Sodium acetate prevents nicotine-induced cardiorenal dysmetabolism through uric acid/creatine kinase-dependent pathway.

BACKGROUND: Cigarette smoking or nicotine replacement therapy has been associated with cardiometabolic disorders (CMD). Hyperuricemia has been implicated in the pathogenesis of CMD and cardiorenal dysfunction. Gut microbiota-derived short chain fatty acids (SCFAs) have been reported to have beneficial glucoregulatory and cardiorenal protective effects. This study aimed at investigating the effect of acetate, a gut-derived SCFA, on nicotine-induced CMD and associated cardiorenal dysmetabolism. MATERIALS AND METHOD: Twenty-four male Wistar rats (n = 6/group) were grouped as: vehicle (p.o.), nicotine-exposed (1.0 mg/kg; p.o.), and sodium acetate-treated (200 mg/kg; p.o.) with or without nicotine exposure daily for 6 weeks. Glucose regulation was evaluated by oral glucose tolerance test and homeostatic model assessment of insulin resistance. Cardiac and renal triacylglycerol (TG), lactate, nitric oxide (NO), uric acid (UA) levels, lactate dehydrogenase (LDH), creatine kinase (CK), adenosine deaminase (ADA), and xanthine oxidase (XO) activities were measured. RESULTS: The CMD were confirmed in the nicotine-exposed rats that exhibited lower body weight, insulin resistance, endothelial dysfunction, glucose intolerance, increased cardiac and renal TG, TG/HDL-cholesterol, UA, lactate, lipid peroxidation, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, LDH, CK, ADA and XO activities. Concurrent treatment with acetate prevented nicotine-induced glucometabolic and cardiorenal alterations. CONCLUSION: In summary, these results implied that nicotine exposure caused glucometabolic dysregulation and surplus lipid deposit in the heart and kidney through increased UA production and CK activity. Therefore, oral acetate administration prevents cardiorenal lipotoxicity and glucometabolic dysregulation via suppression of UA production and CK activity in nicotine-exposed rats.

Blockade of mineralocorticoid receptor ameliorates oral contraceptive-induced insulin resistance by suppressing elevated uric acid and glycogen synthase kinase-3 instead of circulating mineralocorticoid.

Context: Estrogen-progestin combined oral contraceptive (COC) has been connected to mineralocorticoid receptor (MR) activation and adverse cardiometabolic events. We consequently hypothesised that insulin resistance (IR), hyperuricemia, and elevated circulating GSK-3 induced by COC is through activation of MR via mineralocorticoid and glucocorticoid pathways.Methods: Female Wistar rats aged 12 weeks received (po) vehicle and COC (1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel) with or without MR blocker (0.25 mg/kg spironolactone; Spl), daily for eight weeks.Results: Data showed that COC treatment led to increased IR, 1-hour postload glucose level, insulinemia, triglyceride/HDL-cholesterol ratio, total cholesterol/HDL-cholesterol ratio, uric acid, GSK-3, aldosterone, corticosterone values, impaired glucose tolerance and pancreatic ß-cell function. However, MR blockade by Spl ameliorated all these alterations except that of aldosterone.Conclusion: The results demonstrate that COC induces IR, hyperuricemia and high GSK-3 levels through activation of MR via glucocorticoid dependent pathway.

Sodium acetate protects against nicotine-induced excess hepatic lipid in male rats by suppressing xanthine oxidase activity.

