Interaction between myometrial relaxants and oxytocin: a comparison between relaxin, cromakalim and salbutamol

1992 ◽  
Vol 135 (1) ◽  
pp. 29-36 ◽  
Author(s):  
S. J. Downing ◽  
M. Hollingsworth
Keyword(s):  
Corn Oil ◽  
Late Pregnancy ◽  
Hormone Treatment ◽  
Treatment Groups ◽  
Uterine Contractions ◽  
Oestradiol Benzoate ◽  
Oxytocin Infusion ◽  
Increased Sensitivity ◽  
Spontaneous Contractions

ABSTRACT The influence of treatment with oestradiol on the effects of the uterine relaxants, relaxin, salbutamol (an agonist at β2-adrenoceptors) and cromakalim (a potassium channel opener) and their interactions with the uterine stimulant oxytocin were investigated in vivo in the ovariectomized rat. Oestradiol benzoate (0·4 μg/kg per day) significantly increased sensitivity to cromakalim as an inhibitor of spontaneous uterine contractions compared with vehicle-treated rats by approximately threefold. The same dose of oestradiol benzoate had no effect on uterine sensitivity to salbutamol. Previous studies have shown that this dose of oestradiol benzoate produces a twofold increase in uterine sensitivity to relaxin as an inhibitor of spontaneous contractions. Oestradiol influenced the ability of relaxin to inhibit oxytocin-stimulated uterine contractions. In corn oil-treated rats, uterine responses to relaxin were markedly reduced during oxytocin infusion compared with responses to relaxin before oxytocin; the maximum obtainable response to relaxin was less than 50% inhibition. In oestradiol-treated rats, uterine sensitivity to relaxin during oxytocin infusion was similar to that observed against spontaneous contractions. Cromakalim was able to inhibit uterine contractions during oxytocin infusion in both corn oil- and oestradiol-treated rats, uterine sensitivity to cromakalim being similar in the absence and presence of oxytocin for both hormone treatment groups. Salbutamol was also able to inhibit uterine contractions during oxytocin infusion in both corn oil- and oestradiol-treated rats. Oestradiol treatment increased the potency of salbutamol as an inhibitor of oxytocin-stimulated uterine contractions compared with corn oil treatment by 3·5-fold. The interaction of oestradiol and relaxin during late pregnancy may be important for attenuation of the myometrial response to stimulants. Journal of Endocrinology (1992) 135, 29–36

The influence of oestrogen and progesterone on the actions of two calcium entry blockers in the rat uterus

1988 ◽  
Vol 118 (2) ◽  
pp. 251-258 ◽  
Author(s):  
S. J. Downing ◽  
M. Hollingsworth ◽  
M. Miller
Keyword(s):  
Corn Oil ◽  
Late Pregnancy ◽  
Calcium Entry ◽  
Maximum Effect ◽  
Calcium Entry Blockers ◽  
Pregnant Rats ◽  
Ovarian Steroids ◽  
Uterine Contractions ◽  
Maximum Inhibition

