Contractions In Rabbits Research Articles

Development and characterization of contraction-suppressed full-thickness skin wound model in rabbits

The wound healing process in rodents (rats and mice) and lagomorphs (rabbits) predominantly relies on wound contraction rather than re-epithelialization and granulation tissue formation. As a result, existing laboratory animal models for wound healing often fail to mimic human wound healing mechanisms accurately. This study introduces a standardized rabbit model with superior translational potential for skin wound healing research. Two full-thickness dermal wounds were created on the posterior dorsal surface of each rabbit using a standard 2 ×2 cm² template. One of these wounds was randomly selected to be treated as a contraction-suppressed wound by applying a transparent adhesive elastic bandage. At the same time, the other was retained as a standard full-thickness wound. Wound contraction was measured on 7, 14, 21, 28, and 35 days. Histomorphological evaluation was done on day 35 to evaluate the quality of wound healing. The findings indicate that transparent adhesive elastic bandage prolonged the wound healing time and suppressed wound contraction in rabbits. In addition, the healed contraction-suppressed full-thickness wounds had denser and thicker collagen fibers than the healed standard full-thickness wounds, indicating better collagen fiber deposition. Our model achieved a 100 % success rate in maintaining the transparent adhesive elastic bandage in the rabbits. Therefore, we have developed a simple, non-invasive, cost-effective method for preventing wound contraction. Further studies are required to establish the utility of this model for studying wound healing mechanisms and evaluating therapeutic interventions.

Time-dependent Expression of Caspase-3 and Degeneration of Lateral Rectus Muscle on Experimental Esotropia in Rabbits

Background: To identify correlation between caspase-3 expression and degeneration of lateral rectus muscleon experimental esotropia in rabbits by using time dependent analysis. Methods: Twenty four rabbits weredivided into 4 groups, first month sham (S1); second month sham (S2); first month esotropia (E1); andsecond month esotropia (E2) model groups. Immunohistochemical and haematoxyllin eosin staining wereperformed. Results: In first month observation no significant difference in caspase-3 expression between S1(1.56 ± 1.03) and E1 (3.93 ± 1.66) groups (p >0.05) and in the degeneration score of lateral rectus musclebetween S1 (1.33 ± 1.36) and E1 (3.83 ± 2.04) groups (p> 0.05). In second month observation no significantdifference in caspase-3 expression between S2 (1.80 ±1.08) and E2 (6.50 ± 3.26) groups (p >0.05); butthere was significant difference in the degeneration score of lateral rectus muscle between S2 (1.16 ± 1.16)and E2 (4.50 ± 1.04) groups (p <0.05). There was a significant correlation between caspase-3 expressionand the degeneration score of lateral rectus muscle (p=0.020; r=0.471). Conclusion: On the experimentalesotropia with prolonged lateral muscle contraction in rabbits, the increasing trend of caspase-3 expressionhas a correlation with the increasing degeneration score of lateral rectus muscle.

Spatiotemporal Mapping of the Contracting Gravid Uterus of the Rabbit Shows Contrary Changes With Increasing Gestation and Dosage With Oxytocin.

Spontaneous and oxytocin induced contractile activity was quantified in the bicornuate uteri of pregnant rabbits maintained in situ, using data from two- and uni- dimensional video spatiotemporal maps (VSTM) of linear and area strain rate and compared statistically. Spontaneous contractions occurred over a range of frequencies between 0.1 and 10 cpm, in gravid animals at 18–21 and at 28 days of gestation, and propagated both radially and longitudinally over the uterine wall overlying each fetus. Patches of contractions were randomly distributed over the entire surface of the cornua and were pleomorphic in shape. No spatial coordination was evident between longitudinal and circular muscle layers nor temporal coordination that could indicate the activity of a localized pacemaker. The density and duration of contractions decreased, and their frequency increased with the length of gestation in the non-laboring uterus. Increasing intravenous doses of oxytocin had no effect on the mean frequencies, or the mean durations of contractions in rabbits of 18–21 days gestation, but caused frequencies to decrease and durations to increase in rabbits of 28 days gestation, from greater spatial and temporal clustering of individual contractions. This was accompanied by an increase in the distance of propagation, the mean size of the patches of contraction, the area of the largest patch of contraction and the overall density of patches. Together these results suggest that progressive smooth muscle hypertrophy and displacement with increasing gestation is accompanied by a decrease in smooth muscle connectivity causing an increase in wall compliance and that oxytocin restores connectivity and decreases compliance, promoting volumetric expulsion rather than direct propulsion of the fetus by peristalsis. The latter effects were reversed by the β2 adrenergic receptor agonist salbutamol thus reducing area of contraction, and the duration and distance of propagation.