Fatty liver is the hepatic consequence of chronic insulin resistance (IR) and related syndromes. It is mostly accompanied by inflammatory and oxidative molecules. Increased activity of xanthine oxidase (XO) exerts both inflammatory and oxidative effects and has been implicated in metabolic derangements including non-alcoholic fatty liver disease. Short chain fatty acids (SCFAs) elicit beneficial metabolic alterations in IR and related syndromes. In the present study, we evaluated the preventive effects of a SCFA, acetate, on nicotine-induced dysmetabolism and fatty liver. Twenty-four male Wistar rats (n = 6/group): vehicle-treatment (p.o.), nicotine-treated (1.0 mg/kg; p.o.), sodium acetate-treated (200 mg/kg; p.o.) and nicotine + sodium acetate-treated groups. The treatments lasted for 8 weeks. IR was estimated by oral glucose tolerance test and homeostatic model assessment of IR. Plasma and hepatic free fatty acid, triglyceride (TG), glutathione peroxidase, adenosine deaminase (ADA), XO and uric acid (UA) were measured. Nicotine exposure resulted in reduced body weight, liver weight, visceral adiposity, glycogen content and glycogen synthase activity. Conversely, exposure to nicotine increased fasting plasma glucose, lactate, IR, plasma and hepatic TG, free fatty acid, TG/HDL-cholesterol ratio, lipid peroxidation, liver function enzymes, plasma and hepatic UA, XO and ADA activities. However, plasma and hepatic glucose-6-phosphate dehydrogenase-dependent antioxidant defense was not affected by nicotine. Concomitant treatment with acetate ameliorated nicotine-induced effects. Taken together, these results indicate that nicotine exposure leads to excess deposition of lipid in the liver by enhancing XO activity. The results also imply that acetate confers hepatoprotection and is accompanied by decreased XO activity.

Antiseizure Effects of Ketogenic Diet on Seizures Induced with Pentylenetetrazole, 4-Aminopyridine and Strychnine in Wistar Rats.

The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ), 4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. Serum ketosis was significantly higher in MCT-KD-fed rats (12.7 ±2.6) than ND-fed (5.17±0.86) rats. Fasting blood glucose was higher in ND-fed rats (5.3±0.9mMol/l) than in MCT-KD fed rats (5.1±0.5mMol/l) with p=0.9. Seizure latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after PTZ-induced seizures (61±9sec vs 570±34sec) and AP-induced seizures (49±11sec vs 483±41sec). The difference after Str-induced seizure (51±7 vs 62±8 sec) was not significan. The differences in seizure duration between ND-fed and MCT-KD fed rats with PTZ (4296±77sec vs 366±46sec) and with AP (5238±102sec vs 480±67sec) were significant (p<0.05), but not with STR (3841±94sec vs 3510±89sec) respectively. The mean serum Na+ was significantly higher in MCT-KD fed (141.7±2.1mMol/l) than ND-fed rats (137±2.3mMol/l). There was no significant difference in mean values of other serum electrolytes between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to PTZ-and AP-induced seizures, but has no effect on STR-induced seizures. This antiseizure property is probably mediated through GABAergic receptors (PTZ effect) and blockade of membrane bound KATP channels (AP effect) with some enhancement by serum ketosis.

Antimalarial Activity of Cocos nucifera Husk Fibre: Further Studies.

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties of Cocos nucifera were evaluated in vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25-500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active against Plasmodium falciparum W2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was active in vivo against Plasmodium berghei NK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P > 0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P < 0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles.

Analgesic, anti-inflammatory and antipyretic effects of the ethanol extract of Acalypha wilkesiana leaves in rats.

The leaves of Acalypha wilkesiana are commonly used for the treatment of pain, fever and ulcer by traditional medical practitioners without any scientific data to evaluate the appropriateness of some of the practices. Therefore, this study was carried out to determine whether the ethanol extract of Acalypha wilkesiana has analgesic, anti-inflammatory and antipyretic as well as anti-ulcer effects. The hot plate latency assay and formalin- induced paw licking models were used to evaluate analgesic effects. Animals were divided into groups comprising of five rats each. There were control (administered saline) and reference (administered indomethacin) groups. Also there were three extract groups administered 25, 50 or 100 mg/Kg body weight of extracts. Ulcer was induced using absolute ethanol followed by pylorus ligation in all animals; inflammation was induced using carrageenan while pyrexia was induced by injecting brewer's yeast intramuscularly into the dorsal part of the abdominal cavities of the rats. Different sets of rats were used for the anti-ulcer, anti-inflammatory and antipyretic studies although animal grouping for extract administration were as in analgesic studies. The results show that the extract produced dose-dependent and significant (p<0.05) analgesic and anti-inflammatory activities. The extract also significantly protected against ethanol induced ulcer. Likewise, the extract significantly (p<0.05) reduced the pyretic states of the animals. This study has therefore further provides evidences that may support the ethnomedicinal uses of the ethanolic extracts of Acalypha wilkesiana leaves.