ABSTRACT The potency and maximum effect of the calcium entry blocker nifedipine as an inhibitor of uterine contractions in vivo are increased in rats in late pregnant compared with non-pregnant rats. The influence of ovarian steroids produced during pregnancy (oestrogen and progesterone) on the potency and maximum effect of two calcium entry blockers (nifedipine and diltiazem) against uterine contractions during i.v. infusion was therefore investigated in anaesthetized non-pregnant rats. The influence of pregnancy on the relationship between serum concentrations of diltiazem during i.v. infusion and uterine and cardiovascular effects was also investigated. A twofold increase in the potency of nifedipine as an inhibitor of uterine contractions was observed in rats treated with oestrogen or oestrogen plus progesterone compared with rats treated with corn oil. There was no change in potency in rats receiving progesterone alone. Maximum inhibition of uterine contractions by nifedipine was significantly increased by all three hormone treatments. A twofold increase in the potency of diltiazem and a significant increase in maximum inhibition of uterine contractions was observed in rats in late pregnancy compared with non-pregnant rats. No increase in potency of diltiazem in reducing blood pressure or heart rate was observed in rats in late pregnancy. No significant difference in potency of diltiazem against uterine contractions was observed in rats treated with oestrogen, progesterone or oestrogen plus progesterone. In order to determine if the hormone-induced changes in the potency of nifedipine against contractions in vivo were due to a direct effect of the ovarian steroids on voltage-operated calcium channels of the uterus or were mediated by extra-uterine mechanisms, the potency of nifedipine as a relaxant of uterine spasms in vitro was investigated. The potency of nifedipine in the isolated uterus as a relaxant of the spasm induced by KC1 did not differ between rats which received oestrogen, progesterone or oestrogen plus progesterone or corn oil. Additionally, the potency of nifedipine to inhibit oxytocin-driven phasic tension development was not affected by treatment with oestradiol. These findings suggest that the increase in potency and maximum effect of nifedipine against uterine contractions observed previously in rats in late pregnancy can be ascribed, in part, to the action of the ovarian steroids (oestrogen and progesterone). The increase in potency of diltiazem observed in rats in late pregnancy, however, is due to factors other than oestrogen and progesterone. The lack of effect of hormonal manipulations on the potency of nifedipine on the isolated uterus suggests that the changes in potency in vivo due to oestrogen and progesterone are mediated by extra-uterine mechanisms. J. Endocr. (1988) 118, 251–258

Tocotrienol preserves ovarian function in cyclophosphamide therapy

2015 ◽  
Vol 34 (10) ◽  
pp. 946-952 ◽  
Author(s):  
HS Saleh ◽  
E Omar ◽  
GRA Froemming ◽  
RM Said
Keyword(s):  
Ovarian Function ◽  
Corn Oil ◽  
Concurrent Administration ◽  
Treatment Groups ◽  
Ovarian Protection ◽  
Normal Mean ◽  
Ovarian Size ◽  
And Function

Introduction: Cyclophosphamide (CPA) chemotherapy leads to ovarian failure and infertility. Tocotrienol (T3) is an antioxidant and anti-inflammatory agent. The role of T3 in ovarian protection throughout chemotherapy remains unclear. Aim: To investigate the role of T3 in the preservation of female fertility in CPA treatment. Method: Sixty female mice were divided into five treatment groups, namely, normal saline, corn oil only, T3 only, CPA and CPA + T3. The treatment was given for 30 days, followed by administration of gonadotrophin to induce ovulation. After killing, both ovaries were collected and examined histologically. Results: There was significant reduction in ovarian size in the CPA group compared with the normal group (CPA versus normal, mean area ± SD; 0.118 ± 0.018 vs. 0.423 ± 0.024 cm2; p ≤ 0.005), whilst concurrent administration of T3 with CPA leads to conservation of ovarian size (CPA + T3 vs. CPA, mean area ± SD; 0.285 ± 0.032 vs. 0.118 ± 0.018 cm2; p ≤ 0.005). Ovaries in CPA group showed abnormal folliculogenesis with accompanied reduced ovulation rate, follicular oedema, increased vascularity and inflammatory cell infiltration. These changes were reversed by concurrent T3 administration. Conclusion: Co-administration of T3 with CPA confers protection of ovarian morphology and function in vivo. These findings contribute to the further elucidation of CPA effect on ovary and suggest the potential of T3 use in preserving fertility in chemotherapy.

Influence of ovarian steroids on myometrial sensitivity and tolerance to relaxin in the rat in vivo: lack of cross-tolerance between relaxin, salbutamol and cromakalim

1992 ◽  
Vol 135 (1) ◽  
pp. 17-28 ◽  
Author(s):  
S. J. Downing ◽  
M. Hollingsworth
Keyword(s):  
Dependent Manner ◽  
Cross Tolerance ◽  
Pregnant Rats ◽  
Uterine Contractions ◽  
Adrenoceptor Agonist ◽  
Fold Reduction ◽  
Oestradiol Benzoate ◽  
Relaxin 2 ◽  
Dose Dependent

