# Serafim Guimarães

Serafim Guimarães, full name Serafim Correia Pinto Guimarães, (born May 2, 1934) is a Portuguese physician and pharmacologist. With his colleague Walter Osswald (born 1928) he made the Department of Pharmacology, Medical Faculty of the University of Porto, a center of research on catecholamines and the sympathetic nervous system, especially their relation to blood vessels.

## Life

Guimarães was born in Espargo, a village close to the city of Santa Maria da Feira in the Portuguese Região Norte. He is the second son of the peasant Américo Ferreira Pinto Guimarães and his wife Maria Emília Correia née Pais. Serafim studied medicine at the University of Porto and simultaneously worked at the Department of Pharmacology. After military service in Angola from November 1963 to December 1965 he returned to the Department of Pharmacology. In 1966 he spent five months with Hans-Joachim Schümann at the University of Duisburg-Essen, in 1971 and 1977 another nine months with Ullrich Trendelenburg at the University of Würzburg. He has commemorated Ullrich Trendelenburg, who became his friend, in his book „Retratos legendados“. In 1968 he obtained his Ph.D. on the basis of his thesis Receptores Adrenérgicos – Ensaio de Interpretação e Análise (Adrenoceptors – An Attempt at Interpretation and Analysis). In 1973 he became assistant professor. He was dismissed in April 1974 in the course of the Carnation Revolution but was reinstated when the pro-Communist Coup of 25 November 1975 was defeated. In 1979 he was nominated Full Professor of Pharmacology and Toxicology. From 1990 to 2005 he was head of the Department. He retired in 2005. His successor is Patrício Soares-da-Silva (born 1957). In 1964 Serafim married Maria de Fátima née Martins de Sousa, with whom he has two sons and a daughter.

## Research

Interest in catecholamines and their receptors dominated the Porto Department in the 1960s. Work just before Guimarães' entry had suggested that there might be more than a single α-adrenoceptor, and so did one of Guimarães' first studies: forerunners of the distinction, important in the history of catecholamine research, between α$_1$- and α$_2$-adrenoceptors.
In the same year 1969 Guimarães, together with Osswald, studied the pharmacology of veins, little known as compared to arteries. All effects of the catecholamines adrenaline, noradrenaline, dopamine and isoprenaline could be accounted for by an action as agonists, activating substances, on α- und β-adrenoceptors co-existing in vascular smooth muscle. Veins and their receptors remained favourites. Guimarães has summarized the knowledge on blood vessels, their nerves and their response to catecholamines in 1983, with Walter Osswald, and in 2001, with his research fellow Daniel Moura. The article of 2001 became his most bibliometrically successful one.
Th influence of drugs is determined not only by their pharmacodynamics, especially the existence of receptors, but also their pharmakokinetics, their fate in living tissue. This aspect was studied in Porto as well. Metabolizing enzymes, namely monoamine oxidase und catechol-O-methyl transferase (COMT), as well as carrier proteins for the transport through cell membranes contributed to the removal of catecholamines from the extracellular space, thus from the neighbourhood of the receptors, and hence to loss of effect. The role played by these processes differed between the various catecholamines and the various tissues.
One pervading difference was that inhibitors of COMT enhanced the effect of isoprenaline at β-adrenoceptors (and the ensuing blood vessel relaxation) but not the effect of noradrenaline at α-adrenoceptors (and the ensuing blood vessel contraction). Conversely inhibitors of the transport of noradrenaline into presynaptic axon terminals – cocaine being a prototype inhibitor – enhanced the effect of noradrenaline at α-, but nor the effect of isoprenaline at β-adrenoceptors. Guimarães and his coworkers concluded that the density of COMT was greater in der „biophase“ of the β-adrenoceptors than in the biophase of the α-adrenoceptors. Conversely, the density of the cocaine-sensitive transporters should be greater in the biophase of the α-adrenoceptors than the β-adrenoceptors. The hypothesis was supported by two articles in Naunyn-Schmiedeberg’s Archives of Pharmacology. In 1982, Guimarães wrote in Trends in Pharmacological Sciences: „In vascular tissue there are two different biophases for sympathomimetic agents: one for the α-adrenoceptors around the nerve terminals, where the concentration of the agonist available for the α-effect is mainly governed by uptake into these terminals; one for the β-adrenoceptors in the neighbourhood of COMT whose activity is the main factor determining the concentration of the agonist available for the β-effect.“ Rather than assuming a homogeneous distribution, pharmacologists should reckon with a very inhomogeneous distribution of catecholamines in the extracellular space, low in the immediate neighbourhood of „sites of loss“ such as transporters and enzymes, considerably higher at a distance.
A brief communication of 1981 on presynaptic β-autoreceptors became Guimarães' bibliometrically third-successful paper, and his most successful one reporting original research with new observations. Presynaptic β-autoreceptors, when activated, increase the release of the postganglionic sympathetic neurotransmitter noradrenaline and should therefore mediate a positive feedback, preceding release enhancing further release. This, however, had never been found, perhaps because the receptors are β$_2$ and therefore relatively noradrenaline-insensitive. Guimarães and coworkers, once again using veins, enriched sympathetic axon terminals with adrenaline, which is a very strong agonist at β$_2$-adrenoceptors. In this manner they indeed generated a positive feedback: the beta blocker propranolol reduced the release. The authors conclude that the introduction of adrenaline as a false transmitter „revealed the existence of a β-adrenoceptor-mediated positive feedback mechanism in this tissue.“ The interest in the discovery stems from the possibility that it explains part of the antihypertensive effect of beta blockers. In hypertension adrenaline from the adrenal medulla, getting enriched in sympathetic axon terminals, might create a pathological positive feedback with excessive release of sympathetic transmitter; beta blockers might bring release down to normal levels.
The pharmacology of angiotensin und adenosine, their receptors and their role in the pathogenesis of hypertension have been additional subjects in the Department of Pharmacology of Porto's Medical Faculty in the era of Guimarães.

