Effect of propofol on human fetal placental circulation.

BACKGROUND: Propofol is an alternative to thiopental for induction of general anaesthesia for cesarean section. It crosses the placenta and induces vasodilatation of isolated vessels and may therefore alter fetal placental vascular resistance. The direct effect of propofol on the fetal placental circulation was studied in vitro. The actions of propofol on vasoconstrictive effects induced by angiotensin II (Ang II), bradykinin (BK), prostaglandin F(2alpha) (PGF(2alpha)) and potassium chloride (KCl) were evaluated. METHODS: Full-term healthy human placentas (n=48) were perfused with modified Tyrode's solution using a pulsatile pump. Placental perfusion pressure was measured in response to injection of Ang II, BK, KCl and PGF(2alpha) before and after perfusion with propofol (1.7 x 10(-5) and 5.6 x 10(-5) M). RESULTS: BK, Ang II, KCl and PGF(2alpha) induced a dose-dependent increase in placental perfusion pressure. Propofol induced a concentration-dependent decrease in placental perfusion pressure, but this was not observed with the propofol solvent (Intralipid). Propofol, but not Intralipid, reduced the vasoconstrictor effects of BK, KCl and PGF(2alpha), while the effect of Ang II was not changed. The effect of KCl was abolished in placentas perfused with Ca(2+)-free solution, while the effect of Ang II was not altered. CONCLUSIONS: Propofol induced vasodilatation and inhibited the vasoconstrictive effects of BK and PGF(2alpha), in the human placenta. These findings suggest that propofol may not reduce fetal placental blood flow. Since propofol reduced the vasoconstricting effect of KCl but not that of AngII, we propose that the vasodilatory effect of propofol in the human placenta involves inhibition of Ca(2+) channels.

Angiotensin II-mediated vasodilation is reduced in adult spontaneously hypertensive rats despite enhanced expression of AT2 receptors.

1. The vasodilator action of angiotensin (Ang) II has not yet been demonstrated in spontaneously hypertensive rats (SHR), nor have any possible changes in this response during the development of hypertension. 2. In the present study, the vasodilator effect of AngII was evaluated in the rat isolated, preconstricted mesenteric arterial bed (MAB) from 6- (young) and 24-week-old (adult) SHR and compared with effects on MAB from age-matched normotensive rats (control). 3. Angiotensin II (10-300 nmol) induced vasodilation in noradrenaline (NA)-preconstricted MAB that was greater in vessels from young compared with adult rats in both the control and SHR groups. Angiotensin II-induced vasodilation was reduced by the angiotensin AT(2) receptor antagonist PD 123319 (10 micromol/L), the angiotensin-(1-7) receptor antagonist A779 (1 micromol/L) and the bradykinin B(2) receptor antagonist HOE-140 (0.01 micromol/L), but not by the AT(1) receptor antagonist losartan (30 micromol/L). Expression of AT(2) receptors was weak in vessels from adult control rats compared with that in young control rats, whereas in young SHR AT(2) receptor expression was increased compared with that in young control rats. This increased expression of AT(2) receptors was maintained in adult SHR and there was no significant difference in AT(2) receptor expression between young and old SHR. 4. The findings of the present suggest that AngII induces an AT(2) receptor-mediated vasodilator effect in the MAB via activation of angiotensin-(1-7) and bradykinin receptors, an action that is reduced in adult control rats and adult SHR. In adult control rats, the attenuated response of AngII is probably due to endothelial dysfunction and reduced expression of AT(2) receptors, whereas in adult SHR it is associated with endothelial dysfunction alone. Increased expression of AT(2) receptors in SHR may represent a counteracting response for modulating blood pressure.

The role of NO-cGMP pathway and potassium channels on the relaxation induced by clonidine in the rat mesenteric arterial bed.