ABSTRACT The influence of oestradiol benzoate and progesterone on uterine sensitivity and development of tolerance to relaxin was investigated in bilaterally ovariectomized non-pregnant rats in vivo. Bolus doses of relaxin (2–20 μg/kg i.v.) produced rapid and reversible inhibition of uterine contractions in a dose-dependent manner. Treatment with oestradiol benzoate or oestradiol benzoate plus progesterone significantly increased uterine sensitivity to relaxin over 48 h by 2·4- to 8·5-fold. Tolerance to relaxin developed during continuous infusion of the hormone at 20 μg/kg per h for 40 h. A 7·8- to 17·4-fold reduction in sensitivity to relaxin was observed in relaxin-infused rats, whereas no change in sensitivity was observed in saline-infused rats. Infusion of relaxin at 50 μg/kg per h for 40 h produced a 131·8-fold reduction in uterine sensitivity to relaxin. The uterus remained tolerant to relaxin for up to 24 h after cessation of infusion. Treatment with oestradiol benzoate and/or progesterone did not influence the extent of tolerance development, but a more rapid recovery of uterine sensitivity to relaxin was observed in rats treated with oestradiol benzoate plus progesterone. Cross-tolerance with other uterine relaxant drugs was measured to investigate possible common mechanisms of action and sites of tolerance between relaxin and a β-adrenoceptor agonist (salbutamol) and potassium channel openers (cromakalim and minoxidil sulphate). No cross-tolerance was observed between relaxin and salbutamol, or relaxin and cromakalim or minoxidil sulphate. Cross-tolerance between cromakalim and minoxidil sulphate was seen. Journal of Endocrinology (1992) 135, 17–28

BEHAVIOURAL RESPONSES TO SEX STEROIDS OF GONADECTOMIZED AND SEXUALLY REGRESSED QUAIL

1976 ◽  
Vol 68 (1) ◽  
pp. 49-55 ◽  
Author(s):  
E. K. ADKINS ◽  
B. NOCK
Keyword(s):  
Testosterone Propionate ◽  
Hormone Treatment ◽  
Coturnix Japonica ◽  
Coturnix Coturnix Japonica ◽  
Equal Frequency ◽  
Treatment Groups ◽  
Coturnix Coturnix ◽  
Female Quail ◽  
Oestradiol Benzoate ◽  
Short Days

SUMMARY The purpose of these experiments was to compare the behavioural and morphological effects of exogenous sex hormones in gonadectomized quail (Coturnix coturnix japonica) with those in quail having regressed gonads as a result of exposure to short days. In Expt 1, male quail were assigned to one of three treatment groups: (1) intact, exposed to 16 h light:8 h darkness and injected with oil (group 16L); (2) gonadectomized, exposed to 16 h light:8 h darkness and injected with 2·5 mg testosterone propionate (TP)/day (group 16Lcastrated); and (3) intact, exposed to 8 h light:16 h darkness, and injected with 2·5 mg TP/day (group 8L). Groups 16L-castrated and 8L responded similarly to testosterone, copulating with equal frequency and rapidity after the same number of days of treatment, and also developing proctodeal (foam) glands of a similar size. Only on day 7 of testosterone treatment did the results for these two groups differ. By day 14, the behaviour of both groups resembled that of the 16L birds. In Expt 2 female quail were assigned to the same three treatment groups, except that the hormone treatment was 25 μg oestradiol benzoate/day. Group 8L became sexually receptive sooner than the 16L-ovariectomized quail, but by day 13 both groups had oviducts of similar size, were equally receptive, and were as receptive as the 16L females. The results suggest that the effects of photoperiod on sexual behaviour in this species are mediated largely, if not wholly, by the gonads. They also suggest that exposure to short days and surgical gonadectomy are rather similar experimental procedures in the quail.

