Therapeutic Importance of Nitrovasodilators

PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARαAgonists

“…This suggests that continued research into cardioprotective PPAR α agonists is warranted. Indeed, a class of drugs that are lipid lowering, anti-inflammatory, and that can genomically activate the NO• signaling pathway without the negative side effects of nitrovasodilators [ 56 ], as well as directly promote relaxation of vascular smooth muscle could prove very useful.…”

Inhibition of Vascular Oxidative Stress in Hypercholesterolemia by Eccentric Isosorbide Mononitrate

“…Organic nitrates are a structurally diverse group of compounds that all carry an aliphatic nitrate moiety that is enzymatically reduced by a flow of three electrons to the nitrate nitrogen to generate NO (9,10). This reduction of the nitrate moiety occurs in many cell types including vascular smooth muscle and endothelial cells, and it has been shown that treatment with organic nitrates increases the NO content of rabbit arteries and veins (11).…”

“…Although we used a high dose of ISMN, which initated nitrate tolerance even at eccentric dosing, we believe that the results of our study add another piece of evidence on potentially inhibitory effects of nitrates on the development of atherosclerosis. To achieve this effect, it is obviously important to avoid severe nitrate tolerance, as inducible with continuous nitroglycerine (30), by strictly adhering oral nitrate therapy to the recommended intermittent dosing regimen (10). Finally, a randomized placebo-controlled prospective clinical investigation is needed to elucidate the effects of organic nitrates on prognosis in the setting of human atherosclerosis.…”

Recent developments in nitric oxide donor drugs

“…The additional beneficial properties of nicorandil have been largely attributed its actions on K + channels, causing dilatation of peripheral arteries and coronary resistance vessels, reducing the afterload of the heart ( Simpson and Wellington, 2004 ; Herman and Moncada, 2005 ). This proposal is somewhat puzzling, as it is regularly argued that the reason behind organic nitrate effectiveness in the relief of angina, is their ability to selectively dilate peripheral veins over arteries ( Kojda, 2000 ), and large coronary arteries over small ( Winbury et al ., 1969 ; Kurz et al ., 1991 ). Should the dual action of nicorandil on preload and afterload be the reason for its success, it would suggest that other NO donors with more balanced arteriovenous selectivity may also be useful in the treatment of angina and ischaemic heart disease.…”