The mechanisms involved in the vasodilation action of clonidine have not yet been completely elucidated. We investigated the potential mechanisms that seem to be involved in the clonidine vasodilator effect using rat isolated mesenteric arterial bed (MAB). In precontracted MAB, clonidine (10-300 pmol) induced a dose-dependent relaxation, that was inhibited by endothelium removal (deoxycholic acid - 2.5 mM) and reduced by the alpha(2) adrenoceptor inhibitors yohimbine (1-3 microM) and rauwolscine (1 microM). The endothelium-dependent vasodilation induced by clonidine was reduced by the nitric oxide (NO) synthase inhibitor L-NAME (0.3 mM) and guanylyl cyclase inhibitor ODQ (10 microM) but was not affected by indomethacin (3-10 microM) alone. High K+ (25 mM) solution reduced the vasodilator effect of clonidine that was further attenuated by L-NAME. In the presence of high K+ plus L-NAME, the residual vasodilator effect of clonidine was further reduced by indomethacin (3 microM). The Ca(2+)-dependent K+ channel (K+(Ca2+)) inhibitors, charybdotoxin (ChTx; 0.1 microM) plus apamin (0.1 microM), also reduced the vasodilation induced by clonidine, however this response was not further reduced in the presence of L-NAME as observed with acetylcholine (10 pmol). In the presence of ATP-dependent K+ channel (K+(ATP)) blocker, glibenclamide (10 microM), the inhibitory effect of ChTx plus apamin plus L-NAME was increased. In contrast, the vasodilation induced by clonidine was not affected by voltage-dependent K+ channels (K(V)) blocker, 4-aminopyridine (4-AP, 1 mM). In conclusion, our results demonstrate that clonidine activates alpha(2)-adrenoceptors in rat MAB and that the endothelium-dependent vasodilation is mediated by activation of NO-cGMP pathway, hyperpolarization due to activation of K+(Ca) and K+(ATP) channels. Prostaglandins might participate in the vasodilator effect of clonidine when NO and EDHF mechanisms are blunted.

Endothelium-dependent vasodilator effect of Euterpe oleracea Mart. (Açaí) extracts in mesenteric vascular bed of the rat.

Açai (Euterpe oleracea Mart.) a fruit from the Amazon region, largely consumed in Brazil is rich in polyphenols. Experiments were undertaken to determine whether hydro-alcoholic extract obtained from stone of açaí induces a vasodilator effect in the rat mesenteric vascular bed precontracted with norepinephrine (NE) and, if so, to elucidate the underlying mechanism. Açai stone extract (ASE, 0.3-100 microg) induced a long-lasting endothelium-dependent vasodilation that was significantly reduced by N(G)-nitro-l-arginine methyl ester (l-NAME) and (1)H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-l-one (ODQ) and abolished by KCl (45 mM) plus l-NAME. In vessels precontrated with NE and KCl (45 mM) or treated with K(Ca)(+2) channel blockers (charybdotoxin plus apamin), the effect of ASE was significantly reduced. However this effect is not affect by indomethacin, glybenclamide and 4-aminopiridine. Atropine, pyrilamine, yohimbine and HOE 140 significantly reduced the vasodilator effect of acetylcholine, histamine, clonidine and bradykinin, respectively, but did not change the vasodilator effect of ASE. In cultured endothelial cells ASE (100 microg/mL) induced the formation of NO that was reduced by N(G)-nitro-l-arginine (l-NA, 100 microM). The present study demonstrates that the vasodilator effect of ASE is dependent on activation of NO-cGMP pathway and may also involve endothelium-derived hyperpolarizing factor (EDHF) release. The vasodilator effect suggest a possibility to use ASE as a medicinal plant, in the treatment of cardiovascular diseases.

Inhibition of l-arginine transport in platelets by asymmetric dimethylarginine and N-monomethyl-l-arginine: effects of arterial hypertension.

Nitric oxide (NO) produced by human platelets plays an important role in all stages of platelet activation. l-Arginine, the precursor for NO synthesis, modulates NO production by platelets. The l-arginine analogues asymmetric dimethylarginine (ADMA) and N(G)-monomethyl-l-arginine (l-NMMA) are endogenous inhibitors of nitric oxide synthase (NOS), involved in the physiopathology of arterial hypertension. The aim of the present study was to investigate the inhibitory effects of endogenous and exogenous l-arginine analogues on l-arginine influx in platelets from healthy controls and hypertensive patients. Twelve patients with uncomplicated essential hypertension (stage I) and 15 age-matched normotensive controls participated in the present study. Platelets were isolated and incubated with l-[(3)H]-arginine and increasing concentrations of l-arginine analogues (5-2000 micromol/L). The influx of l-arginine was inhibited in a concentration-dependent manner by l-NMMA in platelets from controls (K(i) = 42 +/- 6 micromol/L) and this inhibitory effect was markedly higher in hypertensive platelets (K(i) = 23 +/- 4 micromol/L). Similarly, the K(i) for ADMA inhibition of l-arginine transport was significantly more pronounced in platelets from hypertensive patients (K(i) = 16 +/- 1 micromol/L) compared with controls (K(i) = 27 +/- 2 micromol/L). In contrast, N(G)-nitro-l-arginine methyl ester (l-NAME) was found to be a weak inhibitor of l-arginine influx in platelets from controls (K(i) = 1917 +/- 319 micromol/L) and hypertensive patients (K(i) = 2279 +/- 578 micromol/L). Aminoguanidine, a selective inhibitor of inducible NOS, failed to inhibit l-arginine transport. Our findings provide the first evidence that ADMA and l-NMMA markedly inhibit l-arginine transport in human platelets, an effect that is more pronounced in hypertensive patients. It is possible that endogenous l-arginine analogues, by inhibiting NO synthesis, are involved in the platelet activation present in hypertension.

