Effect of moxonidine on drug induced cardiac arrhythmias and its possible antinociceptive effect in rats

Moxonidine is a new second generation, centrally acting antihypertensive drug. It causes peripheral sympathoinhibition, triggered at the level of central nervous 11-receptors. The present study was designed to screen various cardiovascular effects of moxonidine both in-vivo and in-vitro as well as to investigate the possible analgesic effect of moxonidine. In-vitro results revealed that moxonidine produced dose related inhibition of the force of contraction of the isolated perfused rabbit's heart. A vagal like action was suggested because both muscarinic and nicotinic receptors antagonist abolished this effect. In vivo results showed that acute intravenous injection of moxonidine significantly reduced heart rate of normotensive rats dose dependantly. Moxonidine in different doses exhibited pronounced antiarrhythmic effects characterized by dose-dependent increase in adrenaline arrhythmogenic dose and significant decrease in the number of extrasystoles. Furthermore, moxonidine in different doses, increased both the arrhythmogenic and ventricular fibrillatory doses of ouabain in a dose-dependent manner. Lastly, acute moxonidine administration was found to provide potent antinociceptive efficacy in control of acute pain in rats and yohimbine, was able to antagonize this effect

Effect of amlodipine, fosinopril and atenolol on glucose metabolism and microalbuminuria in STZ diabetic rats

This study compares the effect of a calcium channel blocker [amlodipine], an ACE inhibitor [fosinopril] and a B 1-blocker [atenolol] on blood glucose level, plasma insulin level, insulin sensitivity and 24 hours urinary albumin excretion in groups of rats made diabetic by a single intraperitoneal injection of streptozotocin [STZ] [60 mg/kg]. Five groups of rats were used in this work. The first group [control non-diabetic rats] was normoglycemic with blood glucose level 116.8 +/- 9.4 mg/dl and 24 hour[H] urinary albumin 8.2 +/- 1.2 mg/24 H urine. The other four groups were made diabetic by a single dose of STZ. The second group [control non-treated diabetic rats] exhibited hyperglycemia 8 weeks after induction of diabetes with blood glucose level 354 +/- 32.6 mg/dl, plasma insulin level 10.1 +/- 0.8 mIU/ml and 24 H urinary albumin 42.6 +/- 3.2 mg/24 H wine. Results of this study revealed that amlodipine oral administration in a dose of 5 mg/kg for 8 weeks in the third group of STZ diabetic rats induced a significant reduction of blood glucose level [234 +/- 18.6 versus 354 +/- 32.6 in control diabetic rats, P< 0.05] and plasma insulin level [8.2 +/- 06 mIU/ml versus 10.1 +/- 0.8 mIU/ml in control diabetic rats, P<0.05]. Amlodipine also caused significant reduction in 24 H urinary albumin [18.2 +/- 1.2 mg versus 42.6 +/- 3.2 mg in control diabetic rats, P<0.05] and significant improvement in sensitivity to intraperitoneal bolus dose of insulin where it caused a significant reduction in blood glucose level at 0.5 H,1 H and 6 H after insulin compared to control diabetic rats, P<0.05. The results of this study also revealed that administration of fosinopril in a dose of 5 mg/kg/day oral to the fourth group of STZ diabetic rats for 8 weeks induced a significant reduction in blood glucose level plasma insulin level, and 24 H urinary albumin excretion compared to control non-treated diabetic rats. Fosinopril, also produced a significant improvement in insulin sensitivity at 0.5 H, 1 H and 6 H after insulin injection compared to control non-treated diabetic rats. In contrast, atenolol given orally in a dose of 10 mg/kg/day for 8 weeks to fifth group of diabetic rats did not induce a significant change in blood glucose level, plasma insulin level and 24 H urinary Albumin and even reduced insulin sensitivity compared to control non-treated diabetic rats. It could be concluded from these results that both amlodipine and fosinopril are better antihypertensives than atenolol in diabetic patients as they improved glucose tolerance and albuminuria in STZ diabetic rats

