Oxytocin, a posterior pituitary hormone, is also synthesized in the heart and blood vessels. This signifies its importance in cardiovascular regulation. Sexual dimorphism in cardiovascular responses to oxytocin has been reported in hypertensive animals. We intended to investigate the importance of lipid mediators like the platelet activating factor (PAF) in the cardiovascular responses to oxytocin in male and female rats. Animals were pretreated with platelet activating factor antagonists, WEB 2086 (20 mg/kg) or Ginkgo Biloba (60 mg/kg), and vascular and heart rate responses to oxytocin were ascertained. The results of this study show that pre-treatment with WEB 2086 or Ginkgo Biloba attenuated the vasoconstriction in hindquarters mediated by oxytocin in male and female rats, i.e. a decrease in flow rate from 40.31% (P < 0.01) to 15.58% and 11.41% in females, respectively, while the modification in males was much less, i.e. from 19.15 % (P<0.05) to 13.39% and 4.49%, respectively. In the other groups of animals utilized for estimation of heart rate, pre-treatment with WEB 2086 (20 mg/kg i.v.) or Ginkgo Biloba (60 mg/kg i.v.) elicited similar results, i.e. enhanced decrease by oxytocin in heart rate from control level in females, demonstrating that in female animals there was potentiated decrease of 18.67% (P < 0.01) and 12.74% (P < 0.05) in the heart rate from control value as compared to the male rats which displayed a mild increase in heart rate. This study suggests that inhibition of PAF unmasks sexually dimorphic cardiovascular responses to oxvtocin.
A prospective study based on WHO core indicators was undertaken in the Departments of Medicine, Surgery, Ophthalmology, Orthopaedics and Gynaecology to determine the prescribing practices at the Christian Medical College and Hospital, Ludhiana (India). It was conducted by interacting with 225 patients on their first and second visits to the outpatient department (OPD). It was observed that the average number of drugs prescribed was more on the second visit as compared to the first visit and only 25% of the drugs were prescribed by generic name. Two-thirds of the drugs were prescribed from the hospital formulary. Antimicrobials and injectable preparations were prescribed judiciously. The number of investigations requested during the first visit was highest in medicine (1-12) and lowest in ophthalmology (1-2). The mean number of investigations for all five departments (2.7) decreased considerably from the first to the second visit. About 87% of the prescribed drugs were dispensed from the hospital pharmacy. The average dispensing time was 340 seconds per patient and all the dispensed drugs were adequately labelled. However, only 46% of patients/attendants were aware of the correct dose of the various drugs procured from the pharmacy. This study reveals that there is scope for improvement in patient care indicators in areas of rational prescribing in the hospital.
Pranidipine, a long-acting 1,4-dihydropyridine-type calcium channel blocker, enhances nitric oxide-induced relaxation. In the present study, the effects of pranidipine on the survival of salt-sensitive Dahl rats were evaluated. Dahl rats were divided into three groups of 20 animals each and assigned to pranidipine at doses of 3 and 10 mg/kg once daily and vehicle, Arabic gum (control). The rats were loaded with an 8%-NaCl diet at 8 weeks, and simultaneously started drug treatment, which continued until all animals of the control group were dead. Systolic blood pressure was initially around 110 mm Hg, and became about 190 mm Hg at 8 weeks after salt-loading, and kept at higher levels in the control group. However, the blood pressure increase was completely inhibited by pranidipine treatment. In the control group, all animals were dead at 19 weeks after salt-load, while there was no death in the pranidipine-treated groups.
We investigated the effects of administration of non-hypotensive doses of ATP-sensitive K + channel (K A T P ) openers (nicorandil and celikalim), and a specific mitochondrial K A T P channel blocker (5-hydroxydecanoate) prior to and during coronary occlusion as well as prior to and during post-ischemic reperfusion on survival rate, ischemia-induced and reperfusion-induced arrhythmias and myocardial infarct size in anesthetized albino rabbits. The thorax was opened in the left 4th intercostal space and after pericardiotomy the heart was exposed. In Group I, occlusion of the left main coronary artery and hence, myocardial ischemia- induced arrhythmias were achieved by tightening a previously placed loose silk ligature for 30 minutes. In Group II, arrhythmias were induced by reperfusion following a 20 minute ligation of the left main coronary artery. Both in Group I and Group II, early intravenous infusion of nicorandil (100 μg/kg bolus + 10 μ/kg/min) or celikalim (0.2 μg/kg/min) just prior to and during ischemia increased survival rate (75% & 67% vs 60% in the control subgroup in Group I; 86% & 75% vs 55% in the control subgroup in Group II), significantly decreased the incidence and severity of life-threatening arrhythmias and significantly decreased myocardial infarct size. However, late intravenous administration of nicorandil or celikalim at the onset and during reperfusion did not increase survival rate nor confer any antiarrhythmic or cardioprotective effects. The antiarrhythmic and cardioprotective effects of both nicorandil and celikalim were abolished by pretreating the rabbits with 5-hydroxydecanoate (5 mg/kg, i.v. bolus), a selective mitochondrial K A T P channel blocker. In the present study, higher levels of malondialdehyde (MDA) and lower levels of reduced glutathione (GSH) and superoxide dismutase (SOD) in the necrotic zone of of the myocardium in all twelve subgroups of Group II suggest little anti-free radical property of nicorandil and celikalim. In conclusion, intervention by intravenous administration of nicorandil and celikalim (through the selective activation of mitochondrial K A T P channels), increased survival rate and exhibited antiarrhythmic and cardioprotective effects during coronary occlusion and reperfusion in anesthetized rabbits when administered prior to and during coronary occlusion.