Genotoxic evaluation of a vinifera skin extract that present pharmacological activities.

Toxicity of an alcohol-free hydro-alcoholic grape skin extract (GSE) obtained from red grapes Vitis labrusca (Isabel varietal) that present antihypertensive, vasodilator and antioxidant effects was estimated by different bioassays. Using the Salmonella/microsome assay for strains TA97, TA98, TA100 and TA102 no mutagenicity was detected for all tested concentrations (0.1-100 microg/ml), even with metabolization. Nevertheless, cytotoxicity was observed for TA97 and TA102 with and without metabolization and for TA100 with metabolization. The measurement of beta-galactosidase induction in the SOS-chromotest was positive only for Escherichia coli PQ37 when metabolization enzymes were present. Using Balb/c 3T3 fibroblasts, DNA strand breaks induction by GSE was also investigated by the comet assay and no significative difference was detected for treated and no treated DNA for 60 min. Our data suggest that GSE although no mutagenic presents cytotoxic activity.

The role of bradykinin, AT2 and angiotensin 1-7 receptors in the EDRF-dependent vasodilator effect of angiotensin II on the isolated mesenteric vascular bed of the rat.

1. The mechanisms involved in the vasodilator actions of angiotensin II (Ang II) have not yet been completely elucidated. We investigated the potential mechanisms that seem to be involved in the Ang II vasodilator effect using rat isolated mesenteric vascular bed (MVB). 2. Under basal conditions, Ang II does not affect the perfusion pressure of MVB. However, in vessels precontracted with norepinephrine, Ang II induces vasodilation followed by vasoconstriction. Vasoconstrictor, but not the vasodilation of Ang II, is inhibited by AT(1) antagonist (losartan). The vasodilator effect of Ang II was not inhibited by AT(2), angiotensin IV and angiotensin 1-7 receptor antagonists alone (PD 123319, divalinal, A 779, respectively). 3. The vasodilator effect of Ang II is significantly reduced by endothelial removal (deoxycholic acid), but not by indomethacin. Inhibition of NO-synthase by N(G)-nitro-l-arginine methyl ester (l-NAME) and guanylyl cyclase by 1H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-1-one (ODQ) reduces the vasodilator effect of Ang II. This effect is also reduced by tetraethylammonium (TEA) or l-NAME, and a combination of l-NAME plus TEA increases the inhibitory effect of the antagonists alone. However, indomethacin does not change the residual vasodilator effect observed in vessels pretreated with l-NAME plus TEA. 4. In vessels precontracted with norepinephrine and depolarized with KCl 25 mm or treated with Ca(2+)-dependent K(+) channel blockers (charybdotoxin plus apamin), the effect of Ang II was significantly reduced. However, this effect is not affected by ATP and voltage-dependent K(+) channel blockers (glybenclamide and 4-aminopyridine). 5. Inhibition of kininase II with captopril significantly potentiates the vasodilator effect of bradykinin (BK) and Ang II in the rat MVB. The inhibitory effect of the B(2) receptor antagonist HOE 140 on the vasodilator effect of Ang II is further enhanced by PD 123319 and/or A 779. 6. The present findings suggest that BK plays an important role in the endothelium-dependent vasodilator effect of Ang II. Probably, the link between Ang II and BK release is modulated by receptors that bind PD 123319 and A 779.

Antihypertensive, vasodilator and antioxidant effects of a vinifera grape skin extract.

