Ulster says 'NO'; explosion, resistance and tolerance. Nitric oxide and the actions of organic nitrates.

Those who have started to read this review expecting a discussion of the political situation in Northern Ireland will either be relieved or disappointed. The title refers to the discovery and actions of nitric oxide and the role played by investigators in Northern Ireland, its relationship to the explosive nitroglycerine and the concepts of nitrate resistance and tolerance in cardiovascular medicine. In 1867 Thomas Brunton, a newly qualified house surgeon at the Edinburgh Royal Infirmary pioneered the clinical use of the sphygmomanometer by employing it to monitor the increase in blood pressure associated with episodes of angina pectoris. Brunton speculated that amyl nitrite, a drug which he had observed to lower blood pressure in animals, might be used to relieve angina pectoris. He obtained a sample of amyl nitrite and poured it on to a cloth for his patient to inhale. Within a minute the pain disappeared and the patient remained free of pain for several hours.' Along with other nitrates and nitrites Brunton investigated the compound nitroglycerine which had become widely available following Alfred Nobel's discovery ofits property as an explosive. Later the following year, William Murrell, a registrar at the Westminster Hospital decided to resolve the conflicting reports in the literature as to whether nitroglycerine caused severe headache or not. The French chemist, Ascagne Sobrero, who had first synthesised the compound, reported in 1847 that he experienced an intense headache after tasting a small drop placed on his finger. Others had similar experiences including Arthur Field, a Brighton dentist who claimed in the Medical Times and Gazette that if placed on the tongue it could alleviate toothache and neuralgia. He contended that it would be a highly effective remedy for these conditions if it were not for the severe accompanying headache. In contrast, others reported no effects whatsoever after swallowing large amounts ofnitroglycerine. Murrell suspected that the differences were largely due to variation in the susceptibility of different individuals, and decided to conduct an experiment in healthy volunteers. In the course of one of his outpatient clinics he licked the moist cork of the bottle containing nitroglycerine solution and within a few seconds began to experience a throbbing headache and a pounding in the chest. After five minutes he had recovered sufficiently to resume his clinic but the headache persisted for most of the afternoon. With further experimentation, Murrell determined three important pharmacological properties of nitroglycerine; the effect …