Effects of ripasudil hydrochloride hydrate (K-115), a Rho-kinase inhibitor, on ocular blood flow and ciliary artery smooth muscle contraction in rabbits

Ripasudil, a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, is a novel drug for glaucoma in Japan. ROCK inhibition not only reduces intraocular pressure (IOP) but also increases ocular blood flow. We investigated the effects of ripasudil on optic disc blood flow (ODBF) in rabbit eyes and in isolated rabbit ciliary arteries. We measured IOP by tonometry and ODBF by laser speckle flowgraphy (LSFG) in male Dutch rabbits. A single drop (20μL) of 0.8% ripasudil was delivered to the ocular surface after topical application of phenylephrine hydrochloride to reduce the ODBF. The effects of ripasudil on isolated rabbit ciliary artery smooth muscle contractions were measured in vitro with a myograph. Ripasudil inhibited the reduction of ODBF induced by phenylephrine at 30 and 120min after instillation (P<.05). The blood flow change was not significantly correlated with the IOP change. Ripasudil induced a concentration-dependent relaxation in isolated rabbit ciliary arteries precontracted with a high-potassium solution. This relaxation was not mediated through the endothelium-dependent activities of nitric oxide synthase, prostacyclin, or the large-conductance calcium-activated K+ channel as shown by the inability of specific inhibitors of these pathways to block the ripasudil-induced relaxation. Taken together, our results showed that ripasudil not only decreased IOP but also increased ODBF in rabbits. However, the changes in IOP were not correlated with the changes in ODBF. Ripasudil also induced a concentration-dependent relaxation of isolated rabbit ciliary arteries through a NO-independent mechanism. Further investigation of the effect of ripasudil on ODBF is needed.

Spasmogenic and spasmolytic activity of rind of Punica granatum Linn

BackgroundRind of Punica granatum is traditionally used in treatment of abdominal cramps and various GIT disorders. So far spasmolytic activity of rind of Punica granatum has been reported using in vitro model. However, its mode of action is not explored yet. Therefore, the current work describes the possible mode of action for spasmolytic activity of methanolic extract of rind of Punica granatum (Pg. Cr). Acute toxicity study is also performed to determine its safe dose range.MethodsRind of Punica granatum was subjected to shade drying. Shade dried materials were pulverized using conventional grinder. Grinded materials were macerated in commercial grade methanol. The extract of rind of P. granatum was concentrated using a rotary evaporator. Rabbits’ jejunal preparations were mounted in organ bath containing 10 ml Tyrode’s solution, constantly aerated with carbogen gas. Pg. Cr was tested on spontaneous rabbits’ jejunal preparations in concentrations 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml. Pg. Cr was also tested on KCl (80 mM)-induced contractions in rabbits’ jejunal preparations. Since we observed spasmogenic activity for the first time, hence we also determined the effects of Pg. Cr in presence of atropine (0.03 μM). Pg. Cr was also tested in presence of 0.03 μM of loratadine HCl. Pg. Cr was also tested on barium chloride induced contractions. Calcium Concentration Response Curves (CCRCs) were constructed in the absence and presence of test samples of Pg. Cr in decalcified tissues to explore its possible mode of action. Acute toxicity screening was also performed to determine its safe dose range.ResultsPhytochemical screening revealed the presence of saponins, tannins, carbohydrates, proteins, flavonoids, saponins and steroids. However, Pg. Cr tested negative for alkaloids and triterpenoids. Pg. Cr was safe up to 100 mg/kg with its LD50 = 1305 mg/kg. Its respective EC50, in the absence and presence of atropine, were 9.7 ± 0.3 and 3.12 ± 0.45 mg/ml. In the presence of 0.02 and 0.08 μM of loratadine HCl, respective EC50 were 5.6 ± 0.4 and 2.8 ± 0.15 mg/ml. EC50 for relaxant effects on KCl-induced contractions was 8.6 ± 1 mg/ml. In the presence of 0.3 mg/ml of Pg. Cr, a right shift was observed with EC50 (log [Ca++]M) = -1.8 ± 0.09 vs. control EC50 -2.6 ± 0.01. Similarly, EC50 for verapamil (0.1 μM) was −2.4 ± 0.011vs. control EC50= -2.4 ± 0.01. The right shift of P. granatum resembled the right shift of verapamil suggesting for inhibition of voltage gated calcium channels.ConclusionsP. granatum is safe up to 100 mg/kg. In low concentrations, P. granatum produced spasmogenic activity possibly through involvement of cholinergic and histaminergic receptors. The spasmolytic action may follow inhibition of the voltage gated calcium channels.