Cumulative evidence suggests that moderate wine consumption exerts a cardioprotective effect. We investigated the occurrence of an antihypertensive effect of an alcohol-free hydroalcoholic grape skin extract (GSE) obtained from skins of a vinifera grape (Vitis labrusca) in experimental rodent hypertension models. The vasodilator effect of GSE (polyphenols concentration 55.5 mg g(-1)) was also assessed in the isolated mesenteric vascular bed of Wistar rats and the antioxidant effect was studied on lipid peroxidation of hepatic microsomes. Oral administration of GSE significantly reduced systolic, mean and diastolic arterial pressure in Wistar rats with desoxycorticosterone acetate-salt and N(G)-nitro-L-arginine methyl ester (L-NAME) induced experimental hypertension. In the rat isolated mesenteric vascular bed pre-contracted with norepinephrine, bolus injections of GSE induced endothelium-dependent vasodilatation that was substantially inhibited by L-NAME, but not by indometacin, tetraethylammonium or glibenclamide. Lipid peroxidation of hepatic microsomes estimated as malondialdehyde production was concentration-dependently inhibited by GSE. In conclusion, the antihypertensive effect of GSE might be owing to a combination of vasodilator and antioxidant actions of GSE. These findings also suggest that the beneficial effect of moderate red wine consumption could be owing to an antihypertensive action induced by compounds occurring in the skin of vinifera grapes.

Bronchodilator activity of Mikania glomerata Sprengel on human bronchi and guinea-pig trachea.

The effects of aqueous extracts and hydro-alcoholic extract (HAE), and of a dichloromethane fraction (MG1) obtained from the HAE of Mikania glomerata leaves on isolated respiratory and vascular smooth muscle have been investigated. Aqueousextracts and HAE induced a significant inhibition on the histamine contractions on the isolated guinea-pig trachea. HAE extract induced a concentration-dependent relaxation on guinea-pig trachea pre-contracted with histamine (IC50 0.34 (0.29-0.39) mg mL(-1)), acetylcholine (IC50 0.72 (0.67-0.77) mg mL(-1)) or K+ (IC50 1.41 (1.18-1.64) mg mL(-1)) and on isolated human bronchi precontracted with K+ (IC50 0.34 (0.26-0.42) mg mL(-1)). The dichloromethane fraction induced a concentration dependent relaxation in guinea-pig trachea precontracted with K+ (IC50 0.017 (0.012-0.022) mg mL(-1)). The dichloromethane fraction had also a small vasodilator effect on the isolated mesenteric vascular bed and on the isolated rat aorta, and a significant reduction of the oedema induced by subplantar injections of Bothropsjararaca venom in mice. When tested on plasmid DNA, MG1 did not damage the DNA. Chromatographic analysis showed the presence of 11.4% w/w coumarin in MG1. The results supported the indication of M. glomerata products for the treatment of respiratory diseases where bronchoconstriction is present.

The effects of nitric oxide synthase inhibitors on the sedative effect of clonidine.

UNLABELLED: The mechanism underlying the Niteroi, Rio de Janeiro sedative effect of clonidine, an alpha2-adrenoceptor agonist, remains uncertain. Because activation of alpha2-adrenoceptors induces release of nitric oxide (NO), we tested the hypothesis that the sedative effect of clonidine depends on NO-related mechanisms. The effect of 7-nitro indazole on the sleeping time induced by clonidine was studied in Wistar rats. In addition, we examined the effect of clonidine, alpha-methyldopa, and midazolam on the thiopental-induced sleeping time in rats pretreated with N(G)-nitro-L-arginine-methyl-ester (L-NAME). The sleeping time induced by clonidine was significantly decreased by 7-nitro indazole. Thiopental sleeping time was increased by clonidine, alpha-methyldopa, and midazolam. L-NAME reduced the prolongation effect of clonidine and alpha-methyldopa, but did not alter the effect of midazolam on the thiopental-induced sleeping time. The inhibitory effect of L-NAME on clonidine-dependent prolongation of thiopental-induced sleeping time was reversed by L-arginine. These results suggest that NO-dependent mechanisms are involved in the sedative effect of clonidine. In addition, this effect seems to be specific for the sedative action of alpha2-adrenoceptors agonists. IMPLICATIONS: Clonidine, an antihypertensive drug, is also a sedative. This sedative effect, although an adverse event in the treatment of hypertensive patients, can be helpful for sedation of surgical patients. The mechanism of this effect, however, is unknown. In this study, we show that the sedative effect of clonidine is mediated by nitric oxide, because it could be prevented by pretreatment with nitric oxide synthase inhibitors.

Actions of L-NAME and methylene blue on the hypotensive effects of clonidine and rilmenidine in the anesthetized rat.

