Dihydropyridines, Nitric Oxide and Vascular Protection

Author: Crespi, Francesco

Source: Current Vascular Pharmacology, Volume 3, Number 2, April 2005 , pp. 195-205(11)

Publisher: Bentham Science Publishers

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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.

Keywords: dihydropyridines; nitric oxide; voltammetry; rat aortic rings

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1570161053586949

Affiliations: 1: Biology, Psychiatry CEDD, GlaxoSmithKline, via Flemming 4, 37135, Verona, Italy.

Publication date: 2005-04-01

More about this publication?

Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.

Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.

Debates will also be encouraged in the correspondence section of this journal.

Dihydropyridines, Nitric Oxide and Vascular Protection

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