Effects of chronic treatment with cyclooxygenase inhibitor, indomethacin on oral contraceptive-induced high blood pressure in female rats.

The present study sought to investigate the effects of prostaglandins synthesis inhibition with indomethacin on blood pressure, heart rate, cardiac weight, plasma electrolytes and cardiovascular responses to arterial baroreceptor stimulation in Oral contraceptive (OC) treated female Sprague-Dawley rats. Oral administration of synthetic oestrogen, ethinyl oestradiol in combination with progestogen, norgestrel for ten weeks significantly increased blood pressure and cardiac weight compared with those of the control rats. Concomitant treatment with indomethacin significantly abrogated increase in blood pressure but did not affect the increase in cardiac weight induced by OC. Heart rate, plasma sodium and potassium concentrations were not affected by OC and/or indomethacin treatment. OC treatment did not alter sympathetic-mediated pressor and tachycardiac responses caused by bilateral carotid baroreceptors unloading. However, these responses were significantly attenuated by indomethacin treatment. These results demonstrated that rat model of OC-induced high blood pressure developed cardiac hypertrophy that is not associated with altered sympathetic-mediated cardiovascular responses to arterial baroreceptor stimulation. The finding that indomethacin prevented OC-induced high blood pressure, but not associated cardiac hypertrophy implies that synthesis of prostaglandins may be an important determinant of OC-induced hypertension, while associated cardiac hypertrophy may not be pressure overload-dependent.

Effect of increased dietary calcium on body weight, food and water intake in oral contraceptive treated female rats.

The effects of high calcium diet on body weight in OC treated rats are unknown. This study therefore investigated the effect of increasing dietary calcium from 0.9% to 2.5% on body weight, food ingestion, water intake, heart weight index and renal weight index in female Sprague-Dawley rats treated with a combination of OC steroids (ethinyloestradiol + norgestrel). The rats were assigned into three groups of average of 11 rats each; control, OC-treated and OC + Calcium – treated groups and administered orally for 10 weeks. Food and water intake, body weight, cardiac weight index, left ventricular weight index, renal weight index and serum calcium level were determined. The result shows that OC treated rats had significantly lower serum calcium concentration, body weight gain, food, water and calcium intake than those of the control rats. The OC + Calcium – treated rat had significantly higher serum calcium concentration, food, water and calcium intake but significantly lower body weight than those of the OC - treated rats. OC + Calcium - treated rats had significantly higher water intake, calcium intake and significantly lower body weight and food intake when compared with the control rats. Cardiac weight index and renal weight index was comparable in all groups. In conclusion, combined OC-induced reduction in weight gain might be associated with inhibition of the feeding center and consequent inhibition of the thirst center. Co-administration of dietary calcium augmented the reduction in weight gain seen in OC-treated rats probably by further suppression of the feeding and thirst centers.

Oral contraceptive-induced high blood pressure is prevented by renin-angiotensin suppression in female rats but not by sympathetic nervous system blockade.

