Researchers at the University of Nottingham Medical School (UK) are studying the effects of endocannabinoids on circulation. These substances produced by the body bind to the same receptors as cannabinoids of the hemp plant. The prototypic encocannabinoid anandamide (N-arachidonylethanolamide) derived from arachidonic acid, has been shown to be a vasorelaxant, particularly in the resistance vasculature (arteries), which can reduce blood pressure.

The study is being funded with a 120,000 pounds grant from the British Heart Foundation. Dr. David Kendall, one of the scientists, said: "This research should tell us a great deal more about how these substances affect our circulation.This is a new and exciting area of research which could ultimately lead to better treatments for a range of cardiovascular diseases."

Professor Brian Pentecost, medical director of the British Heart Foundation, said: "These are natural substances, present in all our bodies, that seem to have important effects on our circulation. Hopefully this project will shed new light on how we could use these effects to help heart patients."

High blood pressure, or hypertension, affects between 10 and 20 percent of adults in western societies. Hypertension puts a strain on the heart and blood vessels and greatly increases the risk of stroke and heart disease.

The activation of Kalium channels seems to play a role in the vasorelaxation caused by anandamide. Dr. Michael Randall and Dr. David Kendall from Nottingham propose that an endocannabinoid may mediate the nitric oxide- and prostanoid-independent component of endothelium-dependent relaxations. It has recently been shown that anandamide is produced by endothelial cells. (Endothelial cells cover the the inner walls of blood vessels. Nitric oxide and prostaglandins play a major role in endothelium-dependent relaxation but do not explain all effects.)

This hypothesis has generated some scientific controversy. It is unclear wether the effect on blood vessels is cannabinoid receptor dependent (Randall 1997) or cannabinoid receptor independent (Plane 1997). A research group of the Medical College of Wisconsin in Milwaukee suggests that the vasodilatory effect of anandamide results from its metabolism to arachidonic acid followed by enzymatic conversion to vasodilatory eicosanoids such as prostaglandins (Pratt et al. 1998).

Further observations concerning the role of endocannabinoids in vasorelaxation from other research groups:

Activation of peripheral CB1 cannabinoid receptors contributes to hemorrhagic hypotension in septic shock. They seem to be activated by anandamide derived from makrophages as well as by platelet-derived 2-arachidonyl glyceride (another endocannbinoid) (Varga 1998).

An anandamide signaling system is present in the kidney, where it exerts significant vasorelaxant and neuromodulatory effects. The CB1 receptor and the CB2 receptor is found. The vasorelaxation is blocked by a CB1 cannabinoid receptor antagonist (Deutsch 1997).

(Sources: PA News of 29 December 1998; Randall MD, Kendall DA: Eur J Pharmacol (1998) 346:51-53; Randall MD, Kendall DA: Trends Pharmacol Sci (1998) 19:55-58; Varga K, et al: FASEB J (1998) 12:1035-1044; Deutsch DG, et al.: J Clin Invest (1997) 100:1538-1546; Plane F, et al: Br J Pharmacol (1997) 121:1509-1511; Pratt PF, et al: Am J Physiol (1998) 274:H375-381; Randall MD, et al: Eur J Pharmacol (1997) 333:191-197)