid decrease of 1,2-diacylglycerol, endothelin at this low concentration still caused a sustained contraction. At both the high and low concentrations, the 1,2-diacylglycerol level was sustained higher for angiotensin II, whereas the tension during the late tonic phase of contraction was greater for endothelin. These results suggest that the unique persistent nature of endothelin-induced contraction is not attributed simply to the stimulatory effect of this peptide on the 1,2-diacylglycerol/protein kinase C pathway.

Effects of hypoxia on contractile responses of rabbit aortic strips to transmural electrical stimulation.

To clarify the effects of hypoxia on adrenergic transmission, we examined the contractile responses of isolated rabbit aortic strips to electrical stimulation, the concentration-response relationships for noradrenaline and KCl, and the electrical stimulation-evoked overflows of total [3H] and [3H]noradrenaline from strips preloaded with [3H]noradrenaline in media equilibrated with gas mixtures containing various concentrations of O2. Contractile responses to electrical stimulation were completely inhibited by tetrodotoxin and alpha-adrenoceptor antagonists such as phentolamine and phenoxybenzamine, but were not affected by indomethacin. When the concentration of O2 in the gas mixture was decreased from 95% to 20%, the contractile responses to electrical stimulation remained unchanged, but as the concentration of O2 was further decreased, the responses were inhibited concentration-dependently. At 0% O2, the response was inhibited by about 80% when compared with control values obtained at 95% O2, and the electrical stimulation-evoked overflows of total [3H] and [3H]noradrenaline into the superfusates were decreased by about 55%. At 0% O2, the concentration-response curve for exogenous noradrenaline was shifted to the right about 50-fold and the maximum response was decreased by 25%. The maximum contractile responses of aortic strips from animals pretreated with reserpine or 6-hydroxydopamine to high KCl were decreased slightly (about 15%). These results suggest that inhibition of adrenergic transmission under hypoxic conditions is mainly the result of a decrease in the stimulus-evoked release of noradrenaline and of a decrease in the affinity of alpha-adrenoceptor for noradrenaline and/or inhibition of signal transduction mechanisms, although hypoxia also causes a slight decrease in the contractility of vascular smooth muscle.

C-6-Sulfidopeptide leukotrienes are unlikely to be involved in the endothelium dependent relaxation of rabbit aorta by acetylcholine

Acetylcholine (ACh) induced dilation of precontracted strips of rabbit aorta by a mechanism dependent on an intact endothelium, probably by releasing an unknown endothelial relaxing factor (ERF). The relaxation was completely inhibited by the lipoxygenase inhibitor nor-dihydroguaiaretic acid (10 −5 M) but not by the cyclo-oxygenase inhibitor indomethacin (10 −5 M). The aortic strips were found to release small amounts of a material with a leukotriene-like activity. Its action on the guinea pig ileum was antagonized by FPL 55712 (10 −6 M). However, FPL 55712 (10 −6 - 10 −4 M) did not alter the response of rabbit aortic strips to ACh. Also when decreasing intracellular concentrations of glutathion (GSH) by incubating the strips with diethylmaleat or 2-cyclohexen-1-one (both 10 −3 M) the vasodilator response could still be elicited. Leukotriene (LT) C 4 and LTD 4 (10 −9 - 10 −10 M) were found to be ineffective on oartic strips under basal or induced tension. The same held true for LTE 4 ( 10 −9 - 10 −7 M). At 10 −6 M, however, LTE 4 induced slight relaxations of the vascular tissues. For reasons discussed this is likely to be a pharmacological action independent of the effects of endogenous ERF (e.g. inhibition of the formation of the LTE 4 precursor LTD 4 by high extracellular GSH concentrations did not reverse the ACh-induced vasodilation). It is concluded from these data, that C-6-sulfidopeptide leukotrienes, although probably produced by vascular tissue, are unlikely to be involved in the ACh-induced relaxation of rabbit aorta.

Modifications by lidocaine and its N-dealkylated metabolites of the response of the isolated rabbit aorta to transmural electrical stimulation.

