Vasoconstrictor responses after neo‐intima formation and endothelial removal in the rabbit carotid artery

Abstract

1 The present study examined the responses of the rabbit carotid artery to five vasoconstrictors after neo-intima formation induced by perivascular collar treatment and evaluated the role of constitutive and inducible nitric oxide (NO) synthase and endothelial cells (ECs). 2 Ring segments of the rabbit carotid artery were mounted in organ chambers for isometric tension recording. Neo-intima-bearing vessels developed less force (Em,.) in response to KCl, the thromboxanemimetic U-46619 and 5-hydroxytryptamine (5-HT), but not to angiotensin I and II. 3 The collar-treatment increased the sensitivity to 5-HT, and decreased the sensitivity to angiotensin II. The sensitivity to U-46619 and angiotensin I remained unchanged. 4 Mechanical removal of ECs and inhibition of NO biosynthesis by N0-monomethyl-L-arginine (L-NMMA) and N0-nitro-L-arginine (L-NOARG) increased the sensitivity to 5-HT in sham and collartreated segments to the same extent. The effects of collar-treatment and endothelial removal or treatment with inhibitors of NO biosynthesis were additive. Inhibition of NO biosynthesis failed to augment sensitivity to 5-HT after endothelial denudation. L-NOARG increased the force development to KC1 in sham and collar-treated segments to the same extent. However, L-NMMA and L-NOARG failed to augment the contractile responses of neo-intima-bearing vessels to 5-HT and KCl after endothelial removal. 5 The responses to angiotensin I were not altered, either by the neo-intima or by endothelial removal. In arteries with a neo-intima the sensitivity to angiotensin II was decreased. Removal of the endothelium or incubation with L-NOARG counteracted this rightward shift and increased Em|. 6 Our results demonstrate that contractions to 5-HT, angiotensin II and KCl are modulated by NO in both sham and neo-intima-bearing vessels. Inhibition of NO biosynthesis and collar treatment resulted in additive effects on the EC50 values, suggesting that the 5-HT and angiotension (AT) receptors on the smooth muscle cells are also modified by the formation of a neo-intima. Furthermore, the reduced contractile responses of segments with a neo-intima are not due to NO formed by an inducible NO synthase in those vessels.

Periadventitial Inducible Nitric Oxide Synthase Expression and Intimal Thickening

“…10 Furthermore, in that study, it had also been reported that carotid arteries that had been collared for 7 days, but not control arteries, produced an increase in resting tone after addition of N G -nitro-L-arginine (10 Ϫ5 mol/L), suggesting a higher basal release of NO in collared arterial segments than in controls. 13 This confirmed our previous study, 25 which demonstrated that N G -nitro-L-arginine (2ϫ10 Ϫ5 mol/L) increased the contraction to KCl in collared arteries. However, this effect was seen only when ECs were present.…”

“…However, this effect was seen only when ECs were present. 25 The discrepancy between these 2 studies may be explained not only by the absence or presence of ECs but also by the differences in the presence of remnants of periadventitial granulation tissue on the ring segments in the organ chambers.…”

Role of p42/p44 mitogen-activated-protein kinase and p21 waf1/cip1 in the regulation of vascular smooth muscle cell proliferation by nitric oxide

“…Increased VSMC proliferation has been attributed to dysfunction of or damage to the endothelial lining in the area of intimal thickening and, more specifically, to decreased nitric oxide (NO) production. This effect is made evident by several studies in which NO donor agents or NO synthase gene transfer were shown to inhibit neointimal formation after balloon angioplasty in animal models (2)(3)(4). The effect inverse has been shown in studies where animals were subjected to balloon angioplasty and then treated with inhibitors of NO synthase (4).…”

Investigation of changes in vWF expression in rabbit carotid artery collar model

“…Yaka modelinin en karakteristik özelliklerinden biri de vasküler kasılma ve endotelyuma bağlı gevşe-me yanıtlarında meydana gelen değişikliklerdir (9,25) . Modelde endotelyum fiziksel bütünlüğünü koruması-na rağmen erken aşamada belirgin endotelyal disfonksiyon mevcuttur (9,26,27) .…”