Asli Özer

Effect of verapamil on intimal thickening and vascular reactivity in the collared carotid artery of the rabbit.

1 . Intimal thickening is a common site for atherosclerosis. Therefore, we investigated whether the calcium entry blocker verapamil (10 mg kg−1 body weight day−1, s.c.) can retard intimal thickening and changes in vascular reactivity induced by a non‐occlusive, silicone collar positioned around the left carotid artery of rabbits. The contralateral carotid artery was sham‐operated and served as a control. 2 . Verapamil and placebo (saline 0.1 ml kg−1 day−1, s.c.) treatments were initiated 7 days before placing the collar and lasted 3 weeks. Thereafter, segments were cut from collared and sham‐treated arteries for histology and isometric tension recording. 3 . The intima/media (I/M) ratio increased after 14 days of collar treatment, but intimal thickening was not inhibited by verapamil (I/M ratio placebo 0.31 ± 0.07, verapamil 0.32 ± 0.09). 4 . The collar decreased the capacity to develop force, as indicated by the response to a supramaximal concentration of KC1, decreased the sensitivity (pD2) to acetylcholine (ACh) and phenylephrine (Phe), but increased the sensitivity to 5‐hydroxytryptamine (5‐HT). 5 . Although verapamil did not affect intimal thickening, it normalized the hypersensitivity to 5‐HT in collared arteries. 6 . The contraction to the supramaximal concentration of KC1 was not affected by verapamil. Verapamil decreased the Emax of ACh, but this was only seen in collar‐treated arteries. Verapamil also decreased the sensitivity to ACh and Phe, in both sham‐ and collar‐treated arteries. 7 . We conclude that verapamil, without preventing thickening of the intima, can modify collar‐induced changes in vascular reactivity.

Isolation and identification of two isomeric trihydroxy octadecenoic acids with prostaglandin E-like activity from onion bulbs (Allium cepa).

Two fractions with prostaglandin E-like activity were isolated from onion (Allium cepa) by using XAD-2 adsorption, silicic acid column chromatography and thin layer chromatography. The fractions were analyzed by gas chromatography/mass spectrometry and were characterized as isomeric mixtures of 9,10,13-trihydroxy-11-octadecenoic and 9,12,13-trihydroxy-10-octadecenoic acid, which are lipoxygenase metabolites of linoleic acid. Bio-assay, for which cascade superfusion was used and the rabbit coeliac and mesenteric arteries and the rat fundus strip were employed as assay organs, was utilized to monitor the bio-active profile throughout the isolation procedures. The activity of 1 microgram of the pharmacologically active fractions T1 and T2 was found to be equivalent to that of respectively 1.33 and 0.63 ng of prostaglandin E2.

Effects of Nicardipine on Collar-induced Intimal Thickening and Vascular Reactivity in the Rabbit

The effects of nicardipine treatment on collar‐induced intimal thickening and on accompanying reactivity changes in rabbit carotid artery have been investigated.

Effects of treatment with FK409, a nitric oxide donor, on collar-induced intimal thickening and vascular reactivity.

Intimal thickening in arteries is considered a site of predilection for atherosclerosis. In a rabbit model of early atherosclerosis, a silastic collar was placed around the carotid artery, which resulted in the formation of intimal thickening. We investigated whether the oral application of FK409 ((+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide , 10 mg kg(-1) day(-1), p.o.), a nitric oxide donor, inhibited the collar-induced intimal thickening as well as accompanying reactivity changes in rabbit carotid artery. The intimal thickening was significantly inhibited by FK409. The collar treatment increased the pD2 value of 5-hydroxytryptamine (5-HT) whereas it decreased those of phenylephrine and acetylcholine and did not significantly alter that of nitroglycerine. Maximal contractile force development in response to potassium chloride (KCl), 5-HT and phenylephrine was decreased in collared arteries. The collar did not alter the maximal relaxant effects of acetylcholine and nitroglycerine. Despite the significant reduction of intimal thickening, FK409 treatment did not affect these collar-induced modifications in vascular reactivity.