Contractile responses of rabbit aortic strips to transmural stimulation and to exogenously applied norepinephrine (NE), potassium chloride (KCl), and histamine were studied in the presence of lidocaine or its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). Lidocaine, 10(-4) and 5 x 10(-4) M, attenuated the contractile response to transmural stimulation, whereas MEGX, 2 x 10(-5) and 10(-4) M, potentiated, but 10(-4) M, potentiated the response to transmural stimulation. The suppression induced by lidocaine and MEGX was not reversed by excess calcium, 2.2 and 4.4 mM, but was partially reversed by cocaine, 3 x 10(-6) M. Lidoncaine, 5 x 10(-4) M, and MEGX, 2 x 10(-3) M, shifted the dose-response curve of NE to the right, whereas GX, 5 x 10(-4) M, shifted the curve to the left. The maximum tension developed by K+ was attenuated by lidocaine, 5 x 10(-4) M, MEGX, 5 x 10(-4) and 2 x 10(-3) M, and GX, 2 x 10(-3) M. It may be concluded that lidocaine attenuates the response to stimulation of sympathetic nerves innervating the arterial wall by interfering with the release of NE. In contrast, the metabolites, MEGX and GX, potentiate the response, possibly by increasing the release of NE. MEGX in high concentrations appears to have the same mechanism of inhibitory action as does lidocaine.

Potentiation of the contractile response to acetylcholine in aortic strips by low concentrations of vascular contractile agonists.

1 The potentiating effect of a low concentration of various vascular contractile agonists on the response of rabbit aortic strips to acetylcholine was examined. 2 A marked parallel displacement to the left (potentiation; not additive effect) of the dose-response curve for acetylcholine was observed when 5-hydroxytryptamine (5-HT), noradrenaline, histamine, angiotensin II or KCl were added at a concentration that caused only slight contraction (0.2 to 0.3 g) in the strips. This leftward displacement (potentiation) of the dose-response curve by these agonists was reversed to the control response curve by the respective blocking agents for each agonist, although the blocking agents themselves did not shift the acetylcholine dose-response curve to the right. Atropine produced a rightward displacement of the dose-response curve for acetylcholine. 3 The addition of an extremely low concentration of 5-HT or KCl which did not cause contraction, also produced a potentiation. 4 The order of potency of the agonists in potentiating the acetylcholine-induced contraction was KCl > 5-HT greater than or equal to histamine greater than or equal to angiotensin II > noradrenaline. 5 The contractile response of aortic strips to carbamylcholine was also potentiated by these agonists. 6 The results suggest that the potentiation by these agonists was not mediated through muscarinic receptors but through the respective receptors for each agonist.

Action of histamine on phasic and tonic components of vascular smooth muscle contraction.

The isometric contractile response of rabbit aortic strips in response to histamine was studied. Biphasic dose-dependent contractions reflecting release of internal Ca2+ (phasic component) and simultaneous mobilization of external Ca2+ stores (tonic component) were produced.

Angiotensin II Responses of Rabbit Aortic Strips Compared with Fast and Slow Epinephrine Responses

SummaryEpinephrine causes a biphasic contraction of rabbit aorta, consisting of (i) a fast component, F, ascribed to release of intracellular calcium, and (ii) a slow component, S, ascribed to calcium movement into the muscle cell. Angiotensin produces a single-phase contraction of uncertain calcium source. Insight into the latter might be gained if angiotensin contractions consistently resembled the F or S epinephrine response. Contractions of rabbit aorta strips produced by both drugs were therefore compared during five interventions which had dissociated effects on F or S epinephrine responses. These interventions consistently altered the angiotensin responses in the same way as they affected epinephrine F responses, and differently from their effects on epinephrine S responses. These results are compatible with the view that the likely major source of activator calcium for angi-otensin-induced contractions of rabbit aorta is intracellular, although a small extracellular calcium contribution could not ...

Factors determining the rate of relaxation of rabbit aortic strips after an exposure to noradrenaline.

