Rabbit Aortic Strips Research Articles

In Vitro Pharmacology of DuP 753

DuP 753, 2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H-tetrazol-5-yl) biphenyl-4-yl)methyl]imidazole, potassium salt, was characterized in vitro with respect to its affinity and specificity for functional antagonism of angiotensin II (AII) receptors. In rat adrenal cortical microsomes and cultured aortic smooth muscle cells DuP 753 inhibited the specific binding of [125I]AII in a concentration-dependent manner yielding IC50 values of 1.7 and 2.0 x 10(-8) mol/L, respectively. In contrast, DuP 753 had no appreciable affinity for other receptor systems as well as for Ca2+ channels. Functional antagonism was demonstrated by its blockade of AII-induced 45Ca2+ efflux in rat smooth muscle cells. The AII-induced contraction of rabbit aortic strips was competitively antagonized by DuP 753 resulting in a pA2 value of 8.48. Responses induced by other agonists, such as norepinephrine and KCl, were not altered. No partial agonistic effect was noted in any of the in vitro assays. In addition, DuP 753 (10(-5) mol/L) had no effect on rabbit lung converting enzyme or rat/human renin activity. These data demonstrate that DuP 753 is a highly potent and specific AII receptor antagonist. DuP 753 represents a useful experimental tool for dissecting the role of the renin-angiotensin system.

Investigation of the antispasmodic potential of Hibiscus sabdariffa calyces

Addition of an aqueous extract of Hibiscus sabdariffa calyces (2.5 ml bath ≈ 125 mg of starting crude material) inhibited the tone of various isolated muscle preparations (rabbit aortic strip, rhythmically contracting rat uterus, guinea-pig tracheal chain and rat diaphragm). Other muscles were stimulated (quiescent rat uterus and frog rectus abdominis). Intravenous injection of the extract to anaesthetized cats lowered the blood pressure in a dose-response manner. The inhibitory effects were resistant to a number of standard receptor blockers but the hypotensive influence was partially blocked by atropine and the tonic effects on rat uterus were partially reduced by hydrocortisone and indomethacin.

Method of removal of aortic endothelium affects arachidonic acid metabolism and vascular reactivity

To assess endothelium-dependent responses of blood vessels in vitro, endothelial cells are removed by a variety of mechanical means. We sought to determine if the method of removal of the endothelium affected arachidonic acid metabolism and vascular reactivity of isolated strips of rabbit aorta. Thoracic aorta of New Zealand White rabbits were excised and sectioned into strips with a sharp razor blade. The luminal surface of the vessel was then gently stroked (denuded-1) or forcefully rubbed (denuded-2) with a moist cotton swab. Vessels were then either fixed in 3% glutaraldehyde and processed for electron microscopy, incubated with [ 14C]arachidonic acid and 20 μM A23187 for determination of arachidonic acid metabolism, incubated with 20 μM A23187 for measurement of endogenous release of 6-keto-prostaglandin F 1 α (6-keto-PGF 1 α ) and 12-hydroxyeicosatetraenoic acid (12-HETE) by specific radioimmunoassays or suspended in an organ chamber filled with Krebs bicarbonate solution for vascular reactivity experiments. Electron micrographs showed that denuded-1 vessels lacked an endothelial cell layer and had slight degeneration of the smooth muscle cells. Additionally, these vessels had a diminished capacity to produce 6-keto-PGF 1 α as compared to control vessels (214 ± 25 vs. 360 ± 36 pg/mg of tissue, P < 0.05). Denuded-2 vessels contained severe degereration and rupture of smooth muscle cells in addition to the loss of the endothelial cell layer. While the 6-keto-PGF 1 α concentration (168 ± 23 pg/mg) was less in denuded-2 vessels, HPLC indicated that the production of [ 14C 12-HETE was markedly increased in these vessels as compared to control or denuded-1 vessels. Specific radioimmunoassays detected enhanced release of 12-HETE in denuded-2 vessels (13 ± 5 pg/mg) as compared to control (6 ± 2 pg/mg) or denuded-1 (6 ± 2 pg/mg) vessels. KCI-induced contractions were significantly less in denuded-2 (2.5 ± 0.3 g) than in control vessels (3.9 ± 0.3 g). Both denuded-1 and denuded-2 vessels contracted similarly to a range of concentrations of norepinephrine but significantly less than did control vessels. Control vessels relaxed to methacholine with an EC 50 of 2 × 10 −7 M. Neither denuded-1 nor denuded-2 vessels relaxed to methacholine. However, vessels in each of the three groups relaxed similarly to sodium nitroprusside EC 50 = 5 × 10 −7 M) . We conclude that some methods of endothelial cell removal may damage smooth muscle cells, increase release of 12-HETE and reduce vascular reactivity.