The Effects of Calcium Channel Blockers are not Related to their Chemical Structure in the Collar Model of the Rabbit

Placing a silicone collar around the rabbit carotid artery induces intimal thickening, an early stage in atherosclerosis and restenosis. We investigated whether treatment with oral pranidipine, a new potent, long-lasting dihydropyridine calcium channel blocker (CCB), inhibited collar-induced intimal thickening in addition to the changes in vascular reactivity usually observed in this model. Pranidipine treatment did not inhibit collar-induced intimal thickening. Placing the collar around the carotid artery resulted in the characteristic changes in vascular reactivity, such as increased sensitivity to 5-hydroxytryptamine. Treatment with Nω-nitro-l-arginine (100 μM) and pranidipine, however, did not affect collar-induced changes in vascular reactivity. From results of this and previous studies, we conclude that pranidipine does not prevent collar-induced intimal thickening or collar-induced changes in vascular reactivity. Not all CCBs prevent collar-induced intimal thickening, suggesting that the effects of these agents are not related to their chemical structure and/or their calcium channel-blocking actions.

Diverse effects of calcium channel blockers in the collar model.

Objective — Calcium channel blockers (CCBs) are among the most frequently prescribed cardiovascular drugs. It has been shown that these drugs have antiatherosclerotic effects in both experimental and clinical settings. However, calcium channel blockers have markedly different chemical structures and different effects on the cardiovascular system.We investigated the effect of CD-832, a Ca+2 channel antagonist, on collar-induced intimal thickening, as well as accompanied reactivity changes in rabbit carotid artery. Methods and results — Rabbits received 5 mg/kg/day CD-832 or vehicle (polyethylene glycol, 0.5 ml/kg/day) intramuscularly for a week before and 2 weeks after the collar application. Histological and isometric force measurements were performed in segments from sham and collared carotid arteries. A three-week treatment with CD-832 did not inhibit the intimal thickening caused by perivascular application of a silicone collar. Potassium chloride (KCl), phenylephrine, 5-hydroxytryptamine (5-HT, serotonin) and histamine induced concentration-dependent contractions in both sham-operated (sham) and collared arteries. Collar-induced attenuations in maximum KCl, histamine, phenylephrine and 5-HT contractions were not affected by CD-832. Collaring caused an increase in pD2 values of 5-HT and a decrease in those of phenylephrine, histamine and acetylcholine. CD-832 did not affect the altered sensitivity to these agonists. Conclusions — These results demonstrate that, in rabbit carotid artery, CD-832 did not inhibit the collar-induced intimal thickening and did not affect the accompanying changes in vascular reactivity

Sustained-release dosage form of nitrofurantoin. Part 2. In vivo urinary excretion in man

The in vivo absorption of crystalline nitrofurantoin and the dosage forms of nitrofurantoin prepared with microcapsules were carried out in man by determination of urinary excretion of unchanged nitrofurantoin. The cumulative amount of drug excreted and the duration of the therapeutic urine levels were compared. The microcapsule administration showed that the peak reached during the excretion of nitrofurantoin in urine, decreased significantly when compared to the pure drug. This could be an explanation for the decrease in side-effects of nitrofurantoin such as nausea and vomiting. Experiments in male albino rats showed that the microcapsules did not produce gastric haemorrhage seen with the same doses of the pure drug.

The effect of a single treatment with cigarette smoke on the blood levels and hemodynamic effects of propranolol in rats

SummaryThe effect of a single treatment with cigarette smoke on the blood levels and hemodynamic effects of propranolol in rats was studied. Pentobarbital sleep time was not affected whereas zoxazolamine paralysis time was shortened 72% in rats, 24 h after the cigarette smoke exposure. The gb-adrenoceptor blocking effect of propranolol observed at 10 and 20 min time intervals was abolished in rats exposed to cigarette smoke 24 h after the exposure. The blood propranolol concentrations were decreased in rats pretreated with phénobarbital, 3,4-benzpyrene and ethanol as well as in cigarette smoke exposed rats. Among several factors that could influence propranolol metabolism, in this study, enzyme induction is suggested to be dominant.

The effect of cigarette smoke on the plasma piroxicam concentrations in rats

Abstract— The plasma concentration of unchanged piroxicam has been determined at 15, 30, 60 and 90 min after 10 mg kg−1 oral administration of the drug to rats exposed to cigarette smoke or pretreated with phenobarbitone, 3,4‐benzpyrene or ethanol. Plasma piroxicam concentrations decreased in rats pretreated with phenobarbitone, 3,4‐benzpyrene and ethanol and in rats 24 h after exposure to cigarette smoke.

Contraction induced by (-)-tartaric acid on rat isolated gastric fundus and its inhibition with indomethacin

Tartaric acid‐evoked contractions of the rat isolated fundus could not be antagonized by atropine sulphate or methysergide hydrogen maleate, but were partially reduced by mepyramine hydrochloride. The contractions were prevented by indomethacin (25 μ ml−1) although the tissue remained sensitive to PGE2.