The use of oral contraceptive (OC) steroids is associated with high blood pressure, although mechanisms responsible are still unclear. This study sought to investigate the possible roles that renin-angiotensin system (RAS) and sympathetic nervous system (SNS) may play in the development of OC-induced hypertension. Administration of OC led to significant increases in blood pressure, heart weight and significant decrease in urinary output in OC-treated and OC+clonidine-treated groups but not in OC+captopril-treated group. The pressor response to angiostensin II was significantly greater in the OC-treated rats than in the control rats. However, the pressor responses induced by norepinephrine were not significantly affected by OC administration. The results of the present study demonstrate that OC-induced high blood pressure is associated with cardiac hypertrophy, enhanced pressor response to angiotensin II and preserved pressor response to sympathetic activation. The study also suggests that the development of the OC-induced hypertension and cardiac hypertrophy is mediated by RAS, but not by SNS.

Oral contraceptive administration aggravates nitric oxide synthesis inhibition-induced high blood pressure in female rats.

UNLABELLED: The use of estrogen-progestogen oral contraceptive (OC) is associated with high blood pressure, although mechanisms responsible are still unclear. This study sought to investigate the effects of administration of OC on high blood pressure resulting from nitric oxide (NO) synthesis inhibition in female Sprague-Dawley rats. Rats were given ethinyl estradiol in combination with norgestrel and were treated with NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME) in the drinking water or drinking water alone for 6 weeks. OC treatment alone led to a significant increase in blood pressure and positive water balance. Treatment with l-NAME alone resulted in a significant elevation of blood pressure without significant positive water balance. Concomitant treatment with OC and l-NAME produced significant increases in blood pressure and water balance. These magnitudes of increases were significantly greater than those observed in rats treated with OC or l-NAME alone. Treatment with OC did not affect NO biosynthesis with or without concurrent l-NAME treatment. Treatment with OC and/or l-NAME did not significantly affect body weight, food intake, heart rate, cardiac weight/body weight ratio, plasma sodium, glomerular filtration rate and urinary sodium output. CONCLUSION: These data demonstrate that OC administration resulted in a modest increased blood pressure via enhanced water retention that was not associated with impaired NO synthesis. On the other hand, these results showed that increased blood pressure induced by inhibition of NO synthesis was not associated with water retention. The study also indicated that OC administration aggravated increase in blood pressure during NO synthesis inhibition, via enhanced water retention.

Effect of dietary magnesium on glucose tolerance and plasma lipid during oral contraceptive administration in female rats.

Studies that associated oestrogen-progestogen oral contraceptive (OC) use with altered glucose and lipid metabolisms in women did not account for possible influence in dietary magnesium. The use of OC and glucose and lipid metabolism seems to remain a broad public health concern since over 100 million women use OC world wide for a prolonged period of time. The study, therefore, sought to investigate in a female rat model whether or not glucose intolerance and dyslipidaemia associated with OC are influenced by dietary magnesium status. Control and OC- treated rats were maintained on control diet, whereas OC+ Mg- treated rats were on high magnesium diet. OC- treated and OC+Mg treated rats also received a combination of OC steroids, ethinyl oestradiol and norgestrel (orally). When compared with the controls, OC treatment led to significant reduced glucose tolerance and plasma HDL-cholesterol and significant increases in plasma LDL-cholesterol and atherogenic indices in OC- treated rats. Treatment with OC did not result in significant attenuation in these parameters in OC+Mg- treated rats when compared with the controls. In conclusion, these results suggest that impaired glucose tolerance and dyslipidaemia associated with OC use may be prevented by increased dietary magnesium.

Low dietary folate impairs glucose tolerance and plasma lipid profile in oral contraceptive-treated rats.