Experimental evaluation of effects of a pyrimidine derivative 4CPTP on cardiovascular system

Aim: To study the effects of pyrimidine derivative 4CPTP on cardiovascular system. Material and methods: Ionotropic and chronotropic effects of 4CPTP were studied using rabbit heart and frogs heart in situ preparation. Dogs blood pressure preparation was used to assess the effects of 4CPTP on blood pressure. Results: The test compound, like phenobarbitone produced dose dependent decrease in heart rate and amplitude of contractions of rabbit and frog heart and decrease in blood pressure in dogs. Conclusions: 4 CPTP possesses negative ionotropic and negative chronotropic action along with hypotensive action in animal models.

Vascular Reactivity of Rat, Guinea‐pig, Rabbit and Human Vessels to Bufadienolides and Cardenolides

Cardenolides and bufodienolides are Na+-K+-ATPase (NKA) inhibitors. The aim of the present study was to evaluate the response to such compounds of vessels from different species in order to compare potency and efficacy. The experimental protocols were approved by the Animal Care and Ethics Committee of the Ceara State University. The aortic rings and mesenteric artery for isometric recordings of contractions in response to cumulative addition of OUA, BUF, DIG (0.1-100 µM). The contractions were expressed as percentage of the maximal contraction elicited by phenylephrine. Ouabain, up to 100 µM, promoted no contraction in rat aorta but promoted a slow onset contraction that attained a maximum of 71.5±14.8% and 101.2±8.5% in guinea-pig and rabbit tissue, respectively. Bufalin promoted slow onset contractions after 30 and 100 µM that reached a maximum of 20.6 ± 5.2%,55.0±10.5% and 94±19.8% in tissues gathered from rats, guinea-pigs and rabbits, respectively. On the other hand, digoxin did not elicit contraction in rabbit or rat aortic rings but elicited a similar slow onset that attained its maximum after more than 50 minutes and reached 79.7±15.6% in guinea-pig tissues. In human aortic rings in response to 100 µM bufalin or ouabain reached a maximum of 96.7±24.4% or 140±26.7%, respectively. In the 2nd branch of the mesenteric artery, BUF promoted a slow contractile response (46 % ± 9.6 %) only at a dose of 100 µM.Pretreatment with guanethidine (GUA + BUF) significantly attenuated BUF vasoconstriction in aortic rings (39.7% ± 8.4) and prazosin (1µM) completely blocked the contraction, suggesting and indirect noradrenergic activation.

Allometric scaling relationship between frequency of intestinal contraction and body size in rodents and rabbits

This study aimed to establish an allometric scaling relationship between the frequency of intestinal contractions and body mass of different mammalian species. The frequency of intestinal contractions of rabbit, guinea pig, rat and mouse were measured using an isolated organ system. The isolated rings were prepared from proximal segments of jejunums and the frequency of contractions was recorded by an isometric force procedure. The coefficients of the obtained allometric equation were ascertained by computation of least squares after logarithmic transformation of both body mass and frequency. Significant differences (p less than 0.001) were shown in the frequency of contractions between different species. The highest frequency that corresponded to the mice was 57.7 min-1 and the 95 percent confidence interval (CI) ranged from 45.4 to 70, while rabbits showed the lowest frequency (12.71 min-1, CI: 8.6-16.8). Logarithms of frequency were statistically proportional to logarithms of body mass (r00.99; p less than 0.001). The data fitted an equation F 1/4 18:51B 0:31 and the 95 percent confidence interval of the exponent ranged from -0.30 to -0.32. The results of this study suggest that it is probably possible to extrapolate the intestinal contraction frequency of other mammalian species by the means of allometry scaling.