1. When noradrenaline distributes exclusively into the: extraneuronal o-methylation of about one third of the extracellular space (i.e., when both, neuronal and extraneuronal uptake mechanisms are blocked by the presence of cocaine and corticosterone), the response of rabbit aortic strips to noradrenaline is concentration-dependent and relaxation curves (obtained during wash out and starting from different heights) are parallel. Under these conditions the "time required for relaxation to 50 or 20% of the initial contraction" (t50 and t20, respectively) is positively correlated with the initial height of contraction. 2. Measurements of the rate of relaxation that are independent of the height of the initial contraction are obtained either by appropriate correction of the t50 (or t20) or by determination of the "average rate of relaxation down to the 25% level of maximum contraction". 3. Relaxation experiments should a) be carried out with initial contractions of less than 75% of maximum and b) use a measure of the rate of relaxation that is independent of the initial height of contraction. 4. When the experimental conditions favour the extraneuronal accumulation of noradrenaline, corticosterone affects the relaxation of the strips in a way which is consistent with the view that efflux of unchanged amine from extraneuronal stores influences the rate of relaxation. 5. When extraneuonal uptake is operative and accumulation of noradrenaline is poor (i.e., when extraneuronal catechol-O-methyl transferase is intact), corticosterone affects relaxation in a way which is consistent with the view that normally the extraneuronal system serves as a site of loss. Under these conditions corticosterone prevented, during the first 5 min of wash out, the extracellularly distributed amine. 6. It is concluded that the experimental conditions of relaxation experiments determine whether the noradrenaline stores serve as a source of efflux of unchanged amine or as a site of loss.

Influence of Magnesium on Calcium- and Potassium-Related Responses in Vascular Smooth Muscle

The influence of Mg on Ca- and K-related responses of rabbit aortic strips was studied. Aortic strips bathed in either a K-free or 60.0 mM K solution were less sensitive to Ca in the presence of 1.2 mm Mg. Ca induced greater maximum tension in the aortic strips in the presence of Mg when bathed in 60.0 mM K. Addition of K to a K-free medium induced a slight relaxation at low concentrations (is less than 1.0 mm) which was Ca dependent. The relaxation was less in the presence of Mg. Wiolution were less sensitive to Ca in the presence of 1.2 mm Mg. Ca induced greater maximum tension in the aortic strips in the presence of Mg when bathed in 60.0 mm K. Addition of K to a K-free medium induced a slight relaxation at low concentrations (is less thth Mg in the medium throughout the experiment (90 min), the threshold concentration of K, including a contractile response, was increased as was the maximum tension. Acute addition of Mg decreased the maximum response to K. When K was lowered from 5.4 to 0.0 mm a contractile response, absent in the presence of Mg, occurred. When the K was increased, the tension returned to baseline. At 25-30 mm K, the tension again increased, reaching a maximum at 40-50 mm K. Ca uptake was stimulated at all K concentrations producing a contraction. Mg depressed this increase in uptake. 45Ca efflux was more rapid into a 50.0 mm than into 0.0 mm K solution. Mg delayed Ca efflux. It is concluded from these data that Mg has two components in its effect on the Ca associated with K responses. One is a competition with Ca at extracellular sites probably at the membrane, and the other is intracellular, probably a competition with Ca at sequestration sites.

Role of extraneuronal mechanisms in the termination of contractile responses to amines in vascular tissue.

1 The role of the uptake and release of agonist from extraneuronal sites in the termination of responses of rabbit aortic strips to amines was studied. 2 Strips were contracted with adrenaline or noradrenaline and after response plateau was reached, the muscle chambers were washed free of agonist and the relaxation in Krebs solution recorded. After inhibition of catechol-O-methyl-transferase, monoamine oxidase and neuronal uptake the relaxation rate was greatly prolonged. Evidence is provided that this very slow relaxation resulted from the accumulation of intact amine at extraneuronal sites during exposure to the agonist and its subsequent release past receptors due to a reversal of the concentration gradient after washout. 3 Pretreatment with the haloalkylamine, GD-131 (N-cyclohexylmethyl-N-ethyl-beta-chloroethylamine), an inhibitor of extraneuronal uptake, returned the slow relaxation rate after enzyme inhibition towards that of control strips. By blocking the extraneuronal transport of amines their accumulation at intracellular loci after enzyme inhibition was prevented. 4 The effects of GD-131 and 17beta-oestradiol on the relaxation rate of untreated strips contracted by adrenaline and noradrenaline confirmed that extraneuronal uptake to sites of enzymatic activity is the major mechanism terminating their action. 5 Inactivation of extraneuronal transport sites by GD-131 was prevented by protecting them with 17beta-oestradiol or normetanephrine during exposure to the haloalkylamine, pointing to a common site of action of these agents on a specific carrier system for amines. 6 Evidence is presented that the relaxation from contractions induced by histamine and 5-hydroxytryptamine also involves extraneuronal accumulation and release, probably by an uptake process which is identical to the one for catecholamines.

