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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1156.)
© 2009 American Heart Association, Inc.

History of Discovery

How We Learned to Say NO

Paul M. Vanhoutte

From the Department of Pharmacology and Pharmacy, University of Hong Kong.

Correspondence to P.M. Vanhoutte, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, 21 Sassoon Road, Hong Kong, China. E-mail vanhoutte.hku@hku.hk

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 

What seest thou else

In the dark backward and abysm of time

— —William Shakespeare

First, there was Robert Furchgott.¹ He simply and brilliantly demonstrated that endothelial cells play a pivotal role in relaxations evoked by acetylcholine in isolated arteries, and do so by activating muscarinic receptors of these cells. Actually, the quest for the understanding of the mechanism(s) underlying the vasodilator effect of acetylcholine in vivo (in contrast with the vasoconstrictor effect that the cholinergic transmitter almost always had in vitro) had started many years before that and led to the earlier interpretation that this could be explained best by a prejunctional (presynaptic) muscarinic effect resulting in the local inhibition of adrenergic neurotransmission in the blood vessel wall.² To be honest, I am still convinced that if acetylcholine released from cholinergic nerves (the most likely, if not the only, source of acetylcholine in our body) contributes to the control of vasomotor tone, it does so by inhibiting the release of norepinephrine in the adventitia rather than by diffusing through the media to the endothelial cells. When asked the role is of muscarinic receptors on endothelial cells, I usually respond by saying that they have been placed there to make sure that Robert Furchgott, who already had contributed immensely to pharmacology before discovering endothelium-dependent relaxations, would make the trip to Stockholm! Yet his simple pharmacological experiments had opened a totally new avenue not only in vascular pharmacology and physiology but in science in general as they set the stage for . . . [Full Text of this Article]