I received my M.D. degree in pharmacology from Albert Ludwigs University Medical School in Freiburg, Germany, in 1980. Parallel with medical school, I had started my thesis work in pharmacology in 1976. At that time, I was looking for a yet-unknown cyclooxygenase product of arachidonic acid that relaxed vascular tissue and the splenic capsule. This material turned out to be the potent vasodilator prostaglandin prostacyclin that was identified in 1976 by John Vane's laboratory at the Wellcome Research Laboratories in Beckenham/Kent, U.K. While continuing my work on the synthesis and metabolism of prostaglandins in various organs, I came across the paper: Furchgott and Zawadzki, Nature 288, 373-376, 1980, that reported on a non-prostaglandin vasodilator that they termed endothelium-derived relaxing factor (EDRF). I started to work on the properties of this factor. By the mid-80s, we knew that EDRF was short-lived (Förstermann et al., Eur. J. Pharmacol. 106, 639-643, 1984) and that the factor produced its vasodilator effects by acting directly on soluble guanylyl cyclase (Förstermann et al., Circ. Res. 58, 531-538, 1986).

With regard to the chemical nature of EDRF we initially followed an erroneous path. Pharmacological evidence generated with inhibitors of lipoxygenases, epoxygenases, and acyl-coenzyme a:lysolecithin acyltransferase and with stimulators of phospholipase A2 were suggestive of EDRF being a peroxy-derivative of arachidonic acid, which later turned out not to be the case.

Following the identification of EDRF as nitric oxide (NO), my interest switched to the characterization and identification of the enzymes involved in NO synthesis. In the early ‘90s, it became clear that NO synthase existed in a constitutive calcium-regulated and in an inducible calcium-insensitive form. Then, in 1991, we were able to demonstrate that there were two constitutive isoforms of NO synthase, one predominantly expressed in neuronal cells and another mainly present in endothelial cells. This work is summarized in the 1991 article, Förstermann et al., Biochem. Pharmacol. 42, 1849-1857.

  What role did practical support (facilities, funding, etc.) play?

The research on the endothelial NO synthase was done in the laboratory of Ferid Murad (Nobel Laureate in Physiology/Medicine in 1998) at Abbott Laboratories, Abbott Park, IL. In the late ‘80s and early ‘90s, Abbott Laboratories supported NO research significantly. For example, it proved to be very difficult to purify endothelial NO synthase from animal tissues. Therefore, we started expensive roller bottle cultures of endothelial cells in order to obtain the starting for our endothelial NO synthase purification.

It is now established that endothelial NO synthase exerts important protective functions in the vasculature. These include blood-pressure reduction, as well as anti-thrombotic and anti-atherosclerotic effects. In pathophysiology, the function of the enzyme is often impaired and/or its expression can be downregulated. Both pharmacological and gene therapy approaches are taken to maintain or improve endothelial NO production under pathophysiological conditions. Although still in an experimental stage, these interventions may prove useful to mitigate atherosclerosis and improve vascular function in diseases such as diabetes, hypercholesterolemia, hypertension, etc.

  What would you rate as your most difficult or trying professional moment?

In 1991, in the midst of a very successful and productive phase of research at Abbott Laboratories, our mentor Ferid Murad suddenly left the company. At that time, it was not clear what was going to happen to the group of almost 20 scientists from eight different countries doing basic research. Fortunately, after a period of uncertainty, many of us, including myself, found decent positions in academia all over the world.

  Which of your professional achievements brings you the most satisfaction?

I enjoy doing basic research, but always with a potential clinical application in mind. In that respect I cannot and will not deny my medical background. I like stimulating scientific discussions with colleagues. I also enjoy seeing young students generate their own ideas, apply new techniques, and develop into independent scientists.

  Aside from your scientific career, what is your greatest or most compelling ambition in life?

To teach my children to become decent and ethical human beings. To see more of the world and achieve a better understanding of other cultures.

Professor Ulrich Förstermann, M.D., Ph.D.
Johannes Gutenberg University
Department of Pharmacology
Mainz, Germany