A new approach to the measurement and classification of forms of supersensitivity of autonomic effector responses.

1 It is proposed that sensitizations of autonomic effectors to agonists by drugs or procedures be considered in two main categories: those involving changes in the effective concentration of agonist at receptors (type I) and those involving changes in the responding tissue beyond the initial combination of agonist and receptors (type II). Type I sensitizations are appropriately described by determining the dose-ratio (horizontal shift of the dose-response curve) and type II sensitizations by assessing the change in the magnitude of the response.2 The inadequacy of the dose-ratio in assessing sensitizations related to an altered physiology of the responding tissue is illustrated by means of hypothetical examples with particular reference to the slopes of dose-response curves and altered maximal responses.3 An evaluation of the enhancement of responses of rabbit aortic strips to agonists by reserpine indicates that it is a type II sensitization. The shifts of dose-response curves to noradrenaline, isoprenaline, normetanephrine and 5-hydroxytryptamine after reserpine-treatment, were described both by the dose-ratio and by the increment in the magnitude of the response at various contraction amplitudes. The dose-ratio varied unpredictably for each agonist depending on the response level selected for comparison and also varied between agonists. However, the mm increment in response magnitude after reserpine approximated a constant value. Responses to potassium which by horizontal procedures were assessed among the least increased, were found to be enhanced the most when considered as a type II sensitization.4 It is concluded that both type I and type II procedures should be applied when dealing with an unidentified sensitization and that the data be critically assessed. The appropriate use of these procedures can aid in identifying and clarifying sensitizations, as well as in elucidating the sequence of steps between receptor activation and response in an effector.

THE EFFECT OF COCAINE ON CATECHOL-O-METHYL-TRANSFERASE AND ON THE RESPONSE TO NOREPINEPHRINE OF RABBIT AORTIC STRIPS

The ability of cocaine to produce supersensitivity of catecholamines has been demonstrated in a variety of adrenergically innervated systems. The mechanism of this supersensitivity is generally thought to involve impairment of amine uptake by the adrenergic nerves resulting in a shift of the amine from the nerve endings to the receptors and a consequent increase in the response of the effector organ or supersensitivity. Contrary to this, several investigators have recently suggested that the sensitizing action of cocaine on the blood vessels cannot be attributed entirely to its ability to inhibit the uptake of the amine (1–5). Cold storage preparations have shown such supersensitivity without the inhibition of amine uptake (3). Kalsner and Nickerson (5) point out that enzymatic pathways are as important in the inactivation of physiological concentrations of amines as the amine uptake mechanisms, the site of the sensitizing action probably being post synaptic. Previous data indicated that the catechol-O-methyltransferase (COMT) inhibitor, pyrogallol, but not the monoamine oxidase (MAO) inhibitors (tranylcypromine and iproniazid), potentiated the response of rabbit aortic strips to norepinephrine (7, 8). However, there appears to be little known for an inhibitory action of cocaine on the extracellular norepinephrine-metabolizing enzyme, catechol-O-methyltransferase (9). The present study was therefore undertaken to investigate the relationship between the effect of cocaine on the COMT activity and the potentiation of norepinephrine-induced contraction.

The effect of cocaine on catechol-O-methyl-transferase and on the response to norepinephrine of rabbit aortic strips.