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.

The source of ca2+ for the spasmolytic actions of longicaudatine, a bisindole alkaloid isolated fromStrychnos trinervis (Vell.) Mart. (Loganiaceae)

Longicaudatine, a tertiary bisindole alkaloid isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), antagonized in a noncompetitive manner, carbachol and histamine induced contractions of the guinea-pig ileum and bradykinin responses in the rat uterus. The respective pD2' values (mean ± SE) were 4.61 ± 0.21, 4.98 ± 0.04 and 4.49 ± 0.01. Longicaudatine, unlike verapamil, had no effect on voltage dependent Ca2+ channels, as it failed to inhibit KCI or CaCl2 induced contractions of guinea-pig ileum and depolarized rat uterus respectively. When compared with sodium nitroprusside, an antagonist of receptor operated Ca2+ channels, longicaudatine produced a slower and weaker inhibition of noradrenaline induced sustained contractions of rabbit aortic strips. However, in the aorta, the alkaloid antagonized the intracellular calcium dependent transient contractions of noradrenaline and longicaudatine (IC50, 5.01 × 10−7 M) was approximately 133 times more potent that procaine (IC50, 6.68 × 10−5 M), a known inhibitor of the release of Ca2+ from intracellular stores. Longicaudatine may exert nonspecific spasmolytic effects by acting on intracellular Ca2+ stores, rather than on depolarization dependent or receptor operated Ca2+ channels.

Differences between the effects of cromakalim and nifedipine on agonist‐induced responses in rabbit aorta

1. The effects of cromakalim on endothelium-denuded rabbit aortic strips were compared with those of the calcium (Ca2+) entry blocking agent, nifedipine. 2. Pre-incubation with cromakalim or nifedipine had no significant effect on the initial phasic component of noradrenaline (NA)-induced responses. 3. Cromakalim (0.3-10 microM), but not nifedipine, inhibited the maintained tonic contractions produced by NA. The effects of cromakalim were antagonized by raising extracellular [K+] or by glibenclamide. 4. Nifedipine inhibited contractions produced by KCl (40 mM) whereas cromakalim had no effect. 5. In Ca2(+)-free physiological salt solution (PSS), cromakalim produced a significant inhibition of both the refilling of and the release of Ca2+ from NA-releasable Ca2+ stores, whereas nifedipine was ineffective. 6. In tissues preloaded with 42K+ cromakalim (0.3-10 microM) produced a concentration-dependent increase in the 42K+ efflux rate coefficient. NA (0.3 microM) also produced an increase in the rate of efflux of 42K+, an effect which was not antagonized by nifedipine (0.3 microM). 7. When microelectrodes were used, cromakalim (1-10 microM) produced a maintained concentration-dependent membrane hyperpolarization. However, low concentrations of cromakalim (less than 1 microM) which relaxed the aorta had no effect on membrane potential. NA had no significant effect on membrane potential. 9. It is concluded that the ability of cromakalim to relax NA-induced contractions in rabbit aorta is not exerted by the indirect closure of nifedipine-sensitive Ca2+ channels. Instead, cromakalim may exert a direct inhibitory action on Ca2+ uptake into and release from Ca2+ stores and additionally inhibit the pathway through which Ca2+ passes from the extracellular fluid to intracellular Ca2+ stores.

