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

Abstract

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.

The role of endothelin receptor antagonism in collar-induced intimal thickening and vascular reactivity changes in rabbits

“…Morover, Geerts et al (2000) further reported that collar placement elevates mRNA expression and activity of the 5HT 1B receptor in the rabbit carotid artery. In our study, consistent with previous results (De Meyer et al 1994;Ü stu¨nes et al 1996;Kerry et al 1999;Yasa et al 1999), the collar placement suppressed 120 mM KCl-induced contractions in collared rabbit carotid arteries. In the collar model, attenuation of KCl-induced contractions is well known and has been discussed in detail (Kockx et al 1992;De Meyer et al 1994).…”

“…In accordance with the findings of previous studies (Ü stu¨nes et al 1996; Kerry et al 1999), collaring increased the pD 2 values of 5-HT in arteries, a characteristic feature of the collar model (De Meyer et al 1990Hickey et al 1996). As stated before, the 5-HT 1B receptor subtype has been found to be responsible for the development of hypersensitivity to 5-HT in the collar model (Geerts et al 1999(Geerts et al , 2000.…”

“…One of these experimental models, in which intimal thickening was induced by placing a collar around the rabbit carotid artery, was used in this study (Booth et al 1989). In this model, independently of formation of intimal thickening, it has been reported that changes in the functional characteristics of collared arteries to vasoconstrictor agents have occurred (Soma et al 1994;Van Put et al 1995;Kerry et al 1999). Among these, hypersensitivity to serotonin (5-hydroxytryptamine, 5-HT) is the most pronounced (De Meyer et al 1990.…”

Lacidipine has antiatherosclerotic effects independent of its actions on lipid metabolism and blood pressure

“…On the other hand NTG-induced vasorelaxation was not changed neither by collar (Fig. 5)- correlated with previous studies- (De Meyer et al, 1992, Kerry et al, 1999, Verbeuren et al, 1986, Yasa et al, 1999) nor by lacidipine. Based on these data we suggest that increased vasorelaxation to ACh by lacidipine was due to enhanced production of NO.…”

Collar‐induced elevation of mRNA and functional activity of 5‐HT1B receptor in the rabbit carotid artery

“…A similar hyperreactivity to 5‐HT develops when the rabbit carotid artery is surrounded by a flexible, silicone collar to induce intimal thickening ( De Meyer et al ., 1994 ) which is an essential prerequisite for the development of atherosclerosis in human arteries ( Stary et al ., 1995 ). Nevertheless the hypersensitivity to 5‐HT and the intimal hyperplasia are separate responses to the damage of the media ( De Meyer et al ., 1997 ) evoked by the collar ( De Meyer et al ., 1990 ; Kerry et al ., 1999 ; Van Put et al ., 1995 ; Üstünes et al ., 1996 ). According to clinical observations the concentration of platelet released products, including the vasoconstrictor agents 5‐HT and thromboxane A 2 (TXA 2 ), are significantly elevated in patients suffering from vasospasm ( van den Berg et al ., 1989 ; Vikenes et al ., 1999 ).…”