The ability of cocaine to produce supersensitivity of catecholamines has been demonstrated in a variety of adrenergically innervated systems. The mechanism of this supersensitivity is generally thought to involve impairment of amine uptake by the adrenergic nerves resulting in a shift of the amine from the nerve endings to the receptors and a consequent increase in the response of the effector organ or supersensitivity. Contrary to this, several investigators have recently suggested that the sensitizing action of cocaine on the blood vessels cannot be attributed entirely to its ability to inhibit the uptake of the amine (1–5). Cold storage preparations have shown such supersensitivity without the inhibition of amine uptake (3). Kalsner and Nickerson (5) point out that enzymatic pathways are as important in the inactivation of physiological concentrations of amines as the amine uptake mechanisms, the site of the sensitizing action probably being post synaptic. Previous data indicated that the catechol-O-methyltransferase (COMT) inhibitor, pyrogallol, but not the monoamine oxidase (MAO) inhibitors (tranylcypromine and iproniazid), potentiated the response of rabbit aortic strips to norepinephrine (7, 8). However, there appears to be little known for an inhibitory action of cocaine on the extracellular norepinephrine-metabolizing enzyme, catechol-O-methyltransferase (9). The present study was therefore undertaken to investigate the relationship between the effect of cocaine on the COMT activity and the potentiation of norepinephrine-induced contraction.

Mechanism of hydrocortisone potentiation of responses to epinephrine and norepinephrine in rabbit aorta.

Hydrocortisone potentiated responses of rabbit aortic strips to catecholamines (epinephrine, norepinephrine, nordefrin, isoproterenol) but not to amines lacking the catechol nucleus (phenylephrine, synephrine, methoxamine). Contractions in response to epinephrine were increased much more than those to norepinephrine. Neither the presence of cocaine nor pretreatment of the rabbits with reserpine impaired the potentiating action of hydrocortisone. Experiments with the oil immersion technique (to prevent loss of amine by diffusion from the tissue) demonstrated that hydrocortisone reduced the rate at which aortic strips inactivated epinephrine, apparently by inhibiting catechol-O-methyl transferase (COMT). Known inhibitors of COMT (U-0521, tropolone, pyrogallol) potentiated responses of aortic strips to epinephrine much more than to norepinephrine and also enhanced responses to isoproterenol and nordefrin to the same extent as did hydrocortisone. Known inhibitors of COMT consistently abolished the enhancing effects of hydrocortisone without materially interfering with potentiation produced by cocaine which is mediated through an independent mechanism unrelated to amine inactivation. Hydrocortisone also abolished the enhancing effects of known COMT inhibitors. It is concluded that hydrocortisone enhances the responses of vascular smooth muscle to epinephrine and norepinephrine by inhibiting a major enzymatic pathway for the inactivation of these amines.

THE POTENTIATION OF THE RESPONSES TO NORADRENALINE AND ISOPRENALINE OF THE GUINEA‐PIG ISOLATED TRACHEAL CHAIN PREPARATION BY DESIPRAMINE, COCAINE, PHENTOLAMINE, PHENOXYBENZAMINE, GUANETHIDINE, METANEPHRINE AND COOLING

THE POTENTIATION OF THE RESPONSES TO NORADRENALINE AND ISOPRENALINE OF THE GUINEA‐PIG ISOLATED TRACHEAL CHAIN PREPARATION BY DESIPRAMINE, COCAINE, PHENTOLAMINE, PHENOXYBENZAMINE, GUANETHIDINE, METANEPHRINE AND COOLING

RESPONSE OF RABBIT AORTIC STRIPS UNDER PULSED-TENSION TO CATECHOLAMINES.

SummaryA technique for studying the pharmacology of vascular smooth muscle has been described. This technique utilizes pulsed tension rather than the static tension customarily employed and has permitted the following observations: Contraction responses to the catecholamines have shown accelerated onset and recovery with increased uniformity of response. A differential sensitivity to norepinephrine has been shown to exist in segments taken from different parts of the same aorta. A progressive reduction in sensitivity to norepinephrine was observed from the arch to the origin of the superior mesenteric artery.

Effects of general anesthetics on contractile responses of rabbit aortic strips.

Effects of general anesthetics on contractile responses of rabbit aortic strips.