The antihypertensive mechanism of alpha2-adrenoceptor agonists, such as clonidine and rilmenidine, is not completely elucidated, although it is probably due to reduction of sympathetic tone mediated by stimulation of central alpha2-adrenoceptors. Because activation of alpha2-adrenoceptors on endothelial cells induces release of endothelium-derived relaxing factor (EDRF), we determined whether nitric oxide (NO) release is involved in the antihypertensive action of clonidine and rilmenidine. In chloralose-anesthetised Wistar rats, systolic and diastolic arterial blood pressures were recorded on a polygraph. Intravenous injection of clonidine or rilmenidine (control group) caused a rapid increase of arterial blood pressure. followed by a long-lasting hypotensive effect. The hypotensive effects, estimated as the area enclosed by the decrease in diastolic pressure during the 20 min after clonidine and rilmenidine injections, were 574+/-60 and 410+/-59 mm Hg/min, respectively. The delta decrease in diastolic arterial blood pressure observed 20 min after intravenous injections of clonidine and rilmenidine was 48+/-5 and 34+/-3 mm Hg, respectively. Clonidine and rilmenidine injected 5-10 min after intravenous pretreatment with L-NAME (2 and 1 mg/kg) or methylene blue (10 mg/kg) induced hypotensive effects that were significantly smaller than that observed for the control group. These results suggest that the antihypertensive effects of clonidine and rilmenidine also may be modulated by the NO-cyclic guanosine monophosphate (cGMP) pathway at the level of the central nervous system and/or at the vascular peripheral circulation.

Pharmacological aspects of mouse hind-paw oedema induced by Lachesis muta rhombeata venom.

Pharmacological aspects of mouse hind-paw oedema induced by subplantar injections of Lachesis muta rhombeata (LMR) venom were investigated. The oedema induced by subplantar injections of 10 to 50 ng/g of LMR venom is dose dependent, with onset, peak and duration at 30, 60 and 180 min, respectively. Subplantar injection of 30 ng/g of Bothrops jararaca (BJ) venom induced oedema that has the same intensity as 30 ng/g of LMR venom but lasts for more than 4 h suggesting different time course. Systemic effects or haemorrhage were not observed with doses less than 50 ng/g. Oedema is not due to the presence of oedematogenic amines since dialysis did not change the oedema induced by 30 ng/g of LMR venom. Part of the oedema induced by LMR venom is due to a thermolabile fraction since pre-heating the venom at 100 degrees C for 15 min induced a significant reduction (56.19 +/- 6.8%) of the oedematogenic activity. The oedema induced by LMR venom is possibly induced by release of a pharmacological active substance at the site of injection. Histamine, arachidonate metabolites, nitric oxide and serotonin may play important roles in the oedematogenic effect of LMR venom since pre-treatment of mice with pyrilamine, indomethacin, dexamethasone, L-NAME and methysergide induced a significant reduction (49.86 +/- 10%; 51.06 +/- 5.9%; 77.66 +/- 3.6%; 73.30 +/- 6.1% and 93.77 +/- 2.8%, respectively) of the oedema formation. The present results demonstrate that the oedema induced by LMR and BJ venoms may be triggered and maintained by different pharmacological mechanisms. Since methysergide and L-NAME were the most active inhibitors of the oedema we can suggest that a link between serotonin release by the venom and a NO synthase activation may be an important step in the oedema formation induced by LMR venom.

Effect of prostacyclin on the perfusion pressure and on the vasoconstrictor response of angiotensin II in the human isolated foetal placental circulation.

The effect of prostacyclin infusion on the perfusion pressure and on the vasoconstrictor response to three doses of angiotensin II was investigated in six full-term human placentas. The placentas were perfused with a modified Krebs-Henseleit solution and placenta perfusion pressure was recorded. Prostacyclin 5 X 10(-8) M, infused through the foetal placental circulation, produced a significant decrease in placental vascular resistance. The vasodepressor effect of prostacyclin persisted throughout the perfusion period and promptly disappeared when the infusion was stopped. The pressor response of angiotensin II was significantly reduced by prostacyclin infusion. These data suggest an interaction between the vascular effects of prostacyclin and angiotensin II on the placental circulation that might be important in the control of foetal placental blood flow.

Schistosoma mansoni: effects of bromolysergic acid diethylamide, verapamil, and Ca2+-free solution on the motor activity of the isolated male worm induced by electrical stimulation and oxamniquine.

