Alteration of blood pressure response to arachidonic acid in diabetic rats

The dose dependency and mechanism of arachidonic acid [AA]-induced decrement in systemic blood pressure [BP] was investigated in diabetic rats, versus their controls: Intravenous [I.V.] injection of 0.5-2 mg AA into diabetic rats [2 weeks after a single S.C. injection of alloxan, 175 mg/kg] caused dose dependent decrement in BP. The diabetic rats displayed decreased responsiveness to the hypotensive effect of AA compared to control rats. AA hypotensive responses were completely abolished by indomethacin [5 mg/kg I.V.]. Prostaglandin F2gamma [PGF2gamma], 20 ug, and norepinephrine [NE], 4 ug, increased BP whereas acetyloholine [ACh], 2 ug, lowered it in both diabetic and control rats. No significant differences were detected for the effects of the above mentioned drugs between the two groups. The findings indicate that AA is converted into cyclo-oxygenase derived products with predilection to formation of excess vasoconstrictor[s] metabolites and/or depressed vasodilator[s] production

Adrenergic hyperresponsiveness of abrupt atenolol withdrawal: possible involvement of prostaglandins

Abrupt cessation of chronic B-adrenoceptor blockers administration has been advocated to result in a rebound phenomenon for which several mechanisms have been postulated. However, this study was designed to investigate the changes in cardiac and fat B-adrenergic receptors responsiveness and the possible involvement of prostaglandins in such changes after abrupt withdrawal of chronic atenolol therapy in normal albino rats. In the first part of the study heart rate [HR] and blood pressure [BP] responses were determined before and 2 and 5 minutes after intraperitoneal injection of isproterenol [isuprel] in a dose of 0.2 ug/kg. Isuprel administration to normal rats resulted in a significant increase in HR and BP, whereas atenolol administration for 21 or 24 days resulted in a significant decrease in HR and BP and obtunded the effect of isuprel administration. However, after 3 days of atenolol withdrawal significant increments in HR and BP were obtained. Isuprel injection, at this stage resulted in significant increases of HR and BP compared to their initial control or to their respective control values. In rats receiving indomethacin [15 mg/kg/day subcutaneously in 2 divided doses] during atenolol withdrawal period [3 days], BP was maintained at significantly low level, whereas HR retained its preatenolol level. Moreover, indomethacin resulted in significant inhibition of isuprel influence on HR and BP compared to control values. In the second part of the study the effect of atenolol withdrawal as well as the influence of isuprel on B[1] receptors of fat cells were determined through estimation of free fatty acids [FFA] in plasma of rats. In the control group isuprel infusion stimulated FFA release after 5,10 and 15 min. Atenolol administration for 21 or 24 days did not change basal FFA level, however, it blocked the isuprel stimulated release. Atenolol withdrawal did not affect FFA basal level, nevertheless, isuprel stimulated significantly FFA release. Furthermore, administration of indomethacin during atenolol withdrawal showed no effect on basal or isuprel stimulated release of FFA compared to control group. However, isuprel infusion resulted in significant rise of FFA compared to its initial value. In conclusion this study has demonstrated that prostaglandins may be partially involved in the hypersensitivity of B-receptors occurring in normal rats after withdrawal of chronic atenolol treatment

Antiepileptic drugs and oral contraceptives

The present work was conducted to investigate the effect of some of the popular antiepileptic drugs on the efficacy of oral contraceptive pins containing D-norgestrel 0.15 mg and ethinyl oestradiol 0.03 mg in adult female non-pregnant rats. Oral treatment started while the animals were in the oestrus stage of their cycle. Drugs were administered orally for twelve successive days. Half the animals in each group was isolated and the other half was kept with males during the period of treatment. The oral contraceptive used caused a significant increase in both estrogen and progesterone levels compared to the control group. No pregnancies occurred in female rats kept with males during the period of treatment in this group. The simultaneous administration of the oral contraceptive with clonazepam [12.5 mg/kg/day] caused insignificant change in the level of estrogen and progesterone compared to the contraceptive group. No pregnancies occurred in this group. While the concurrent administration of the oral contraceptive with sodium valproate [150 mg/kg/day] resulted in a significant decrease in the levels of both estrogen and progesterone compared to the contraceptive group and insignificant change compared to the control group. Seventy percent of the female rats kept with males in this group became pregnant. On the other hand, the combination of this oral contraceptive with sulthiame [50 mg/kg/day] caused no change in the level of estrogen while progesterone level was significantly decreased compared to the contraceptive group reaching a level nearly that of the control group. No pregnancies occurred in this group. In conclusion we would emphasize that sodium valproate caused failure of the oral contraceptive used in this study. The same cannot necessarily be assumed for other contraceptive drugs. Even though we feel that patients under antiepileptic drugs should be advised as a precaution to use other contraceptive methods in addition to the oral contraceptives

Effect of a calcium channel blocker [nifedipine], a beta blocker [oxprenolol] and their combination on the cardiovascular system

Twenty-four adult male dogs were used for the determination of the effects of the nifedipine, oxprenolol and their combination on arterial blood pressure [BP], electrocardiographic changes [ECG], serum lipids free fatty acids [FFA], triglycerides, total cholesterol and lasting blood glucose levels. Nifedipine produced significant increase in heart rate [HR] with inverted T wave, FFA, triglycerides and fasting blood glucose levels. Administration of oxprenolol alone produced significant decrease in BP, HR with biphasic T wave, serum FFA, triglycerides, total cholesterol and fasting blood glucose levels. The effect of combined administration of both nifedipine and oxprenolol resulted in a significant decrease in BP and a nonsignificant change in serum FFA, triglycerides, total cholesterol and fasting blood glucose levels. No changes were recorded in the ECG tracings. The results were discussed

Effect of prolonged administration of gliclazide on the thyroid function in rabbits

Gliclazide [Diamicron] is an oral hypoglycemic drug which belongs to the sulphonylurea compounds. Gliclazide was administered orally to male rabbits in a dose of 200 micro g/Kg/day. The drug was suspended in gum acacia mucilage [1%] in a concentration of 200 micro g/ml. Each of the control rabbits received 1.0 ml gum acacia mucilage [1%] orally. Treatment was performed daily for four weeks, then blood was collected for the determination of the levels of thyroid stimulating hormone [TSH], triiodothyronine [T[3]] and thyroxine [T[4]]. Treatment with gliclazide resulted in a significant decrease in the levels of TSH and T[3] and a non significant decrease in T[4]. Possible mechanisms underlying this antithyroid effect of gliclazide are then discussed