Dihydropyridines, Nitric Oxide and Vascular Protection

Abstract

For more than decades calcium antagonists (CEBs) have been widely used for the treatment of myocardial ischaemia (angina pectoris). Among the classes of CEBs, the 1,4-dihidropyridine (DHPs) have been used for this indication because of their haemodynamic and electrophysiological properties. In particular, DHPs are compounds capable of vascular protection on both smooth muscle and endothelium. The main protective activity is related to their calcium antagonist activity. In addition, they present vascular dilatation function, which has been related to an anti-endothelin efficacy. The newer DHPs are endowed with slow onset and long duration of vasodilator activity and reduce coronary resistance with little or no effect on heart rate. The more lipophilic DHP, lacidipine, is also able to reduce the formation of atheroma plaque in animal models at therapeutic doses. It has potent and long-lasting antihypertensive properties and appears to protect the arterial wall against the development of atherosclerotic lesions in animal models or human subjects with severe and multiple risk factors. Additionally, it has been observed that: i) NO/cyclic GMP pathway facilitates the inhibitory effect of Ca(++) antagonists on KCl-evoked contraction in rat aorta; ii) Vasodilator effect of lacidipine was significantly attenuated in the presence of NO-synthase inhibitors; iii) DHPs stimulate an electrochemical activity related to the nitric oxide (NO) system within the aortic vessel tissue, in rats and mice. In particular, they implement endothelial NO at "useful" and not toxic nanomolar levels. These activities join the already described positive effects of these compounds upon vascular functions.

Influence of nicotine upon human brain metabolism, an in vivo noninvasive Near Infrared Spectroscopy (NIRS) study

“…Indeed, Uchida and Hotta have reported enhanced cerebral flow in the cortex of anesthetized rats treated with nicotine [29]. Such effect has been related to the capability of nicotine to activate the nitric oxide system that is indeed inducing vasodilatation in brain [30] following activation of nicotinic receptors [29,31].…”

Respuesta inflamatoria y cirugía protésica. Su control con donadores de óxido nítrico

“…Mucho se ha investigado sobre el papel que podría jugar el NO en el fenómeno inflamatorio y en concreto en los procesos secundarios a isquemiareperfusión, otorgándole últimamente un efecto protector (39,57,121,180,186,187,188,220,248,198,117,23,221,242,293,269,288) , si bien, el balance final de su actividad, los diferentes caminos en los que se encuentra implicado, y los oscuros efectos que pudiese ejercer aún no están completamente dilucidados y conducen a la controversia ( 59,164,165,289,135,221,304,226,139) .…”

“…El óxido nítrico, una pequeña molécula radical libre gaseosa, es un importante mensajero de la función celular y biológica que demuestra un interesante perfil antiinflamatorio y una actividad vascular protectora (23) . Pero Entre los efectos beneficiosos parecen demostrados los siguientes (2,15,39,53,57,58,60,98,94,96,121,141,173,180,186,187,188,220,245,248,258,198,117,23,221,242,293,269,288 ) (ver también Tabla I):…”