Altered expression of connexin43 and its possible role in endothelin - 1 - induced contraction in rabbit basilar artery

Objective To investigate the role of connexin43 in ET- 1 -induced contraction in rabbit basilar artery.Methods The ET - 1 - induced contraction without or with carbenoxolone was studied with an isometric tension system.The expression of connexin43 protein in ET - t stimulated basilar arteries was studied with Western blot.Scrape/scratch method was used to analyze the function of gap junction in cultured rabbit cerebrovascular smooth muscle ceils.Results ET - 1 produced a concentration - dependent contraction.Carbenoxolone inhibited ET- 1 induced contraction.The connexin43 protein level was increased in ET- 1stimulated basilar arteries.Carbenoxolone decreased the connexin43 protein level increased by ET - 1.Cells treated with ET - 1 appeared positive communication and the dye transfer was increased in a time - dependent fashion.Carbenoxolone suppressed the ET - 1 - induced increasement of dye transfer.Conclusions The enhancement of gap junction intercellular communication is activated by ET - 1 via modulating the expression of connexin43,and plays an important role in the pathogenesis of cerebral vasospasm.Inhibition of vascular GJIC as a means of reducing cerebral vasospasm after SAH may have therapeutic advantage. Key words: Connexin43 ; Gap junction ; ET - 1 ; Cerebral vasospasm

Effect of acute cold exposure on lung perfusion and tracheal smooth muscle contraction in rabbit

Acute exposure to cold temperature can affect the respiratory system of those exposed to extreme weather and induces asthma in asthmatic patients. However, the effect on lung perfusion and the pulmonary circulation was not addressed in any previous study. The present study investigates the effects of acute cold exposure on tracheal smooth muscle and lung perfusion. New Zealand White rabbits were used in these experiments. For in vitro experiments, isolated tracheal segments were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissue response to cooling from 37 to 4°C was examined. For in vivo experiments, the rabbits were kept in a cold room (4°C) for 1h. Lung perfusion scintigraphy was performed at the end of this period. Each rabbit was injected with 74MBq (2mCi) technetium-99m macroaggregated ((99m)Tc MAA). Perfusion studies were done by using Gamma camera equipped with a low-energy, high-resolution, parallel-hole collimator interfaced with a computer. Static images were acquired 5min after administration of the radiotracer. Cooling induced a rapid and reproducible contraction in the tracheal smooth muscle. Rabbits exposed to cold temperature had lesser lung perfusion than controls using radionuclide perfusion study. Our results highlight the response of tracheal muscle and pulmonary circulation to cold exposure. These results indicate that cooling induced contraction of the trachea and decreased pulmonary circulation and lung perfusion. This summation of acute cooling for tracheal smooth muscle and pulmonary circulation seems to be the reason for the severe cooling-induced contraction.

Role of Rho‐kinase in contractions of ureters from rabbits with unilateral ureteric obstruction

To investigate the expression of two isoforms of Rho-kinase (ROCK) and its functional role in the pathophysiological control of smooth muscle contraction in rabbits with unilateral ureteric obstruction (UUO). Left UUO was created in 14 rabbits and eight other rabbits (controls) had sham operations. After 2 weeks all the rabbits were killed. Ureteric strips suspended in an organ bath were used for functional studies and the effects of Y-27632, a specific inhibitor of Rho-kinase, on spontaneous contractions and electrical field stimulation (EFS; 50 V, 1 ms, 16 Hz, for 20 s), carbachol- (10(-7)-10(-4)m), phenylephrine- (10(-7)-10(-4)m) and KCl- (50 mm) induced contractions were analysed. Western blotting was used to determine expression levels of Rho-kinase protein in the ureters of UUO and control rabbits. In the functional analysis, the contractions induced by EFS, KCl, phenylephrine and carbachol in the ureteric strips from rabbits with UUO were significantly greater than those from the control rabbits. Y-27632 considerably suppressed the ureter contractile responses in both UUO and control rabbits. Western blot analysis showed that both ROCK-1 and ROCK-2 proteins were expressed in the rabbit ureter. In accordance with the functional studies, the expression levels of both ROCK-1 and ROCK-2 were significantly greater in the ureters of UUO rabbits than in the controls. Y-27632 suppressed ureteric contractions in the rabbits with UUO. Western blot analysis also confirmed greater expression levels of ROCK-1 and ROCK-2 in the ureters of UUO rabbits. It is important to elucidate by which mechanisms the Rho-kinase pathway affects ureteric function after obstruction.