## The Porto Meetings on Adrenergic Mechanisms

When the group in Porto found their main theme, they also initiated a series of meetings of similarly interested researchers, the Porto Meetings on Adrenergic Mechanisms. The first took place in 1970, with forty participants. Ten further meetings followed, in 1973, 1978, 1981, 1983, 1986, 1989, 1993, 1996, 2000 and 2003. The meetings were much smaller than the International Catecholamine Symposia begun in 1958. The Abstract book of the 1993 meeting contained 67 contributions, while that of the International Catecholamine Symposium of 1992 in Amsterdam contained 728. The exchange of ideas was the more lively. Visitors also appreciated what was only loosely connected with the scientific sessions, in 1970 when ″people in Porto still understood by a coffee break a port break″, in 1973 ″Serafim Guimarães' Coimbra fados, the fabulous dinner given by the mayor of Amarante″, in 1989 ″the unanimous wish for scopolamine oder meclizine on the Douro valley serpentine tour.“

## Teaching

Guimarães’ supplemented his lectures by co-edition of the textbook Terapêutica Medicamentosa e Suas Bases Farmacológicas (Medicines and their pharmacological basis), which appeared in six editions:
* First edition 1983, edited by von Garrett und Osswald;
* Second edition 1986, equally edited by Garrett und Osswald;
* Third edition 1999, edited by Garrett, Osswald und Guimarães;
* Fourth edition 2001, edited by Osswald und Guimarães;
* Fifth edition 2006, edited by Guimarães, Moura und Soares-da-Silva;
* Sixth edition 2014, equally edited by Guimarães, Moura und Soares-da-Silva. Porto, Porto Editora, ISBN 978-972-0-01794-9.
Guimarães has also written or co-authored several chapters, such as Sistema adrenérgico.

## Pupils

The following scientists obtained their Ph.D. under the supervision of Guimarães:
At the Medical Faculty of Porto:
* Fernando Augusto Andrade de Abreu Brandão (1980)
* Daniel Filipe Lima Moura (1988)
* José Pedro Lopes Nunes (1996)
* Manuel Joaquim Lopes Vaz da Silva (1996)
* Rosa Sousa Martins da Rocha Begonha (1999)
* Alberto Vieira da Mota (2004)
* Jorge Moreira Gonçalves (1991)
* Jorge Alberto de Barros Brandão Proença (1991)
* Helder Pinheiro (2003) –
At the Faculty of Pharmacy of the University of Coimbra:
* Isabel Vitória Neves de Figueiredo Santos Pereira (1998).

## Other activities

From 1983 to 1984 Guimarães was dean of the Medical Faculty of Porto, from 1984 to 1985 vice-rector of the University, from 1986 to 1988 founding member of the Federation of European Pharmacological Societies (EPHAR), from 1995 to 1998 president of the Sociedade Portuguesa de Farmacologia. From 1969 to 2000 he served as medical director of the spa of Monfortinho in the municipality Idanha-a-Nova, from 1972 to 1995 as counsellor of the pharmaceutical company Bial.
He is president of the advisory board of the Hospital de São João, the hospital of the Medical Faculty of the University of Porto, and president of the Liga dos Amigos do São João, the friends of the Hospital. He is a member of the advisory board for the Castelo da Feira, the Castle of Santa Maria da Feira.
He used his talent for drawing in the book, mentioned above, Retratos legendados. He published the history of the Castelo da Feira in a book, printed in 1000 copies, Castelo de Santa Maria da Feira. Medicina, Arte e Vida. His most recent book is Os Outros.

