Effect of chloroquine on strips of non-pregnant and pregnant mice uteri in-vitro.

Chloroquine (CQ) remains the household drug for the treatment of malaria especially among pregnant women. However, there are reports that CQ inhibits the contractile process in non-pregnant rat's uterus. The aim of this study is to compare responses to CQ between non-pregnant and pregnant mice and identify some mechanisms involved. Experiments were carried out in non-pregnant and pregnant mice pretreated 24 hours before with 1.5 mg/kg-body weight stilboesterol given orally. Strips of uterine smooth muscle, approximately 5 mm in diameter, were mounted in a 20 ml organ bath containing De Jalon solution bubbled with a 95% O2-5% CO2 gas mixture. Responses of the strips to graded concentration of acetylcholine (ACh) (10(-9) to 10(-5) mol/L), oxytocin (OXY) (10(-5) to 10(-2) IU/ml) and CQ (10(-6) to 4 x 10(-4) mol/L) were investigated. The strips were then incubated in 4 x 10(-4) mol/L CQ for 15 mins and the cumulative dose responses for OXY were repeated. To investigate mechanism of action, the strips were incubated for 15 mins in N(w)-nitro L-arginine methyl ester (L-NAME) and the cumulative responses to CQ repeated. Each investigation was carried out in fresh tissue mounted on Grass Model FT03 force transducer coupled unto a 4-channel Grass Model 7D Polygraph. CQ (low to moderate level), ACh and OXY led to increases in contractile responses in the uteri. There were greater contractile responses in non-pregnant than pregnant mice to CQ and ACh. At high doses, CQ had an inhibitory effect on the uterine contraction. Incubating in CQ led to abolition of contractile responses to OXY and ACh. In the presence of L-NAME, inhibitory effect of CQ at high doses was attenuated in pregnant mice only. The results suggest that CQ at high doses inhibits contractile responses in non-pregnant and pregnant mice. Enhanced nitric oxide bioactivity attenuated this inhibitory effect.

Contractile effect of the aqueous extract of Psidium guajava leaves on aortic rings in rat.

Aqueous leaves extract of Psidium guajava significantly and dose-dependently (0.25-2 mg/ml) contracted aorta rings. The effect was evaluated also in presence of nifedipine and phentolamine. The sensitivity of the aortic rings to cumulative doses of P. guajava was significantly enhanced in the presence of phentolamine suggesting that the effect of P. guajava was to a large extent mediated by activation of alpha-adrenoceptor and to a lesser extent by acting via calcium ion channel.

Morinda lucida reduces contractility of isolated uterine smooth muscle of pregnant and non-pregnant mice.

The present work investigated the effect of Morinda lucida (M. lucida) extract on isolated uterine smooth muscle of pregnant and non-pregnant mice. Pregnant and non-pregnant mice were pretreated with oral stilboesterol (0.1 mg/kg body weight) and killed by cervical dislocation. Thin strips of the uterus were cut and mounted in a 20 ml organ bath containing De Jalon solution bubbled with 95%O2-5% CO2 gas mixture. The strips were connected to a force transducer coupled to a Grass 7D Polygraph for the recording of isometric tension. Effects of graded concentrations of oxytocin (OXY; 10-5-10-2 mol/L), acetylcholine (ACh; 10-9-10-5 mol/L) and M. lucida extract (0.015-1.5 mg/ml) were recorded. Fresh uterine strips were then incubated with M. lucida extract for 5 mins and cumulative response to OXY was repeated. Another set of fresh strips was incubated in L-NAME for 15 mins and the cumulative responses to M.lucida extract were repeated. OXY resulted in increased contractile responses in both pregnant and non-pregnant uterine muscles. M. lucida resulted in relaxation of the uterine smooth muscle in both pregnant and non-pregnant mice at all doses. However, at 1.5mg/ml, M. lucida completely blocked spontaneous uterine contractions. Following incubation with L-NAME, M. lucida extract led to a slightly greater relaxation of the uterine strips. In conclusion, M. lucida reduced contractility of uterine smooth muscle in both pregnant and non-pregnant mice as well as blocking contractile responses to OXY and Ach in uterine smooth muscle of pregnant and non-pregnant mice. There was no significant alteration of M. lucida activity by L-NAME suggesting that the action of the compound on uterine muscle is not associated with impaired nitric oxide synthase.

Impaired baroreflex sensitivity and responses to angiotensin converting enzyme inhibitor in salt-induced hypertension and its prevention by dietary calcium supplement in Sprague-Dawley rats.

The role of renin-angiotensin system and baroreceptors in the pathogenesis and prevention of hypertension due to salt-loading and concurrent dietary calcium for 6 weeks in Sprague-Dawley rats were studied. Blood pressure measurements were done in anaesthetized animals while the activities of renin-angiotensin and parasympathetic nervous systems were determined by the effect of their inhibition on the arterial pressure and baroreflex sensitivity, via captopril infusion and vagotomy respectively. The sympathetic nervous system activity and its effect on baroreflex response were estimated by combined captopril infusion and vagotomy. There was elevation of mean arterial pressure (MAP) in salt-loaded rats (SR) relative to controls (NR) (140.5 +/- 2.18 vs 98.0 +/- 1.38 mmHg) without any significant effect on heart rate (HR) (406 +/- 8.58 vs 428 +/- 11.20 beats/min). Calcium supplement abolished the rise in MAP of salt-loaded-calcium-fed rats (SCaR) (102.8 +/- 2.30 mmHg) but led to reduction in their HR (389 +/- 10.21 beats/ min) relative to control. Renin-angiotensin system inhibition led to fall in MAP in all groups of rats with the greatest reduction observed in SR. Inhibition of parasympathetic effects resulted in elevation of MAP in all thegroups. with SCaR and CaR having the highest rise. SR and SCaR had higher sympathetic activity than NR and CaR. Bilateral carotid occlusion test showed decrease baroreflex sensitivity in SR compared with NR while those of SCaR were enhanced without significantly affecting CaR. Also, there was enhanced baroreflex response (BRR) due to renin-angiotensin system inhibition in NR and SR while it was significantly reduced in SCaR but none in CaR. However, there was reduced BRR to parasympathetic inhibition in experimental groups except in CaR. Unmodified sympathetic activity resulted in enhanced BRR in all the groups. The results of the present study suggests that renin-angiotensin and autonomic nervous systems are impaired by dietary salt-loading, while prevention of salt-hypertension by calcium supplement is through modulation of these actions.

Chronic ethanol consumption alters vascular smooth muscle responses in rats.

1. The effect of chronic ethanol (10%) consumption for 5 months on vascular smooth muscle (VSM) using aortic rings of both sexes of Sprague-Dawley rats was studied. 2. Chronic ethanol consumption increased the sensitivity of VSM to noradrenaline (NA) in both male and female ethanol-treated rats. 3. There was no significant difference in the contractile response of male and female ethanol-treated rats to NA. Hence, the enhancement of vascular contractility to the agonist due to chronic ethanol consumption is independent of gender. 4. Vascular relaxation induced by acetylcholine showed similar responses in all experimental groups. Thus, chronic ethanol consumption seems to have no significant effect on the production of endothelium-dependent relaxing factor. 5. However, the VSM sensitivity to potassium chloride was increased in female ethanol-treated rats, whereas male ethanol-treated rats had similar responses as controls. 6. The results suggest that the effect of chronic ethanol consumption on VSM varies with gender. Impairment of VSM in male ethanol-treated rats is due partly to changes in the receptor-operated channel, whereas in females it is due to changes in both receptor- and potential-operated channels.