Involvement of phospholipase C in endothelin 1–induced stimulation of Ca++ channels and basilar artery contraction in rabbits

Endothelin 1 (ET-1) is a major cause of cerebral vasospasm after subarachnoid hemorrhage (SAH), and extracellular Cal++ influx plays an essential role in ET-1-induced vasospasm. The authors recently demonstrated that ET-1 activates two types of Ca"-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Cal++ channel (SOCC) in vascular smooth-muscle cells located in the basilar arteries (BAs) of rabbits. In the present study, they investigate the effects of phospholipase C (PLC) on ET-1-induced activation of these Ca++ channels and BA contraction by using the PLC inhibitor U73122. Methods. To determine which Cal++ channels are activated via a PLC-dependent pathway, these investigators monitored the intracellular free Cal++ concentration ([Ca++]i). The role of PLC in ET-1-induced vascular contraction was examined by performing a tension study of rabbit BA rings. The U73122 inhibited the ET-1-induced transient increase in [Ca++]i, which resulted from mobilization of Ca++ from the intracellular store. Phospholipase C also inhibited ET-1-induced extracellular Ca++ influx through the SOCC and NSCC-2, but not through the NSCC-1. The U73122 inhibited the ET-1-induced contraction of the rabbit BA rings, which depended on extracellular Cal++ influx through the SOCC and NSCC-2. Conclusions. These results indicate the following. (1) The SOCC and NSCC-2 are stimulated by ET-1 via a PLC-dependent cascade whereas NSCC-1 is stimulated via a PLC-independent cascade. (2) The PLC is involved in the ET-1-induced contraction of rabbit BA rings, which depends on extracellular Ca++ influx through the SOCC and NSCC-2.

Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery

The influence of alloxan-induced diabetes on the reactivity of rabbit basilar artery to endothelin-1 was examined. Endothelin-1 induced concentration-dependent contraction of basilar arteries that was higher in diabetic than in control rabbits. Endothelium removal produced a higher enhancement of the endothelin-1-induced contraction in control than in diabetic rabbits. N G-nitro- l-arginine ( l-NOArg) enhanced the maximal contraction induced by endothelin-1 in control rabbits and potentiated this response in diabetic rabbits. Endothelin ET A receptor antagonist, cyclo( d-Asp-Pro- d-Val-Leu- d-Trp) (BQ-123), inhibited endothelin-1-induced contraction in both rabbit groups. Endothelin ET B receptor antagonist, 2,6-Dimethylpiperidinecarbonyl-γ-Methyl-Leu-N in-(Methoxycarbonyl)- d-Trp- d-Nle (BQ-788), enhanced endothelin-1-induced contraction in control rabbits and decreased the potency of endothelin-1 in diabetic rabbits. Sodium nitroprusside-induced relaxation of basilar arteries was lower in diabetic than in control rabbits. These results suggest that mechanisms underlying rabbit basilar artery hyperreactivity to endothelin-1 include decreased endothelial modulation of endothelin-1-induced contraction, with impaired endothelial endothelin ET B receptor activity; decreased sensitivity to nitric oxide (NO) in vascular smooth muscle; and enhanced participation of muscular endothelin ET A and ET B receptors.

Evidence that the hypotensive effect of WAY 100635, a 5-HT1A receptor antagonist, is related to vascular alpha 1-adrenoceptor blockade in the adult rat.