Human granulocyte colony-stimulating factor (hG-CSF) is one of the hematopoietic factors that controls the differentiation of pluripotent stem cells in many types of blood cells during hematopoiesis. It also plays a key role in the stimulation of proliferation and differentiation of several types of blood cells including granulocytes and macrophages. This study examined the effects of recombinant hG-CSF (rhG-CSF) on the recovery of peripheral neutrophil number, DNA damage of peripheral blood and the survival rate of mice that received whole-body X-ray irradiation. rhG-CSFs were prepared by replacing the respective Met 1 7 with Ser 1 7 , Ala 1 7 , and Gly 1 7 . [Ser 1 7 ] G-CSF, [Ala 1 7 ] G-CSF and [Gly 1 7 ] G-CSF (10 μg/kg) each were administered subcutaneously to X-ray-irradiated mice for 21 days after the bone marrow transplantation. Treatment of rhGCSF increased the neutrophil differentiation significantly. Peripheral neutrophil number and the ratio of myloid to erythoid in the bone marrow gradually recovered to the normal level from the 13th day. [Ser 1 7 ] G-CSF-treated group was significantly different compared with the vehicle-treated group, and [Ala 1 7 ] G-CSF and [Ser 1 7 ] G-CSF-treated groups showed the highest levels on the 17th and 21st day, respectively. The mortality of [Ser 1 7 ] G-CSF-treated group was the lowest compared to approximately 30% death rate of the vehicle-treated group. Moreover, on the average, micronucleus (MN) frequencies of all treated groups tended to decrease gradually from the 9th to the 25th day. MN frequencies of [Ser 1 7 ] G-CSF and [Ala 1 7 ] G-CSF-treated groups were significantly lower than those of the vehicle control group (p < 0.05) from the 13th day. This observation suggests that methionyl-free rhG-CSF might have a protective role in severely irradiated mice and application of [Ser 1 7 ] G-CSF hastened the recovery of leukocytes and neutrophils in peripheral blood.
Systemic and splanchnic hemodynamics were measured during the infusion of adenosine (ADO) in conscious and normotensive Sprague-Dawley rats using the radioactive microsphere technique. The effects of ADO were shown in a dose-dependent fashion. Under 100 mu g/kg/min of intravenous ADO administration, systemic hemodynamic parameters and organ blood flow did not change significantly. The higher dose, 500 mu g/kg/min, rapidly reduced the mean arterial pressure from 113 +/- 7 to 83 +/- 5 mmHg (25%, p < 0.001) due to a reduction of total peripheral resistance from 0.82 +/- 0.13 to 0.60 +/- 0.09 mmHg/min/ml (27%, p < 0.001). Cardiac output remained unchanged because of a decrease in heart rate from 411 +/- 14 to 355 +/- 14 beats/min (14%, p < 0.001). ADO also significantly increased blood flows to the heart, esophagus, stomach, small intestine, mesentery, hepatic artery and portal vein. The increased magnitude ranged from 100 to 400%. The esophagus demonstrated the greatest increase in the blood flow. No change was observed in the brain, lungs, kidneys, colon and testis. The blood flow decreased in the spleen. ADO receptor antagonist, 8-(p-sulfophenyl) theophylline, significantly attenuated the ADO-induced hypotensive response mediated by A(2) receptors, and the negative chronotropic effect mediated by A(1) receptors. Therefore, ADO is possibly a potent vasodilator in the splanchnic organs, especially in the gastrointestinal tract.