Effects of glibenclamide on cytosolic calcium concentrations and on contraction of the rabbit aorta

1. Using fluorometry of fura-2 and rabbit aortic strips, we studied the effects of glibenclamide (GLB), a sulphonylurea anti-diabetic drug and an inhibitor of opening of K+ channels, on cytosolic calcium concentrations ([Ca2+]i) and on force development. 2. Both high K(+)-depolarization and noradrenaline (NA) increased [Ca2+]i and force, in a concentration-dependent manner, in the presence of extracellular Ca2+ (1.25 mM). However, force development in relation to [Ca2+]i ([Ca2+]i-force relationship) observed with NA was much greater than that observed with K(+)-depolarization. 3. Pretreatment with GLB (10(-6)-10(-4) M) for 10 min partially inhibited, in a concentration-dependent manner, both [Ca2+]i elevation and the force development induced by 118 mM K(+)-depolarization or NA 10(-5) M in the presence of extracellular Ca2+. The [Ca2+]i-force relationship induced by both 118 mM K+ physiological salt solutions and by NA 10(-5) M in the GLB-treated strips overlapped that obtained in the non-treated strips, thereby suggesting that GLB has no effect on the Ca2(+)-sensitivity of the intracellular contractile apparatus. Only high concentrations (10(-4) M) of GLB decreased [Ca2+]i and the force, when applied after the force induced by 118 mM K+ PSS or NA 10(-5) M reached the maximum level. 4. In the absence of extracellular Ca2+, NA induced a transient increase in [Ca2+]i and in the force and these increases were inhibited when the vascular strips were pretreated with GLB for 10 min. The [Ca2+]i-force relationship obtained in the GLB-treated strips overlapped that in the non-treated ones. 5. An ATP-sensitive K+ channel opener, cromakalim (10-5M) reduced the increased [Ca2 + ]i and force induced by 25mm K+-depolarization and NA 10-SM. Subsequent application of GLB concentrationdependently reversed this relaxant effect of cromakalim on the NA-induced contraction (IC50 = 2x 10 7 M). Complete reversal of the effect was observed with 10IsM GLB. 6. We suggest that GLB inhibits both high K+-depolarization- and NA-induced contraction of the rabbit aorta, by decreasing [Ca2+]i and with no effect on the [Ca2+]i-force relationship. However, when NA-induced contractions were inhibited by a K+-channel opener, GLB reversed this inhibitory effect by inhibiting K+-channel opening and increasing [Ca2 +].

Anti-5-hydroxytryptamine3 effect of galanolactone, diterpenoid isolated from ginger.

It has been reported that an acetone extract of ginger and its fractions have anti-5-HT (5-hydroxytryptamine; serotonin) effects. In the present study, guinea pig ileum, rat stomach fundus and rabbit aortic strips are used in order to determine the constituents of fraction 2 which are responsible for anti-5-HT effect and to examine their pharmacological properties. The analysis of fraction 2-3 indicated that galanolactone, a diterpenoid, is one of the active constituents. In guinea pig ileum, galanolactone inhibited contractile responses to 5-HT with a pIC50 value 4.93. pIC50 value of galanolactone against the response to 2-methyl-5-HT, a selective 5-HT3 agonist, in the presence of methysergide at 1 x 10(-5) M was 5.10. pIC50 values of ICS 205-930, a selective 5-HT3 antagonist, were 5.30 and 7.49, respectively. The concentration-response curve of 5-HT was shown as a biphasic curve and galanolactone caused a selective shift to the right of the second phase. In the same preparations, the pIC50 value of galanolactone and ICS 205-930 against the response to carbamylcholine (CCh) was 4.45 and 4.46. The inhibitory effect of galanolactone on the 5-HT response in the stomach fundus and aortic strips was less than that in the ileum. In addition, in the thoracic aorta precontracted with 50 mM K+, the relaxing effect of galanolactone was about 1/10 of that of papaverine. These results suggest that the anti-5-HT effect of galanolactone, a diterpenoid isolated from ginger, is related to antagonism of 5-HT3 receptors.

Inhibitory effect of the endothelium on thrombin-induced contraction in rabbit aorta

1. Thrombin caused a tonic contractile response in rabbit aortic strips which showed tachyphylaxis. 2. Thrombin-induced contraction was partially dependent upon extracellular calcium. 3. Contractile response by lower concentrations of thrombin was suppressed by the endothelium. This endothelial effect was blocked by methylene blue, hemoglobin, bromophenacyl bromide or removal of extracellular calcium but not by indomethacin, nordihydroguaiaretic acid or nifedipine. 4. Cyclic GMP levels were not different between the thrombin-stimulated and control strips. 5. Thrombin could not stimulate prostacyclin release from the aortic strips. 6. These results suggest that thrombin possesses a contractile action in rabbit aortic smooth muscle which is attenuated by endothelium-derived relaxing factor (EDRF) spontaneously released from the endothelium during the contraction.