Abstract MP11: Striatin Heterozygous Knockout Mice Have Increased Aldosterone Sensitivity

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Amanda E Garza ◽  
Luminita Pojoga ◽  
Rene Baudrand ◽  
Burhanuddin Moize ◽  
Tham Yao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Tissue ◽  
Rt Pcr ◽  
Kidney Weight ◽  
Treatment Groups ◽  
Primary Endpoints ◽  
Increased Sensitivity ◽  
First Time ◽  
Nongenomic Pathway

Background: We recently demonstrated that mice lacking one copy of the striatin gene (Strn+/-) have salt sensitivity of blood pressure (BP) as compared with WT mice. To determine whether Strn+/- mice have increased sensitivity to aldosterone (ALDO), we assessed the effect on blood pressure of an ALDO infusion in WT and Strn+/- mice fed a liberal sodium diet. Methods: In this study we used 12 week old WT and Strn+/- littermate male mice. For each genotype, mice were placed on HS diet and randomized to either: 1) placebo 2) ALDO (200 μg/Kg/day) or 3) ALDO plus 100 mg/kg/day eplerenone. BP was measured by tail cuff plethysmography at baseline and after treatment. After 21 days of treatment, animals were placed in metabolic cages for 24 hours. Finally, animals were sacrificed and organs excised. Primary endpoints were BP, renal immunohistochemistry, protein analysis by western blot and mRNA expression by RT-PCR. Results: BP increased significantly in Strn+/- mice treated with ALDO (ΔBP: 12 ± 4 mmHg, p=0.03) but not placebo (ΔBP 6± 6 mmHg); the BP effect of ALDO was blunted by eplerenone (Δ 6 ± 3 mmHg). In contrast, none of the treatments had a significant effect on BP in WT mice. Kidney weight was significantly increased after 3 weeks of ALDO treatment in both WT and Strn+/- mice and this increase in kidney weight was prevented by treatment with eplerenone, with no difference between genotypes. WT mice had an increase in glomerular volume (GV) in HS/ALDO treated that was blunted by eplerenone. Interestingly, Strn+/- mice had increased GV across all 3 treatment groups compared with WT mice. pAkt/Akt ratios were reduced in Strn+/- mice versus WT mice across all treatments. Classic genomic MR targets (ENaC and SGK1) and non-genomic targets (pAkt/Akt) were significantly modulated in kidney tissue of Strn+/- mice compared to WT mice with chronic ALDO. Conclusion: Strn+/- mice have an increased sensitivity to infused ALDO (increased BP response and increased rise in renal ENaC and SGK1 protein) as compared to WT mice. Since loss of striatin directly reduces nongenomic not genomic action of ALDO, this study demonstrates for the first time that modifying the nongenomic pathway may under chronic, in vivo conditions led to increased sensitivity to the genomic actions of ALDO.

Comparison of Grass Silage and Whole Crop Fodder Beet Silage When Fed to Ewes in Late Pregnancy

1993 ◽  
Vol 1993 ◽  
pp. 148-148
Author(s):  
J.V. O'Doherty ◽  
P.J. Quinn ◽  
T.F. Crosby
Keyword(s):  
Late Pregnancy ◽  
High Quality ◽  
Fodder Beet ◽  
Treatment Groups ◽  
Grass Silage ◽  
Long Term Experiments ◽  
Feeding Value ◽  
Cattle And Sheep

The use of fodder beet in rations fed to cattle and sheep has always been valued highly. Recent long-term experiments have shown that the palatability and high feeding value of fodder beet is fully preserved during the ensiling process.The objective of this experiment was to evaluate the performance of ewes in late pregnancy when fed either whole crop fodderbeet silage or grass silage.Mature (2-7 yrs), oestrous synchronised, twin bearing ewes (n=60) of mixed breeds (mainly Suffolk cross, greyface and halfbred), were selected following winter shearing and pregnancy scanning in December. At ten weeks prior to the predicted mean lambing date, the ewes were allocated to one of two treatment groups which were balanced for breed, age and liveweight. High quality precission chopped silage (DM 194 g/kg; CP 152 g/kg DM; in vivo ME 12.8 MJ/kg DM) and whole crop fodderbeet silage (WCFB)(DM 171 g/kg; CP126 g/kg DM; in vivo ME 11.7 MJ/kg DM) were fed in Tl and T2 respectively.