1. The effect of WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride), a 5-HT1A receptor antagonist, on cardiovascular function was studied. 2. The i.v. injection of WAY100635 dose-dependently decreased blood pressure in anaesthetized rats; while in pithed rats WAY100635 (1 mg kg(-1)) displaced the phenylephrine pressor effect. 3. WAY100635 antagonized phenylephrine-induced contraction in rabbit and rat aorta (pA2 of 6.88 and 7.93 and Schild slopes of -0.83 and -1.21, respectively); while in rat caudal artery pK(B) was 7.45 and the Schild slope of -0.56, suggesting a complex interaction in this vessel. 4. The results show that WAY100635 induced hypotension in the anaesthetized rat and suggest that this effect could be partially explained by antagonism of vascular alpha1-adrenoceptors.

Regulation of proximal tubule sodium/hydrogen antiporter with chronic volume contraction.

We developed a model of volume contraction in rabbits by using a furosemide/low-salt diet to follow changes, if any, in proximal tubule Na+/H+ exchanger 3 (NHE3) mRNA and brush-border protein. The rabbits' plasma renin, aldosterone, and urine sodium content confirmed the volume-contracted state. RNase protection assays demonstrated increases in treated-animal NHE3 mRNA as a percentage of control with 172 +/- 23, 154 +/- 15, 153 +/- 14, and 141 +/- 7 (SE) % (P < 0.05) at 1, 5, 10, and 31 days, respectively. Western analysis of brush-border membrane with NHE3 antibody revealed increased immunoreactivity in treated animals as a percentage of control with 120 +/- 30, 190 +/- 59, 307 +/- 72, and 427 +/- 41% (P < 0.05) at 1, 5, 10, and 31 days, respectively. There was no significant difference in serum potassium, bicarbonate, and cortisol in control vs. experimental animals. These data suggest that there is chronic upregulation of NHE3 in the volume-contracted state.

Effects of Neostigmine on Tracheal Smooth Muscle Contraction in Rabbits

Effects of Neostigmine on Tracheal Smooth Muscle Contraction in Rabbits

Group III muscle afferents evoke reflex depressor responses to repetitive muscle contractions in rabbits.

Repetitive-twitch contraction of the hindlimb muscles in anesthetized rabbits consistently evokes a reflex depressor response, whereas this type of contraction in anesthetized cats evokes a reflex pressor response in about one-half of the preparations tested. Rapidly conducting group III fibers appear to comprise the afferent arm of the reflex arc, evoking the depressor response to twitch contraction in rabbits because electrical stimulation of their axons reflexly decreases arterial pressure. In contrast, electrical stimulation of the axons of slowly conducting group III and group IV afferents reflexly increases arterial pressure in rabbits. In the present study, we examined the discharge properties of group III and IV muscle afferents and found that the former (i.e., 13 of 20), but not the latter (i.e., 0 of 10), were stimulated by 5 min of repetitive-twitch contraction (1 Hz) of the rabbit triceps surae muscles. Moreover, most of the group III afferents responding to contraction appeared to be mechanically sensitive, discharging in synchrony with the muscle twitch. On average, rapidly conducting group III afferents responded for the 5-min duration of 1-Hz repetitive-twitch contraction, whereas slowly conducting group III afferents responded only for the first 2 min of contraction. We conclude that rapidly conducting group III afferents, which are mechanically sensitive, are primarily responsible for evoking the reflex depressor response to repetitive-twitch contractions in anesthetized rabbits.

Interleukin-8 potentiates the effect of interleukin-1-induced uterine contractions.

The aim of this research was to study the effect of exogenous interleukin (IL)-8, IL-1 and IL-8 + IL-1 on uterine contractions in rabbits. Four equal groups of non-pregnant rabbits (n = 24) were investigated using either placebo or experimental drugs in the form of vaginal suppositories. The suppositories contained human recombinant IL-8 (200 ng), IL-1 (200 ng), IL-8 (200 ng) + IL-1 (200 ng) or vehicle Witepsol base, 500 microliters). Subsequently, the plasma concentration of prostaglandin (PG) E2 was estimated 3 h after the last dose of treatment. Neutrophil infiltration in the endometrial tissue was studied with anti-rabbit RT2 staining. Suppositories with IL-1 and IL-8 + IL-1 produced contractile responses with increased frequency (P < 0.003, P < 0.0005) and amplitude (P < 0.0001) in vivo, compared with vehicle. IL-1 and IL-8 + IL-1 also caused similar contractile effects with increased frequency (P < 0.01, P < 0.0007) and amplitude (P < 0.0001) in an in-vitro experiment than vehicle. The frequency and amplitude of uterine contractions were more significant with IL-8 + IL-1 than that of IL-1, both in vivo (P < 0.002, P < 0.05) and in vitro (P < 0.005, P < 0.01). IL-8 did not induce any contractions. Prostaglandin concentration was increased approximately 8-fold with IL-8 + IL-1 (P < 0.0001) and 2.5-fold with IL-1 treatment (P < 0.0001). Neutrophil numbers were significantly increased with IL-8 + IL-1 > IL-8 > IL-1 (P < 0.002, P < 0.0003 and P < 0.008) compared with vehicle. Our data suggest that IL-8 stimulates IL-1-induced uterine contractions through PGE2 production and could be an important process during labour and delivery.