Cardiac and renal protective effects of L-carnitine in hypercholesterolemic rats

This work was carried out in order to investigate the role of L-carnitine in protection against acute myocardial infarction as well as acute renal failure induced experimentally in hypercholesterolemic rats. Hypercholesterolemia was induced by feeding rats 5% cholesterol enriched diet for 30 days. The study included two main parts. In the first part, isoprenaline HCI was used [300 mg/kg I.P.] to induce acute myocardial infarction in rats. The results of this part revealed that, hypercholesterolemia significantly increased all the parameters which evaluate the cardiac necrosis [T wave voltage, CPK level and infarct size%]. Daily administration of L-carnitine [200 mg/kg orally] for 30 days induced significant decrease in serum total cholesterol, TG, LDL as well as significant decrease in all the indices of cardiac necrosis when compared to their corresponding values in the rats fed 5% cholesterol enriched diet but not treated with L-carnitine. In the second part of the study, acute renal failure was induced in rats by 1.M. injection of hypertonic glycerol [50%] in a dose of 10 ml/kg. The results of this part showed that hypercholesterolemia significantly aggravated the acute renal failure induced by glycerol. Daily administration of L-carnitine for 30 days normalized the lipid perofile [total cholesterol, TG, LDL and HDL] and significantly decreased serum urea, creatinine, Na+ and K+ compared to their corresponding values in Lcarnitine non treated glycerol injected rats. All the results of this work were also confirmed by the histopathologicat exmination of the hearts and kidneys of the tested rats. So, it may be concluded that 1- Hypercholesterolemia aggrevates the acute myocardial infarction as well as the acute renal failure induced experimentally in rats. 2- Daily administration of Lcarnitine for 30 days normalizes the lipid profile of the rats fed cholesterol enriched diet. 3- L-carnitine administration provides an evident cardiac and renal protective effects, 4- The cardioprotective and renoprotective effects of L-carnitine may be attributable to its lipid lowering and antioxidant effects and/or its role in improving fatty acids metabolism and energy production at the mitochondrial level

Protective effect of valsartan and lacidipine on acute myocordial infarction in hypercholesterolemic rabbits

The present work was conducted to study the cardioprotective effects of long term administration of two antihypertensive drugs namely valsartan, a specific AT 1 blocker, and lacidipine, a dihydropyridine calcium antagonist, in male rabbits fed high cholesterol diet for two months. Their actions on the Serum creatine phosphokinase [CPK], lipid profile, total cholesterol [T.ch], triglycerides [T.G], low density lipoprotein [LDL], high density lipoprotein [HDL] and their actions on aorta and the infarct size of atherosclerotic rabbits were investigated. Male rabbits were rendered atherosclorotic by feeding cholesterol in a daily dose of 100 mg/kg for 2 months. Over the same period of cholesterol feeding, rabbits were treated with either valsartan [20 mg/kg orally] or lacidipine [3 mg/kg/day orally]. At the end of the two months, rabbits were subjected to coronary artery ligation [LAD] for 4 hours. Three parameters were studied namely electrophysiological parameter recording S-T segment elevation using electrocardiogram, biochemical parameter recording plasma CPK before and after 4 hours of ligation of LAD and histochemical parameter [staining heart sections with triphenyl tetrazolium [TPT] 4 hours after ligation of LAD and the infarct areas were computed, in addition histopathological changes in aorta were studied. In this study both valsartan and lacidipine decreased significantly S- T segment elevation after LAD ligation compared to the atherosclerotic group. Also both drugs significantly decreased the rise in CPK level 4 hours after ligation of LAD compared to the atherosclerotic group at the same time interval. Both of them decreased the infarct size significantly compared to the atherosclerotic group. Moreover lacidipine, but not valsartan improved lipid profile of atherosclerotic animals, but both drugs improved histopathological changes in aorta. From all the results of this study it can be concluded that both valsartan and lacidipine can be used in acute myocardial infarction to limit the infarct size. Long term adminstration of both drugs is effective and of great value in decreasing the incidence of myocardial infraction or decreasing its size. Since both drugs inhibited development of atherosclerosis on long-term administration which is a major risk factor in development of coronary heart disease, so both drugs are efficient prophylactic agents in patients liable to atherosclerosis and coronary heart diseases