## References and notes

* 1 2 Klaus Starke (1997). "The Porto meetings on adrenergic mechanisms". Journal of Autonomic Pharmacology. 17 (4): 205–210. doi:10.1046/j.1365-2680.1997.00468.x. PMID 9373781.
* ↑ Some statements on Guimarães’ life and his pupils are taken from Serafim Guimarães.
* ↑ de:Hans-Joachim Schümann
* 1 2 Seratim Guimarães: Retratos legendados – Portraits in image and word. Universidade do Porto, Porto 2012. ISBN 978-989-746-002-9. The images are drawings by Guimarães.
* ↑ Sónia Machado (1997). "Encontros do Porto com a história da Farmacologia". Arquivos de Medicina – Revista de Ciência e Arte Médicas. 11 (6): 376–383.
* ↑ Directors of the Department were José-Maria de Oliveira (1920 to 1944), Alberto Malafaya-Baptista (1944 to 1966), José Ruiz de Almeida Garrett (1966 to 1987), Walter Osswald (1987 to 1990), Serafim Guimarães (1990 to 2005), Patrício Soares-da-Silva (since 2005). On Garrett see Serafim Guimarães (editor): Homenagem a José Ruiz de Almeida Garrett. Porto, private print 2001.
* ↑ J. Garrett, A. Malafaya-Baptista, W. Osswald (1966). "Effects of pronethalol on the cardiovascular actions of catecholamines during blockade by phenoxybenzamine". British Journal of Pharmacology. 27 (3): 459–467. doi:10.1111/j.1476-5381.1966.tb01857.x. PMC 1510922. PMID 4381965.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ S. Guimarães (1969). "Alpha excitatory, alpha inhibitory and beta inhibitory adrenergic receptors in the guinea-pig stomach". Archives Internationales de Pharmacodynamie et de Thérapie. 179 (1): 188–201. PMID 4390662.
* ↑ S. Guimarães, W. Osswald (1969). "Adrenergic receptors in the veins of the dog". European Journal of Pharmacology. 5 (2): 188–201. doi:10.1016/0014-2999(69)90021-1. PMID 4389638.
* ↑ S. Guimarães, J. P. Nunes (1990). "The effectiveness of α$_2$-adrenoceptor activation increases from the distal to the proximal part of the veins of canine limbs". British Journal of Pharmacology. 101 (2): 387–393. doi:10.1111/j.1476-5381.1990.tb12719.x. PMC 1917708. PMID 1979510.
* ↑ Walter Osswald, Serafim Guimarães (1983). "Adrenergic mechanisms in blood vessels: morphological and pharmacological aspects". Reviews of Physiology, Biochemistry and Pharmacology. 96: 53–122. doi:10.1007/BFb0031007. ISBN 978-3-540-11701-8. PMID 6338573.
* ↑ Serafim Guimarães, Daniel Moura (2001). "Vascular adrenoceptors: an update". Pharmacological Reviews. 53 (2): 319–356. PMID 11356987.
* ↑ W. Osswald, S. Guimarães, A. Coimbra (1971). "The termination of action of catecholamines in the isolated venous tissue of the dog". Naunyn-Schmiedebergs Archiv für Pharmakologie. 269 (1): 15–31. doi:10.1007/BF01422013. PMID 4252439. S2CID 35727563.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ F. Brandão, S. Guimarães (1974). "Inactivation of endogenous noradrenalin released by electrical stimulation in vitro of dog saphenous vein". Blood Vessels. 11 (1–2): 45–54. doi:10.1159/000157998. PMID 4447847.
* ↑ S. Guimarães, M. Q. Paiva (1977). "The role played by the extraneuronal system in the disposition of noradrenaline and adrenaline in vessels". Naunyn-Schmiedeberg's Archives of Pharmacology. 296 (3): 279–287. doi:10.1007/BF00498694. PMID 840321. S2CID 2786892.
* ↑ M. Q. Paiva, S. Guimarães (1978). "A comparative study of the uptake and metabolism of noradrenaline and adrenaline by the isolated saphenous vein of the dog". Naunyn-Schmiedeberg's Archives of Pharmacology. 303 (3): 221–228. doi:10.1007/BF00498047. PMID 683349. S2CID 23112047.
* ↑ Serafim Guimarães (1975). "Further study of the adrenoceptors of the saphenous vein of the dog: Influence of factors which interfere with the concentrations of agonists at the receptor level". European Journal of Pharmacology. 34 (1): 9–18. doi:10.1016/0014-2999(75)90220-4. PMID 187436.