Ability of intrauterine bacterial lipopolysaccharide to cause in situ uterine contractions in pregnant rabbits

To investigate the ability of bacterial lipopolysaccharide delivered by the intra-uterine route to cause uterine contractions in rabbits, and to assess the suppressive effect of urinary trypsin inhibitor on them. Both pregnant and non-pregnant rabbits were chronically implanted with a force-transducer to make it possible to record isometric uterine contractions under unanesthetized and unrestrained conditions. Lipopolysaccharide (10 micrograms/animal) was administered via a catheter to their uteri; and then, after confirmation of lipopolysaccharide-induced uterine contractions, urinary trypsin inhibitor (3,000 or 10,000 units/animal/time) or saline solution was injected through the catheter, 5 times for pregnant animals or 3 times for non-pregnant animals at 1-hour intervals in both cases. Their uterine contractions were continuously recorded for 3 to 5 hours. Effects of lipopolysaccharide (10 micrograms/ml) and urinary trypsin inhibitor (100 and 1,000 units/ml) on the contraction of isolated uteri from pregnant mice were also measured, as was their production of prostaglandin E2 and prostaglandin F2 alpha by an enzyme immunoassay method. Lipopolysaccharide augmented the in situ uterine contractions in both pregnant and non-pregnant rabbits, as well as the in vitro contractions of isolated uteri from pregnant mice. Lipopolysaccharide also increased the uterine prostaglandin production. Urinary trypsin inhibitor inhibited significantly the lipopolysaccharide-induced uterine contractions and the prostaglandin production. Lipopolysaccharide enhanced uterine contractions through, at least partly, a direct mechanism via uterine prostaglandin production, which action could explain the onset of preterm delivery due to intrauterine bacterial infection. As urinary trypsin inhibitor suppressed the lipopolysaccharide-induced uterine contractions, this inhibitor may be a hopeful candidate of a drug for prevention of preterm delivery.

Effect of skeletal muscle fiber type on the pressor response evoked by static contraction in rabbits

The purpose of this study was to determine whether the reflex hemodynamic responses to static contraction of predominately glycolytic muscle are greater than the changes elicited by primarily oxidative muscle. Low-frequency electrical stimulation (continuous 21 days) of the tibial nerve of one hindlimb of adult rabbits converted the metabolic characteristics of the predominately glycolytic gastrocnemius to a muscle that was primarily oxidative. After 21 days of stimulation, the rabbits were decerebrated, and static contraction of the glycolytic muscle (unstimulated gastrocnemius) initially decreased heart rate (HR; -16 +/- 3 beats/min) and mean arterial pressure (MAP; -17 +/- 3 mmHg). Thereafter, MAP increased 13 +/- 3 mmHg above baseline. Static contraction of the oxidative muscle (stimulated gastrocnemius) produced similar decreases in HR and MAP (-12 +/- 4 beats/min and -12 +/- 3 mmHg, respectively). However, the subsequent increase in MAP (8 +/- 3 mmHg; above baseline) was less than that evoked by contraction of the glycolytic muscle. The responses evoked by stretch of each muscle and high-intensity electrical stimulation were the same, indicating that the afferents from the muscle were not destroyed by the chronic-stimulation technique. These results support the hypothesis that metabolic by-products play a role in the pressor response to static contraction of skeletal muscle. In addition, these data confirm that contraction of predominately oxidative muscle can evoke a reflex pressor response, albeit smaller than the change elicited from primarily glycolytic muscle.