A pharmacological and biochemical examination of AHR-16462B, a novel calcium antagonist coronary vasodilator/antihypertensive

A series of pharmacological and biochemical studies were conducted to characterize AHR-16462B 4-[bis(4-fluorophenyl)methyl]-1-(2-naphthalenylmethyl)piperidine (HCI), a novel antagonist of voltage-sensitive calcium channels. AHR-16462B displaced [3H]-nimodipine binding from calcium channels on rabbit skeletal muscle membranes (IC50 = 118 nM) and inhibited depolarization-induced changes in intracellular free calcium in cultured PC-12 cells (IC50 = 125 nM), but had virtually no effects on binding of specific radioligands to 5-HT1a, 5-HT2, alpha1, alpha2, dopamine2, beta1, beta2, muscarinic M1, or histamine H1 receptors. AHR-16462B antagonized CaCI2-induced contractions of depolarized rabbit aortic strips (pA2 = 8.83), but had no negative chronotropic, and only slight negative inotropic effects on isolated guinea pig atria. In anesthetized dogs, cumulative doses of 0.1, 0.4, and 1.4 mg/kg, i. v., AHR-16462B decreased coronary vascular resistance and blood pressure; the magnitude and duration of these effects were dose related. Heart rate and Lead 2 ECG waveforms remained unaltered at all doses. In conscious spontaneously hypertensive rats (SHR), 3 to 100 mg/kg, p. o., AHR-16462B produced marked, long-lasting, and dose-related antihypertensive actions. Heart rate remained unaltered following 3, 10, and 30 mg/kg AHR-16462B, and bradycardia was evoked by 100 mg/kg. Effective antihypertensive doses of AHR-16462B had modest natriuretic and/or chloruretic actions.

Comparison of isobutyl nitrate and isobutyl nitrite: tolerance and cross-tolerance to glyceryl trinitrate

This study includes the first systematic comparison of an organic nitrate with the corresponding organic nitrite - isobutyl nitrate and isobutyl nitrite. The spasmolytic activity of the nitrite on isolated rabbit aortic strips was stronger, more rapid in onset, but less stable than the activity of the nitrate. In vitro tolerance to glyceryl trinitrate and isobutyl nitrite greatly weakened the activity of isobutyl nitrate, respectively, but had much less effect on isobutyl nitrite. Possible reasons for these differences are discussed.

The dualistic mode of action of the vasodilator drug, nicorandil, differentiated by glibenclamide in 86Rb flux studies in rabbit isolated vascular smooth muscle

(1) In rabbit isolated aorta, the effects of the antianginal drug, nicorandil, of the K+ channel opener, cromakalim, and of the nitrovasodilator, sodium nitroprusside, on 86Rb efflux and on contractile force were compared. (2) In ion flux studies using 86Rb as a marker of K+ ions, both nicorandil and cromakalim, but not sodium nitroprusside, increased the efflux of 86Rb in non-stimulated preparations. The increase of membrane K+ conductance induced by nicorandil and cromakalim was totally suppressed by 10(-5) mol/l of the sulfonylurea derivative, glibenclamide. (3) The vasoconstrictor drug, noradrenaline (3 x 10(-7) mol/l), effectively increased the rate of 86Rb efflux. This stimulatory response was unaffected by glibenclamide, but was totally inhibited by Ca2+ depletion suggesting that the activation of Ca2(+)-sensitive K+ channels was responsible for this action of noradrenaline. (4) Sodium nitroprusside and nicorandil, the latter in the presence of glibenclamide to suppress the glibenclamide-sensitive stimulatory component on 86Rb efflux, antagonized the noradrenaline-induced increase in 86Rb efflux, while cromakalim in the presence of glibenclamide had no effect. (5) All of the vasodilators relaxed rabbit aortic strips contracted by 10(-7) mol/l noradrenaline in a concentration-dependent manner. (6) The vasodilatory response to cromakalim was antagonized by glibenclamide, whereas the relaxant action of nicorandil and of sodium nitroprusside remained unaffected. (7) These results demonstrate that under particular experimental circumstances, nicorandil can behave in vascular smooth muscle both as an opener of glibenclamide-sensitive K+ channels, and as a directly acting nitrovasodilator which acts via reduction of cellular calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)