scholarly journals Respon Histopatologis Hepar Mencit (Mus musculus) yang Diinduksi Benzo(α)Piren terhadap Pemberian Taurin dan Ekstrak Daun Sirsak (Annona muricata)

2017 ◽  
Vol 16 (2) ◽  
pp. 54
Author(s):  
Annisa Agata ◽  
Endang Linirin Widiastuti ◽  
G. Nugroho Susanto ◽  
Sutyarso '
Keyword(s):  
Mus Musculus ◽  
Leaf Extract ◽  
Corn Oil ◽  
Annona Muricata ◽  
Group V ◽  
Group Iii ◽  
Treatment Groups ◽  
Randomized Design ◽  
Group I

Cancer is a disease that is characterized by the existence of damage and cell abnormality in growth and differentiation. Liver cancer is a disorder of hepar tissue derivated from its tumors. Taurine is known as antioxidant but its role as anticancer needs to be explored more as well the role of Annona muricata leaf extract which is believed to have its role as anticancer substance. This research, therefore, aimed to explore the effect of taurine and Annona muricata leaf extract on the hepar histopathology of male mice (Mus musculus) induced by benzo(α)pyren in vivo. This research was carried out by using a complete randomized design, which consisted of 5 treatment groups which was repeated 5 times. Group I was given 0.2 mL corn oil for 15 days, group II was induced by benzo(α)pyren without taurin nor A. Muricata leaf extract for 10 days, group III was given 7.8 mg taurine/BW/day (twice a day) starting from the 15 th days before the induction of benzo(α)pyren, group IV, after induced with benzo(α)pyren, taurine was given with dosage of 7.8 mg/BW/day, group V, after induced with benzo(α)pyren, soursop leaf extract was given with amount of 277.8 mg/BW/day. Data analyzed by Kruskal-Wallis test and one way ANOVA with Fisher test (p>0.05). The results indicated that taurine had ability to recover the liver tissue induced by benzo(α)pyren as (carcinogenic) while, Annona muricata leaf extract had not shown any recover of tissue damage

The depressing (negative) effect of oestradiol benzoate on the in vitro secretion of LH and FSH by the pituitary gland of the LRH-pretreated long-term ovariectomized rat changes into the augmentative (positive) effect after discontinuation of the LRH-pretreatment

1985 ◽  
Vol 110 (3) ◽  
pp. 329-337 ◽  
Author(s):  
G. A. Schuiling ◽  
H. Moes ◽  
T. R. Koiter
Keyword(s):  
Depressing Effect ◽  
Ovx Rats ◽  
Gonadotrophin Secretion ◽  
Oestradiol Benzoate ◽  
Negative Effect ◽  
Positive Effect ◽  
Perifusion System