Electrical stimulation and oxamniquine effect the motor activity of isolated Schistosoma mansoni. Electrical stimulation produced contractions that increased with stimulus intensity. Oxamniquine (10(-4) M) produced an increase in basal tonus and in the frequency and amplitude of the worm's spontaneous contractions. Incubation in the absence of calcium produced a decrease in the basal tonus, abolished the spontaneous contractions of S. mansoni, and abolished the mechanical response induced by electrical stimulation and oxamniquine. The effects of electrical stimulation and oxamniquine were, respectively, significantly reduced and abolished by 10(-6) M verapamil (a calcium channel blocking agent). Bromolysergic acid diethylamide (3 X 10(-5) M), a serotonin blocking agent, reduced the motor response induced by high intensity electrical stimulation and blocked the response induced by oxamniquine. The effects of low intensity electrical stimulation were not modified in the presence of bromolysergic acid. We think that external Ca2+ is important for basal tonus, for spontaneous motor activity, and for motor responses of S. mansoni induced by electrical stimulation and oxamniquine. Serotonin may be important for mechanical responses induced by high intensity electrical stimulation and for responses induced by oxamniquine.

Schistosoma mansoni: preparation, characterization of (Na+ + K+)ATPase from tegument and carcass.

The preparation and some biochemical properties of a (Na+ + K+)ATPase from male adult Schistosoma mansoni are described. After incubation in a membrane disruption medium, the tegument and carcass of the worms were separated and treated to obtain fractions enriched in (Na+ + K+)ATPase. The activity of the tegumental ouabain sensitive (Na+ + K+)ATPase at 37 C was 20.3 mumole Pi X mg-1 protein X hr-1 and represented 32% of the total ATPase activity. The (Na+ + K+)ATPase prepared from the carcass had a lower specific activity (3.7 mumole Pi X mg-1 protein X hr-1) but a higher relative activity (55%). Similar concentrations of Na+ and K+ activated the enzymes from both sources, and both enzymes were inhibited by similar concentrations of calcium. However, the enzyme from carcass was ten times more sensitive to ouabain than the enzyme from tegument. Comparison with results obtained on the (Na+ + K+)ATPase of human heart showed that the enzymes from the worms were more resistant to ouabain. The half maximal inhibitory concentration of dihydroouabain compared to that of ouabain was also different in the enzymes from human and worm. We conclude that (1) there exists at least one structural difference between the (Na+ + K+)ATPase of S. mansoni and that of the human host, and (2) it is useful to separately study the enzymes from tegument and carcass because they differ in sensitivity to cardiac glycosides.

Effect of captopril on bradykinin inactivation by human foetal placental circulation.

The inactivation of bradykinin on passage across the human foetal placental circulation was investigated in six full-term human placentas. The placentas were perfused with a modified Krebs-Henseleit solution and placenta perfusion pressure was recorded. Samples collected at the arterial inflow and at the venous effluent were assayed on the isolated guinea-pig ileum as an estimation of bradykinin activity. Bradykinin (100 ng ml-1) was infused through the foetal placental vessels before and during captopril 4 X 10(-7) M. Bradykinin produced a transient increase in placental vascular resistance that was not potentiated by captopril. Bradykinin activity was completely abolished after passage through the foetal placental circulation, and the inactivation was blocked by captopril. These data suggest that angiotensin I converting enzyme (kininase II) might occur in the foetal placental vessels.

Effect of terbutaline on the human fetal placental circulation.

The effect of terbutaline, a beta2-adrenoceptor stimulator, on the vascular resistance of isolated human placenta was examined. Terbutaline produced no change in basal placental vascular resistance, but when the placental vessels were constricted with angiotensin, terbutaline produced a graded decrease in vascular resistance. The vasodilating effect of a high dose of terbutaline was smaller than the effect 20 microgram of isoprenaline and the effect was significantly blocked by propranolol, a beta-adrenoceptor antagonist. The results suggest that the vasodilating effect of terbutaline on the fetal placental circulation can play a role in the improvement of fetal condition during treatment of premature labour and intrapartum fetal distress.

Effect of strophantin on the isolated guinea-pig ileum.

The effect of strophantin on isolated guinea-pig ileum was investigated. It was found that strophantin produces a dose-dependent contraction that is not blocked by atropine, ganglionic blockade, but is potentiated by prostigmine. Depolarization of the guinea-pig ileum by a high potassium solution does not change the effect of strophantin. Strophantin response is competitively antagonized by verapamil. The effect is significantly reduced, 5 to 10 min, after the preparation is immersed in zero calcium Tyrode solution. These results support the view that the effect of strophantin is dependent on the influx of calcium through the cell membrane.