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 KCl, decreased the sensitivity (pD2) to acetylcholine (ACh) and phenylephrine (Phe), but increased the sensitivity to 5-hydroxytryamine (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 KCl 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.

The effects of nicardipine treatment on collar-induced intimal thickening and on accompanying reactivity changes in rabbit carotid artery have been investigated. Treatment for three weeks with subcutaneous nicardipine (20 mgkg(-1) per day) significantly inhibited the intimal thickening caused by perivascular application of a silicone rubber collar. Potassium chloride (KCl), phenylephrine and 5-hydroxytryptamine (5-HT) induced concentration-dependent contractions in both sham-operated and collared arteries. Collar-induced attenuation of maximum KCl-, phenylephrine- and 5-HT-induced contraction was not affected by nicardipine. Collaring caused the means of pD2 values (the negative logarithm of EC50 values, 50% effective concentration) of 5-HT and phenylephrine to increase and decrease, respectively. Nicardipine did not affect the altered sensitivity to these agonists. Neither collar implantation nor nicardipine treatment altered the pD2 values for acetylcholine- and nitroglycerine-induced relaxations. These results demonstrate that nicardipine inhibits collar-induced intimal thickening in rabbit carotid artery without affecting the accompanying changes in vascular reactivity, indicating a possible lack of association between the development of intimal thickening and altered reactivity.

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In rat aortic rings, methylglyoxal determines a reduction in endothelium-dependent relaxation. This effect seems to be mediated via a reduction in p-eNOS (Ser1177) and p-AMPKα (Thr172).

Magnetic iron oxide nanoparticles (IONPs) were coated with gelatin type B by means of the two-step desolvation method. Drug loading by adsorption was studied under various conditions such as different temperature, contact time, pH, and initial gemcitabine concentration. Further, Langmuir isotherm curves were constracted and constants were calculated. According to the Langmuir isotherm, the Gibbs free energy of the adsorption process at 25°C was - 4.74 kJ/mol. On the other hand, this value at 37°C was - 7.86 kJ/mol. In vitro drug release was performed at pH levels of 5 and 7.4, with gemcitabine-loaded magnetic gelatin nanoparticles and free gemcitabine, and both the results were subsequently compared.