UNLABELLED: Estrogen-progestogen oral contraceptive (OC) use is associated with abnormal lipid metabolism, impaired glucose tolerance and high prevalence of vascular complications. OC use has been shown to alter the requirements for folic acid. Therefore, the aim of the present study was to clarify the influence of dietary folic acid on OC-induced impaired glucose tolerance and abnormal plasma lipid profile in female Sprague-Dawley rats. Vehicle-treated and OC-treated rats were fed for 6 weeks with a control diet (750mug folic acid/kg diet) while OC-treated folic acid deficient (FD) rats were fed for 6 weeks with a folic acid-deficient diet (250mug folic acid/kg diet). OC receiving rats were treated with a combination of OC steroids (ethinyl estradiol and norgestrel) by oral gavage. OC treatment resulted in rats receiving folic acid deficient diet in impaired glucose tolerance, decreased high-density lipoprotein (HDL)-cholesterol and increased low-density lipoprotein (LDL)-cholesterol when compared with control rats. However, OC treatment did not result in impaired glucose tolerance or disturbed plasma lipid profile in rats receiving the same folic acid level as the controls. OC treatment led to significant decreases in plasma levels of 17beta-estradiol and testosterone in both groups. OC administration in rats with folic acid deficient diet significantly lower HDL-cholesterol and higher LDL-cholesterol levels while plasma levels of 17beta-estradiol and testosterone were similar in both OC-treated groups. CONCLUSION: These results demonstrate impaired glucose tolerance and disturbed plasma lipid profile induced by OC treatment in folic acid deficient rats and suggest that inadequate folic acid intake might contribute to increased cardiovascular risk during OC use that could be prevented by proper oral folic acid intake.

Effect of photoperiod on testicular functions in male Sprague-Dawley rats.

Variation in reproductive status in response to photoperiods has been observed in laboratory rats. We investigated the effects of photoperiod on testicular activity in Sprague-Dawley rats (Rattus norvigicus) maintained in experimental photoperiodic condition. Twenty-four adult male rats weighing 170+/-10g were conditioned to different lighting conditions of Light/Dark (LD) Cycle for 6 weeks. Group 1, Control group (LD12:12, light on from 07:00hr to 19:00hr). Group 2, Short Photoperiod group (LD 8:16hr, light on from 09:00hr to 17:00hr). Group 3, Long Photoperiod group (LD 16:8hr, light on from 05:00hr to 21:00hr). A significant influence of different lighting conditions on the testicular parameters was observed. Short photoperiod showed a suppressing effect (P < 0.001) on testicular weight, sperm motility sperm viability and sperm counts, while long photoperiod had an inducing, though insignificant, effect on the measured parameters. The results confirmed that Sprague-Dawley rats are photoresponsive and changes in the photoperiod could influence their reproductive functions.

Effects of chronic administration of vitamin E on haemodynamic responses to postural stress or cold pressor test in apparently healthy young men.

OBJECTIVES: We sought to investigate the possible effect of chronic administration of vitamin E on haemodynamic responses to sympathetic stimulation and to test the hypothesis that chronic administration of vitamin E increases susceptibility to orthostatic intolerance. METHODS: Sympathetic stimulation was assessed by responses in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), forearm blood flow (FBF; venous occlusion plethysmography) and forearm vascular resistance (FVR) evoked by postural stress (600 head-up tilt; HUT) or cold pressor test (CPT) in 30 healthy young men before and after 4 weeks of vitamin E administration. CPT was induced by immersing a hand in water at 40 degrees C for 2 minutes. RESULTS: Administration of vitamin E reduced SBP (p<0.001), DBP (p<0.001), MAP (p<0.001), HR (p<0.001) and FVR (p<0.05) but increased FBF (p<0.01). Before vitamin E administration HUT increased HR (p<0.001). Conversely, HUT led to a decrease in HR (p<0.05) after vitamin E administration. The decreases in SBP (p<0.05) and FBF (p<0.05) with concomitant increases in DBP (p<0.001), MAP (p<0.001) and FVR (p<0.001) induced by HUT before vitamin E administration, were similar to those induced by HUT after vitamin E administration. The increases in SBP (p<0.001), DBP (p<0.001), MAP (p<0.001), HR (p<0.05), FVR (p<0.001) and a decrease in FBF (p<0.001) induced by CPT before vitamin E administration, were attenuated following vitamin E administration in these subjects. CONCLUSION: These results demonstrate that chronic administration of vitamin E significantly reversed HUT-induced tachycardia and prevented CPT-induced vascular and pressor responses. These findings suggest that vitamin E may exert cardioprotective effect presumably through enhanced cardiac vagal tone that may not be associated with poor orthostatic tolerance in young men.