L-Glutamine inhibits the release of endothelium-derived relaxing factor from the rabbit aorta

The present study investigates the effect of the amino acid L-glutamine (L-Gln) on the release of endothelium-derived relaxing factor (EDRF) from the luminally perfused rabbit aorta and on endothelium-dependent relaxations of rabbit aortic strips. L-Gln (200 microM) had no effect on the acetylcholine (Ach)-induced release of EDRF from freshly prepared aortic tissues. The concentration of L-arginine (L-Arg) in endothelial cells isolated from these aortae was approximately 4 mM, as determined by HPLC analysis. After an initial equilibration period of 2 h and two consecutive infusions of Ach (55 microM for 15 min) at 2 and 3 h, L-Arg levels fell by 62 +/- 14% (n = 4). Under these conditions, L-Gln (200 microM) but not D-Gln (200 microM) inhibited the release of EDRF by 50 +/- 4% (n = 7). This effect of L-Gln was partially reversed by infusions of L-Arg (500 microM) but not D-Arg (500 microM). L-Gln (200 microM) but not D-Gln (200 microM) potentiated the inhibitory effect of N omega-nitro-L-arginine (30 microM), an inhibitor of EDRF biosynthesis, on Ach-induced relaxations of rabbit aortic strips, whereas L-Gln alone had no effect. Thus, L-Gln inhibits the release of EDRF from intact blood vessels presumably by interfering with the generation of L-Arg by the endothelium.

Dual action of amphetamine on the rabbit aortic strips

Dual action of amphetamine on the rabbit aortic strips

Different time course of atrial natriuretic factor-induced relaxation in rabbit aorta and portal vein

Atrial natriuretic factor (ANF) and nitroglycerine were tested in superfused rabbit aorta and portal vein strips precontracted with norepinephrine. The ANF dose-response curves were similar in both tissues, however, relaxation was fast and transient in portal veins whereas it was sustained and of slow onset in aortas. Nitroglycerine was more potent in portal veins than in aortas but relaxation was fast and transient in both tissues. The results suggest that the time course of ANF-induced relaxation in different vessels may be of relevance to the overall hemodynamic profile of this peptide in intact animals.

Biotransformation of Glyceryl Trinitrate and Elevation of Cyclic GMP Precede Glyceryl Trinitrate-Induced Vasodilation

In this study, we examined glyceryl trinitrate (GTN) biotransformation and cyclic GMP elevation in vascular smooth muscle before onset of GTN-induced relaxation. Isolated rabbit aortic strips (RAS) and strips of bovine pulmonary artery (BPA) and bovine pulmonary vein (BPV) were contracted submaximally and incubated with [3H]GTN. Before onset of GTN-induced vasodilation, the tissues were freeze-clamped and then analyzed for GTN, glyceryl-1,2-dinitrate (1,2-GDN), and glyceryl-1,3-dinitrate (1,3-GDN) and for cyclic GMP. Before onset of relaxation of RAS, BPA, and BPV, there was significant biotransformation of GTN to GDN and significant elevation of cyclic GMP. There was significantly greater biotransformation of GTN and elevation of cyclic GMP by BPV than by BPA incubated with the same concentration of GTN, which was temporally related with the more rapid onset of relaxation induced in BPV than in BPA. These results are consistent with the hypothesis that the magnitude of GTN biotransformation before vasodilation is the important determinant of subsequent tissue relaxation. In GTN biotransformation before vasodilation, there was preferential formation of 1,2-GDN. These data indicate that the mechanism of GTN biotransformation to 1,2-GDN is related to elevation of cyclic GMP and subsequent vasodilation.

Serum-induced proliferation of rabbit aortic smooth muscle cells from the contractile state is inhibited by 8-Br-CAMP but not 8-Br-cGMP

A method is described for the quantification of vascular smooth muscle cell growth from individual explants of contractile rabbit aortic tunica media. The precision of the method probably depends on regular explant geometry (1-mm squares) and pooling sufficient explants. Serum-induced growth was quantified by measurements of ATP concentration, incorporation of [ 3H]thymidine and DNA concentration. The possible effects of endogenous vasodilator agents on growth were investigated by using lipid soluble analogues of their second messengers, namely 8-Br-cAMP and 8-Br-cGMP, which are known to relax rabbit aortic strips. Cell growth was inhibited concentration-dependently by 8-Br-cAMP but not 8-Br-cGMP (0.01-1 mM). The effect of 8-Br-cAMP was reversible, and also occurred when addition was delayed until after growth had commenced. The results imply that endogenous vasodilators such as prostacyclin, adenosine and adrenaline, which increase cAMP concentration, may normally suppress smooth muscle cell growth, whereas nitric oxide and atriopeptins, which increase cGMP concentration, may not.

