Press Release
Nitric Oxide, an Unexpected Ally for the Heart
In Naples, the ‘Hydrogen Sulphide and Nitric Oxide in Health and Disease’ Symposium
Nitric oxide is the mediator on which the actions of many medicinal products used in cardiovascular medicine are based.
The effects of nitric oxide on the circulatory system have been exploited to develop medicinal products used to combat erectile dysfunction.
Researchers in Naples have identified similar characteristics in hydrogen sulphide.
In the future, using nitrogen oxide, it may be possible to develop medicinal products to fight hypertension, arteriosclerosis, stroke, angina pectoris, heart failure, the vascular complications of diabetes, and gastrointestinal ulcer.
Naples, 19 May 2014 – Little known substances, or substances considered harmful – such as certain gases and oxides – are instead the bases for medicinal products which act against cardiovascular diseases – as is the case of nitroglycerine – or as vasodilators, as in medicinal products for combating erectile dysfunction. This is the case of nitric oxide and hydrogen sulphide, the two substances under scrutiny at the symposium on ‘Hydrogen Sulphide and Nitric Oxide in Health and Disease’ organised in Naples by the School of Pharmacy of the Università di Napoli Federico II and promoted by the Fondazione Internazionale Menarini (Menarini International Foundation).
A little over thirty years ago, Luis Ignarro, a U.S. biochemist (now with the University of California, Los Angeles – UCLA), discovered that nitric oxide acts as an intracellular mediator in the human body. Ignarro, whose father was from Torre del Greco, as awarded the 1998 Nobel Prize in Medicine for his discovery. Today, the researcher is in Naples to share information on progress and results to date with his Italian and international colleagues. Clinical studies are investigating cardiovascular diseases in particular. ’Nitric oxide and hydrogen sulphide are involved in many cardiovascular diseases, since altered secretion (over-secretion and under-secretion alike) can have pathological or beneficial effects,’ explains Giuseppe Cirino, Professor of Pharmacology at the Università di Napoli Federico II and Symposium chairman. ‘In particular, nitric oxide is the mediator on which the actions of many medicinal products used in cardiovascular medicine is based. The best-known are probably the nitro derivatives such as nitroglycerine, which are widely used.’
Nitric oxide has other potential applications outside of cardiovascular medicine. ‘This substance also shows significant activity in the gastrointestinal, genitourinary, and respiratory tracts and in the brain,’ comments Ignarro. ‘Basing our work on these properties, we can develop medicinal products to combat hypertension, arteriosclerosis, stroke, angina pectoris, heart failure, the vascular complications of diabetes, and gastrointestinal ulcer. A good example in this context is nebivolol, a third-generation cardioselective beta-blocker with the capacity to release nitric oxide. Several studies, especially the study on seniors, demonstrated that nebivolol is efficacious in heart failure, reducing mortality from cardiovascular disease by 14% and sudden death by 39%. And finally, nitric oxide plays an important role in maintaining balance not only in blood vessels but also in the peripheral nervous system, where it is the principal neurotransmitter in the neurons which innervate smooth muscles and tissues, including those that regulate erectile function,’ explains Ignarro.
Synthesis of nitric oxide is stimulated by many factors, such as ‘shear stress’, a parameter that measures the force exerted by blood flow on the vessel walls. ‘When arterial blood pressure increases to an excessive degree, the body defends itself by synthesizing nitric oxide, which, by dilating the vascular walls, contributes to lowering blood pressure,’ Cirino continues. ‘Conversely, if synthesis of nitric oxide is inhibited we have an increase in peripheral vascular resistance and, consequently, an increase in arterial blood pressure.’
It was by exploiting this mechanism that researchers were able to put the effects of nitric oxide on the circulatory system to use in developing the medicinal products used to combat erectile dysfunction. And collaboration between Ignarro and the Neapolitan clinics led to identification of similar characteristics in another substance, hydrogen sulphide. Researchers at the Università Federico II of Naples have demonstrated that human corpora cavernosa contain two enzymes that transform a common amino acid present in the cells of the corpora cavernosa into hydrogen sulphide, a gaseous mediator capable of dilating the arteries which supply the corpora cavernosa, producing relaxation of the smooth musculature of the vessel walls and acting as a stimulator of the physiological mechanism of erection.
‘This discovery permitted identifying an alternative process for controlling erection, different from that mediated by nitric oxide, which is currently the best known in clinical practice and that on which the oral medicinal products currently available for treating erectile dysfunction are based,’ concludes Cirino. ‘This discovery opens the doors on a totally innovative scenario in the field of research into male impotence, since we can well imagine that medicinal products acting on this molecular mechanism may be produced in the near future.’