Abstract. The effect of pretreatment in vivo with oestradiol benzoate on in vitro secretion of LH and FSH was studied in long-term ovariectomized (OVX) rats both at the end of a 5-day continuous in vivo pretreatment with LRH and 4-days after cessation of such LRH pretreatment. Rats were on day 0 sc implanted with osmotic minipumps which released LRH at the rate of 250 ng/h. Control rats were implanted with a piece of silicone elastomer with the dimensions of a minipump. On days 2 and 4 the rats were injected with either 3 μg EB or with oil. On day 5 part of the rats were decapitated and the in vitro autonomous (i.e. non-LRH-stimulated) and 'supra-maximally' LRHstimulated release of LH and FSH was studied using a perifusion system. From other rats the minipumps were removed on day 5 and perifusion was performed on day 9. On the 5th day of the in vivo LRH pretreatment the pituitary LH/FSH stores were partially depleted; the pituitaries of the EB-treated rats more so than those of the oil-injected rats. EB alone had no significant effect on the content of the pituitary LH- and FSH stores. On day 9, i.e. 4 days after removal of the minipumps, the pituitary LH and FSH contents had increased in both the oil- and the EB injected rats, but had not yet recovered to control values. In rats not subjected to the 5-days pretreatment with LRH EB had a positive effect on the supra-maximally LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. EB had no effect on the non-stimulated secretion of FSH. After 5 days of in vivo pretreatment with LRH only, the in vitro non-stimulated and supra-maximally LRH-stimulated secretion of both LH and FSH were strongly impaired, the effect correlating well with the LRH-induced depletion of the pituitary LH/FSH stores. In such LRH-pretreated rats EB had on day 5 a negative effect on the (already depressed) LRH-stimulated secretion of LH (not on that of FSH). EB had no effect on the non-stimulated LH/FSH secretion. It could be demonstrated that the negative effect of the combined LRH/EB pretreatment was mainly due to the depressing effect of this treatment on the pituitary LH and FSH stores: the effect of oestradiol on the pituitary LRH-responsiveness (release as related to pituitary gonadotrophin content) remained positive. In LRH-pretreated rats, however, this positive effect of EB was smaller than in rats not pretreated with LRH. Four days after removal of the minipumps there was again a positive effect of EB on the LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. The positive effect of EB on the pituitary LRH-responsiveness was as strong as in rats which had not been exposed to exogenous LRH. The non-stimulated secretion of FSH was again not affected by EB. The results demonstrate that the effect of EB on the oestrogen-sensitive components of gonadotrophin secretion consists of two components: an effect on the pituitary LRH-responsiveness proper, and an effect on the pituitary LH/FSH stores. The magnitude of the effect of EB on the LRH-responsiveness is LRH dependent: it is very weak (almost zero) in LRH-pretreated rats, but strong in rats not exposed to LRH as well as in rats of which the LRH-pretreatment was stopped 4 days previously. Similarly, the effect of EB on the pituitary LH and FSH stores is LRH-dependent: in the absence of LRH, EB has no influence on the contents of these stores, but EB can potentiate the depleting effect of LRH on the LH/FSH-stores. Also this effect disappear after cessation of the LRH-pretreatment.

OESTROGEN-PROGESTERONE RELATIONSHIPS IN THE INDUCTION OF OESTRUS IN SPAYED HEIFERS

1969 ◽  
Vol 45 (1) ◽  
pp. 99-109 ◽  
Author(s):  
M. J. CARRICK ◽  
J. N. SHELTON
Keyword(s):  
Behavioural Response ◽  
Normal Response ◽  
Oestradiol Benzoate ◽  
Small Doses ◽  
Refractory State ◽  
Increased Sensitivity ◽  
Repeated Doses ◽  
Effective Doses ◽  
Response Line ◽  
Normal Sensitivity

SUMMARY Experiments were conducted to examine the behavioural response of spayed heifers to oestrogen, and its modification by progesterone. In two groups of heifers, the median effective doses (MED) of oestradiol benzoate (ODB) were 121 and 132 μg. Repeated doses of ODB at physiological levels did not induce a state of refractoriness; in this respect the heifer is dissimilar to the ewe. However, repeated doses of 10 mg. ODB induced refractoriness to 400 μg. ODB. When such refractory heifers were treated with 10 mg. progesterone/day for 5 days, they showed a normal response to 400 μg. ODB given 3 days later. This return to normal sensitivity was not sustained, and pretreatment with progesterone was necessary for a normal response to subsequent small doses of ODB. The transient removal of the refractory state appears not to be due to a simple synergistic effect of residual progesterone, but to an effect of preconditioning a neural centre to respond to oestrogen. Increasing the duration of pretreatment with progesterone beyond 5 days did not result in a greater sensitivity to ODB. Pretreatment with progesterone in heifers not made refractory to ODB did not result in an increased sensitivity to ODB. Moreover, up to 7 days after termination of the progesterone treatment, the response to ODB was reduced and the slope of the dose-response line was less steep than when ODB was injected alone. The reduction of the response was more pronounced with 40 mg. progesterone/day than with 10 mg. The possible significance of these results in intact animals is discussed.

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