Nitrovasodilators

Group of drugs that are broken down in the smooth musculature of the vessels of the large and small circulation and the draining urinary and biliary tracts, thereby releasing NO (nitric oxide) (NO donors). Nitrovasodilators are basic therapeutics for coronary heart disease.

There are two groups of nitrovasodilators:

Organic nitrates (from these NO is released enzymatically). These include the nitric acid esters:

• glycerol nitrate (GTN)
• Isosorbiddinitrate (ISDN)
• Isosorbide-5-mononitrate (ISMN)

Nitroprusside sodium and molsidomine: These substances release NO non-enzymatically. In this respect, molsidomine, among others, is only effective after 20-30 minutes, as it must first be pre-systemically metabolized in the liver (see Metabolic pathway of molsidomine).

• Nitroprusside sodium is an unstable, light-sensitive complex compound that decomposes on contact with cell membranes to form NO.
• In the liver,molsidomine is first metabolized to linisidomine and then to the unstable sydnonimine. Sydnonimine decomposes spontaneously with release of nitric oxide.

From today's point of view, endothelia contribute to the regional modulation of vascular blood flow in the coronary bed by autocrine and paracrine functions. Since 1987 it is known that the endothelium releases nitric oxide (NO). This (endogenous) NO production can be stimulated by various stimuli, e.g. bradykinin, substance P, ATP, thrombin, and serotonin.

Anti-aggregatory effect of NO: As a lipophilic gas, NO can diffuse very rapidly towards the lumen of the vessel and reach the platelets. After prostacyclin, NO is the strongest antiaggregatory agent for platelet adhesion and aggregation.

Muscle relaxant effect of NO: NO can induce relaxation in the smooth muscle cell. The released NO activates the cytoplasmic soluble guanylate cyclase (GCs) in the smooth muscle cells. This leads to the formation of cGMP, which relaxes smooth muscle cells. There are many indications that the interaction between thrombocytes, endothelia and smooth muscle cells is disturbed in the context of CHD. The increased platelet aggregation leads to the release of substances such as serotonin, histamine and thrombin, which can then lead to corresponding reactions in the endothelium or smooth muscle cell.

Anti-ischemic effect of nitrovasodilators: All therapeutically applied nitrovasodilators develop their anti-ischemic effect uniformly through the same mechanism. They release radical NO, albeit via different bioactivation pathways. NO has the greatest relaxation effect where there is the greatest lack of physiological (endogenous) NO. Coronary angiographic studies in humans have also confirmed that coronary vessel segments that are arteriosclerotically altered react particularly strongly to radical NO.

Improvement of myocardial function and increase of oxygen supply for poorly perfused parts of the myocardium.

Nitrovasodilators have a similar spectrum of side effects, although to different degrees:

• Nitrate headache
• Orthostatic dysregulation (= orthostatic hypotension)
• Nitrate Syncopes
• Tolerance development
• Rare are allergic skin reactions and contact dermatitis with local application

Interactions: Nitrovasodilators weaken the effect of heparin! The antihypertensive effect is enhanced by alcohol, neuroleptics or tricyclic antidepressants.

1. Graefe KH et al. pharmaceuticals with effects on the vascular system. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S.177-181