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Sir James Black, President

High Blood Pressure Foundation 15th Annual Report 2005

A Message from the President of the High Blood Pressure Foundation, Sir James Black, FRS, FRSE, 2005

President's message

A few weeks ago, I came across a paper in a pharmacology journal with the heavy title, ‘Evolving the concept of regulation of vascular tone in humans’. The regulation of vascular tone, or the degree of constriction of small blood vessels, determines the resistance to the flow of blood ejected from the heart with each heart beat. The greater the resistance, the higher the blood pressure in the large blood vessels. So, this paper was claiming to go to the ‘heart’ of the problem of high blood pressure. And the claim was that anandamide plays a significant role in the regulation of vascular tone in man. Anandamide! Where had I met this molecule before? So, I looked up anandamide in Google and got more than I bargained for!

Anandamide is a naturally-occurring ‘messenger molecule’. Messenger molecules act on ‘receptors’ on the surface of nerve cells. Receptors decode the information carried by messenger molecules and pass the instructions into the chemical machinery inside the cell. And what are the receptors that anandamide acts on? Bliss receptors! Anandamide is known to produce sensations that are similar to those of THC, tetrahydrocannibol, the psychoactive ingredient of cannabis, marijuana and hemp. Put the other way round, the THC in cannabis produces its psychoactive effects by acting on anandamide’s naturally-occurring ‘bliss’ receptors. We now know that there are strong chemical similarities between THC and anandamide such that anandamide is now classified as a cannabinoid.

Darwinian evolution teaches us that plants diverged from animals about 500 million years ago. And yet here is a plant, cannabis, that produces a chemical for its own needs that precisely mimics an important messenger molecule produced by animals for their own quite different needs. This could be just a biological fluke were it not for the fact that there are many similar examples of chemicals synthesised by plants for their needs that mimic chemically-distinct chemicals produced by animals for their quite different needs. Many of these plant molecules interfere with the activity of animal messenger molecules, with their synthesis or physiological activity or destruction. For example, morphine, synthesized by the seeds of poppies, stimulates receptors in the brain that are normally activated by small, protein-like, molecules that we now know of as encephalins. Atropine, synthesized by the leaves of the belladonna plant, blocks the receptors for acetylcholine in tissues in the gut, blood vessels and other organs. On the other hand, nicotine, produced by the tobacco plant, acts on acetylcholine receptors on nerve cells in brain and other tissues. Curare, the South America arrow poison derived from a species of strychnos plant, paralyses skeletal; muscles by blocking the receptors for the acetylcholine released by the motor nerves. And so on for many other plant products. Invariably, the effects in man of plant products preceded by many years, centuries, our understanding of how their specific effects were being produced. Indeed, their existences were often vital tools in understanding human and animal physiology. Intelligent design?!

Back to anandamide. Anandamide was discovered by analysing the effects of cannabis-derived THC on brain tissues. However, receptors for anandamide have now been discovered in the peripheral nerves associated with blood vessels. Activation of anandamide receptors strongly dilates blood vessels. The important physiological point is that anandamide seems to have a managerial role in controlling the activity of a number of already- known vasodilator pathways. The question raised by the paper I started from is whether anandamide could provide a blueprint for devising new drugs for treating high blood pressure. We now know that the control of blood pressure involves a large number of chemical components that are integrated into a ‘system’, such that the whole is greater than the sum of the individual parts. So when the blood pressure control system falls out of kilter to produce the ‘high blood pressure’ syndrome, no one chemical component will be to blame. When we don’t know what components are out of control in a particular patient, the physician has to try, with drugs, to modify as many as possible. That is why doctors treat high blood pressure with a package of beta-blockers, angiotensin antagonists and diuretics. Could new drugs related to anandamide make a significant contribution to a doctors’ armoury? I do not know but I believe that scientific progress is all about getting and exploiting new ideas.

This review offers ‘one for the road’!

Sir James Black