INHIBITION OF ENDOTHELIAL NITRIC OXIDE BIOSYNTHESIS BY N‐NITRO‐l‐ARGININE

1. The actions of N-nitro-L-arginine (NOLA) on the release of nitric oxide (NO) from arterial endothelial cells was studied in rat isolated thoracic aortic rings and by bioassay of NO derived from cultured bovine aortic endothelial cells. 2. NOLA (3-10 mumol/L) caused concentration-dependent inhibition of acetylcholine-induced relaxation of phenylephrine-contracted rat aortic rings, which is dependent on the release of NO from the endothelium. The inhibitory actions of NOLA could be prevented by pre- and co-incubation with L-arginine (1 mmol/L). 3. Endothelium-independent relaxation induced by sodium nitroprusside was not affected by NOLA. 4. The release of NO from bovine aortic endothelial cells, induced by bradykinin (10 nmol/L), was detected by bioassay on pre-contracted rabbit aortic strips. NOLA (1-3 mumol/L, given through the cell column) reduced or abolished the release of NO, but did not affect relaxations of the bioassay tissues induced by glyceryl trinitrate or authentic NO. 5. These data indicate that NOLA potently inhibits the biosynthesis of NO from L-arginine, and thus prevents its release from arterial endothelial cells. It may be a useful pharmacological tool for probing the significance of NO biosynthesis in cardiovascular function.

A new kalium channel blocker of Chinese medicinal origin —Benzyltetrahydropalmatine hydrochloride

Benzyltetrahydropalmatine hydrochloride (BTHP) exhibited antiarrhythmic action in animal models. I. Electrophysiological effects of BTHP were investigated in various heart preparations. 1) BTHP markedly prolonged functional refractory period and inhibited adrenaline-induced automaticity. It decreased spontaneously beating rate of right atrium and abolished ouabain-induced delayed afterdepolarization and triggered activity of papillary muscle. 2) In standard microelectrode and contractility experiments BTHP concentration-dependently prolonged the action potential duration (APD) and effective refractory period (FRP) between 1-100 mumol/L; the force of contraction remained unchanged. 3) In voltage clamp experiments BTHP 1-100 mumol/L inhibited in dose-dependent manner the Ik with IC50 of 13 mumol/L and inhibited also Is at high concentration. 4) In monophasic action potential (MAP) of feline ventricle MAPD50 and MAPD90 were prolonged by BTHP in normal myocardium, and shortened APD induced by ischemia and reperfusion was restored to normal level. 5) In ECG and His-bundle electrogram heart rate was reduced; P-R and A-H interval were prolonged, but H-V interval and V duration were unaffected. II. BTHP showed a competitive alpha 1-adrenoceptor-blocking effect with pA2 value of 5.8 and 5.86 in rat anococcygeus muscle and rabbit aortic strips respectively. Radioligand binding assays showed that BTHP had affinity for both alpha 1 and alpha 2-adrenoceptor. The results from these experiments show that BTHP is a new K+ channel blocker of Chinese medicinal origin with alpha 1-adrenoceptor-blocking action.

Bacitracin U.S.P. contains a factor that stimulates receptors for 5-hydroxytryptamine on rabbit aortic strips

Bactracin (BAC) U.S.P., obtained in the form of sterile powder, elicits dose-dependent and non-tachyphylactic contractions of the rabbit isolated aorta and of other rabbit vessels. The use of several pharmacologic antagonists suggests that BAC is a 5-hydroxytryptamine mimetic in aortic strips, since the antibiotic is competitively antagonized by methysergide and ketanserin with pA 2 values compatible with an agonist action on the 5-HT 2 receptors found in the aortic preparation. It remains to be determined whether bacitracin A, the chief constituent of BAC U.S.P., is the 5-HT agonist.