Increased magnesium intake prevents hyperlipidemia and insulin resistance and reduces lipid peroxidation in fructose-fed rats.

UNLABELLED: Studies have suggested that type 2 diabetes mellitus is associated with abnormal lipid metabolism, oxidative stress and insulin resistance. Increased magnesium intake may improve dyslipidemia, oxidative stress and insulin insensitivity in type 2 diabetes. Therefore, the present study investigated the influence of increasing dietary magnesium from 0.1% to 1.0% for 4 weeks on plasma lipids, lipid peroxidation, l-ascorbic acid and insulin sensitivity in male Wistar rats fed a high-fructose diet. The rats were divided into control (CR), fructose-fed (FRU-fed) and fructose-fed supplemented with magnesium (FRU-Mg-fed) groups (n=8 per group). Homeostasis model assessment for insulin resistance (HOMA-IR) and plasma thiobarbituric acid-reactive substances (TBARS) were used as indices of insulin sensitivity and lipid peroxidation, respectively. When compared with controls, the FRU-fed group had significantly higher values of HOMA-IR, fasting plasma glucose, insulin, triglyceride, total cholesterol/HDL-cholesterol ratio (atherogenic index), and TBARS. Their values in FRU-Mg-fed group were close to those of the controls. FRU-Mg-fed group had also significantly higher plasma magnesium and l-ascorbic acid levels, but significantly lower LDL-cholesterol levels than those in control and Fru-fed groups. CONCLUSION: increased magnesium intake improved insulin sensitivity, hyperglycemia, hyperlipidemia and reduced lipid peroxidation in fructose-fed rats.

Effect of increased magnesium intake on plasma cholesterol, triglyceride and oxidative stress in alloxan-diabetic rats.

Cardiovascular disorders are the primary causes of morbidity and mortality in patients with diabetes mellitus (DM). Agents that improve lipid profile and reduce oxidative stress have been shown to reduce the ensuing risk factors. In the present study, we investigated whether increased magnesium intake could improve hyperglycaemia, dyslipidaemia, and reduce oxidative stress in alloxan-induced diabetic rats. Male Wistar rats were divided into non-diabetic (ND), diabetic (DM) and diabetic fed on a high magnesium diet (DM-Mg) groups. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were used as markers of oxidative stress. Plasma levels of ascorbic acid, magnesium and calcium were also determined. Diabetes was induced by injecting alloxan (100 mg/kg B.W). The fasting blood glucose levels were significantly lower in the DM-Mg rats than in the DM rats. Plasma total cholesterol, triglyceride, TBARS levels were significantly higher while plasma HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, ascorbic acid levels were significantly lowered in DM rats compared with the ND rats. Increased intake of magnesium significantly abrogated these alterations. There were no significant differences in the plasma levels of magnesium and calcium between the DM and ND groups. However, plasma levels of magnesium but not calcium were significantly elevated in DM-Mg rats when compared with other groups. In conclusion, these results suggest that diet rich in magnesium could exert cardioprotective effect through reduced plasma total cholesterol, triglyceride, oxidative stress and ameliorated HDL-cholesterol/total cholesterol ratio as well as increased plasma ascorbic acid and magnesium in diabetic rats.

The effect of nifedipine on oral contraceptive-induced hypertension in rats.