* ↑ S. Guimarães, I. Azevedo, W. Cardoso, M. C. Oliveira (1975). "Relation between the amount of smooth muscle of venous tissue and the degree of supersensitivity to isoprenaline caused by inhibition of catechol-O-methyl transferase". Naunyn-Schmiedeberg's Archives of Pharmacology. 286 (4): 401–412. doi:10.1007/BF00506654. PMID 1095935. S2CID 28205679.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ The term „biophase“ was coined by Robert F. Furchgott for the extracellular space in the immediate vicinity of the receptors: Robert F. Furchgott (1955). "The pharmacology of vascular smooth muscle". Pharmacological Reviews. 7 (2): 184–265, hier S. 213. PMID 13245382.
* ↑ S. Guimarães, M. Q. Paiva (1981). "Two distinct adrenoceptor-biophases in the vasculature: One for α-and the other for β-agonists". Naunyn-Schmiedeberg's Archives of Pharmacology. 316 (3): 195–199. doi:10.1007/BF00505649. PMID 6114438. S2CID 46253308.
* ↑ S. Guimarães, M. Q. Paiva (1981). "Two different biophases for adrenaline released by electrical stimulation or tyramine from the sympathetic nerve endings of the dog saphenous vein". Naunyn-Schmiedeberg's Archives of Pharmacology. 316 (3): 200–204. doi:10.1007/BF00505650. PMID 6265808. S2CID 20205999.
* ↑ S. Guimarães (1982). "Two adrenergic biophases in blood vessels". Trends in Pharmacological Sciences. 3 (1): 159–161. doi:10.1016/0165-6147(82)91069-0.
* ↑ S. Guimarães, F. Brandão, M. Q. Paiva (1978). "A study of the adrenoceptor-mediated feedback mechanisms by using adrenaline as a false transmitter". Naunyn-Schmiedeberg's Archives of Pharmacology. 305 (2): 185–188. doi:10.1007/BF00508291. PMID 732895. S2CID 31581626.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ K. Starke: Pharmakologie noradrenerger und adrenerger Systeme. Pharmakotherapie des Asthma bronciale – Doping. In: K. Aktories, U. Förstermann, F. Hofmann und K. Starke: Allgemeine und spezielle Pharmakologie und Toxikologie. 11th edition, München, Elsevier GmbH 2013, Seite 153–189. ISBN 978-3-437-16888-8
* ↑ S. Guimarães, M. Q. Paiva, D. Moura (1998). "Different receptors for angiotensin II at pre- and postjunctional level of the canine mesenteric and pulmonary arteries". British Journal of Pharmacology. 124 (6): 1207–1212. doi:10.1038/sj.bjp.0701959. PMC 1565514. PMID 9720792.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Manuela Morato, Teresa Sousa, Serafim Guimarães, Daniel Moura, António Albino-Teixeira (2002). "The role of angiotensin II in hypertension due to adenosine receptors blockade". European Journal of Pharmacology. 455 (2–3): 135–141. doi:10.1016/S0014-2999(02)02587-6. PMID 12445579.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Anne-Ulrike Trendelenburg, Angelika Meyer, Werner Klebroff, Serafim Guimarães, Klaus Starke (2003). "Crosstalk between presynaptic angiotensin receptors, bradykinin receptors and α$_2$-autoreceptors in sympathetic neurons: a study in α$_2$-adrenoceptor-deficient mice". British Journal of Pharmacology. 138 (8): 1389–1402. doi:10.1038/sj.bjp.0705223. PMC 1573813. PMID 12721093.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Serafim Guimarães, Catarina Carneiro, Fernando Brandão, Helder Pinheiro, António Albino-Teixeira, Daniel Moura (2004). "A pharmacological differentiation between postjunctional (AT$_{1A}$) and prejunctional (AT$_{1B}$) angiotensin II receptors in the rabbit aorta". Naunyn-Schmiedeberg's Archives of Pharmacology. 270 (4): 262–269. doi:10.1007/s00210-004-0977-7. PMID 15448979. S2CID 24261385.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Serafim Guimarães, Helder Pinheiro (2005). "Functional evidence that in the cardiovascular system AT$_1$ angiotensin II receptors are AT$_{1B}$ prejunctionally and AT$_{1A}$ postjunctionally". Cardiovascular Research. 67 (2): 208–215. doi:10.1016/j.cardiores.2005.04.015. PMID 15953595.
* ↑ The two drugs are antiemetics.
* ↑ Serafim Guimarães: Castelo de Santa Maria da Feira. Comissão de Vigilância do Castelo de Santa Maria da Feira, 2008.
* ↑ Serafim Guimarães: Medicina, Arte e Vida, 2020.
* ↑ Serafim Guimarães: Os outros, 2024.