Cimetidine, a histamine Hz-receptor antagonist, has been reported to reduce the metabolism of several drugs including quinine by inhibition of the hepatic mixed-function oxidase enzyme system which is responsible for drug biotransformation. Since mefloquine is a chemically structural analog of quinine, the purpose of this study is to explore whether cimetidine affects mefloquine pharmacokinetics following orally coadministered cimetidine in a way similar to quinine. The pharmacokinetics of mefloquine (a single 500-mg oral dose) in 10 healthy male volunteers before and after a 28-day course of cimetidine (800 mg.day(-1)) orally coadministered was designed for the study. Blood samples for plasma mefloquine concentrations before and after cimetidine was collected for the 28-day period. The mean peak plasma mefloquine concentration (C-max), time to peak concentration (t(max)) and area under the plasma concentration-time curve (AUG) before cimetidine treatment (556.46 +/- 117.41 mu l(-1), 12.54 +/- 7.35 h, and 225.18 +/- 109.76 mg.h.l(-1), respectively) were not significantly altered (p > 0.05) after cimetidine (569.14 +/- 120.12 mu g.l(-1), 7.46 +/- 2.41 h, and 308.75 +/- 144.93 mg.h.l(-1), respectively), while there were significant reduction (p < 0.05) in the apparent oral clearance (CLO) (0.051 +/- 0.026 versus 0.031 +/- 0.015 1.h(-1).kg(-1)) and a significant increase (p < 0.05) in the elimination half-life (t(1/2)) after cimetidine treatment (9.6 versus 14.4 days, respectively). Therefore, the present data suggest that cimetidine reduces the the CLO and prolongs the elimination t(1/2) of mefloquine in a manner similar to quinine.
Tetrandrine is a calcium channel antagonist with reported anti-hypertensive effect. However, the potential role of tetrandrine as a therapeutic agent in portal hypertension has yet to be explored. The present study aimed To investigate the chronic effects of two calcium channel antagonists, tetrandrine and verapamil, on the portal pressure of portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Animals were allocated into one of the two groups: tetrandrine group and verapamil group. Tetrandrine group was sub-divided into 10, 30, 50 mg/kg and vehicle (0.1 N HCl) subgroups. Verapamil group was sub-divided into 10, 30, 50 mg/kg and vehicle (saline) subgroups. Drug or vehicle was administered by gavage every 12 hours for 9 consecutive days, starting 2 days before ligation and continuing thereafter. After 9 days of tetrandrine treatment, portal venous pressure was significantly reduced in the subgroups receiving 30 and 50 mg/kg (12.6 +/- 0.3 mmHg, p < 0.05 and 9.7 +/- 0.6 mmHg, p < 0.01 vs. vehicle, respectively) as compared to vehicle group (14.1 +/- 0.6 mmHg). Mean arterial pressure was reduced only in the subgroup receiving the highest dose. There was no difference in body weight or heart rate between the vehicle and any tetrandrine subgroup. After 9 days of verapamil treatment, portal venous pressure was significantly reduced in the subgroups receiving 30 and 50 mg/kg (12.1 +/- 0.5 mmHg, p < 0.05 and 11.9 +/- 0.6 mmHg, p < 0.01 vs. vehicle, respectively) as compared to vehicle group (14.2 +/- 0.4 mmHg). Mean arterial pressure and heart rate were reduced only in the subgroup receiving the highest dose. There was no difference in body weight between the vehicle and any verapamil subgroup. Our results showed that chronic treatment of tetrandrine or verapamil reduced portal Venous pressure in portal hypertensive rats.
Plasma glucose and total lipid levels in normal and streptozotocin-diabetic rats were determined after oral administration of a water extract of Pandanus odorus Ridl. root. The oral administration of the water extract at doses of 0.25, 0.5 and 1 g kg(-1) produced a significant hypoglycemic effect in the intravenous glucose tolerance test and the adrenaline hyperglycemic test. Plasma non-esterified fatty acids were significantly decreased after 1 and 2 hours of single oral administration of the Pandanus extract at doses of 0.25 and 0.5 g kg(-1). Plasma cholesterol and triglyceride were also significantly decreased by the extract after once daily oral administration of Pandanus extract at a dose of 0.5 g kg(-1) for 7 days. These results suggest that a water extract of Pandanus odorus has hypoglycemic and hypolipidemic effects in streptozotocin-diabetic rats.
In an earlier publication, we have characterized the opioid receptors of the spinal cord involved in cardiovascular regulation. It is still not clear whether the inhibition of cardiovascular functions is mediated by pre/post synaptic opioidergic receptors. In the present study we have investigated the effect of guanethidine pretreatment of spinal autonomic loci on the cardiovascular effects of intrathecally administered morphine, ketamine and pentazocine. Intrathecal injection of morphine, pentazocine and ketamine induced dose related bradycardia and hypotension. Intrathecal injection of guanethidine (500 mu g) induced fall in blood pressure and heart rate. In animals where the effect of guanethidine was fully manifested, the effect of intrathecal injection of opioidergic agonists was completely blocked, It is therefore concluded that the inhibitory opioid receptors (mu and sigma) through which these agonists induce hypotension and bradycardia are probably located presynaptically on the facilitatory catecholaminergic neurones impinging upon the sympathetic preganglionic neurones (SPN).