OBJECTIVE: Administration of oral contraceptive (OC) steroids is associated with an increased risk of developing hypertension, although the mechanisms underlying this effect are not well established. This study therefore sought to investigate the effect of L-type calcium channel blocker, nifedipine on OC-induced hypertension. METHODS: Female Sprague-Dawley rats received OC (norgestrel/ethinyloestradiol) and/or nifedipine orally for 10 weeks. . Blood pressure and heart rate were thereafter recorded under anaesthesia from the femoral artery with a Grass Polygraph 7D model, whereas plasma and urinary Na+ and K+ concentrations were measured using a flame photometer. The stable oxidation products of nitric oxide, urinary nitrite/nitrate (NO) were measured in urine by means of the brucine method. RESULTS: OC administration led to significant (p<0.05) increases in blood pressure and plasma Na+, and decreases in body weight, food and water consumption, excretion of Na+ and NO. Concomitant treatment with nifedipine significantly (p<0.05) abrogated the alterations induced by OC administration. CONCLUSION: This study provides evidence that the development of OC-induced hypertension is prevented by calcium channel blockade via improved renal handling of sodium and nitric oxide. The finding confirms the involvement of calcium channels in OC hypertension.

Effect of increased calcium intake on cardiac and vascular Na(+)-K(+)-ATPase activity in oral contraceptive-treated female Sprague-Dawley rats.

The present study aimed at investigating the influence of increased dietary calcium on Na(+)-K(+)-ATPase activity in heart and aorta of female Sprague-Dawley rats treated with oral contraceptive (OC) steroids. Rats were grouped as control (CR), OC-treated and OC+calcium-treated. OC-treated and OC+calcium-treated received a combination of OC steriods (ethinyloestradiol and norgestrel; ig). OC+calcium-treated rats were fed with 2.5% calcium diet, while OC-treated and CR groups were fed on 0.9% calcium diet. The activity of Na(+)-K(+)-ATPase in heart and aorta was significantly lower in OC-treated rats than those in the other groups. OC treatment caused significant increase in plasma glucose and significant decrease in plasma K+ as compared to control group. Decrease in Na(+)-K(+)-ATPase activity and plasma K+ was abrogated by increased calcium intake, while increase in plasma glucose was not normalized by calcium supplementation. Plasma levels of Na+, lipid peroxidation index and ascorbic acid were comparable among the three groups. These results showed that OC treatment could lead to impaired activity of cardiac and vascular Na(+)-K(+)-ATPase, possibly due to reduced plasma K+ level and these effects could be abolished by high calcium diet.

Haematological evaluation of ethanolic extract of Allium ascalonicum in male albino rats.

The haematological effect of ethanolic extract of Allium ascalonicum was evaluated in male albino rats during a 21 day administration at the doses of 50, 100 and 200 mg/kg b.w, orally. Parameters evaluated include the serum lipids, red and white cell indices. The results showed that the extract administered decreased most of the parameters relating to red cell and increased most of those parameters relating to white cells. It also decreased the total cholesterol (TCH), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) with no significant effect on the triglyceride levels.

Influence of carbon dioxide tension in the cephalic circulation on hind-limb vascular resistance in anaesthetized dogs.

In dogs anaesthetized with chloralose, the effects were determined of changes in cephalic blood PCO2 on vascular resistance and on the reflex vascular responses to stimulation of baroreceptors and chemoreceptors. Both vagus nerves were cut above the nodose ganglia, both carotid sinus regions were perfused with blood at controlled pressures and the cephalic circulation was perfused with blood, equilibrated with various levels of CO2, through the brachiocephalic and left subclavian arteries. Increases in cephalic blood PCO2 between 4 and 6 kPa resulted in increases in arterial perfusion pressure in a vascularly isolated hind limb. These responses were inhibited at high carotid sinus pressures and the responses to changes in carotid pressure were enhanced at high levels of cephalic PCO2. The reflex increase in vascular resistance resulting from stimulation of carotid chemoreceptors, however, was unaffected by the level of cephalic blood CO2. These results indicate that the carbon dioxide tension in the cephalic circulation is of importance in the control of vascular resistance in the hind limb.