Polipeptídeos farmacológicamente ativos e diâmetro de artérias piais: estudo experimental com vasopressina, ocitocina, bradicinina e neurocinina

Saraiva, Sylvio

doi:10.1590/S0004-282X1965000100001

Resumos

A ação de quatro polipeptídeos farmacológicamente ativos (vasopressina, ocitocina, bradicinina e neurocinina) sôbre as artérias piais foi estudada em cães anestesiados com pentobarbital sódico e preparados para o registro da pressão arterial. Utilizou-se a técnica de Forbes 25, modificada por Me-laragno37 que permite a visibilização, a fotografia e a mensuração dos referidos vasos. Foram feitas 24 experiências, divididas em 5 grupos de animais: um grupo foi utilizado como contrôle e os outros quatro para o estudo de cada uma das drogas acima referidas, administradas por via venosa. Os resultados obtidos conduziram às seguintes conclusões: 1) a vasopressina não determina variação significativa no diâmetro das artérias da pia-máter, embora tenha provocado irregulares variações da pressão arterial; 2) a ocitocina causa intensa vasoconstrição pial, de curta duração, sem contudo modificar essencialmente a pressão arterial sistêmica; 3) a bradicinina aumenta o diâmetro das artérias da pia-máter, em paralelismo com um efeito hipotensor sistêmico; 4) a neurocinina promove dilatação das artérias da pia-máter, independentemente de eventual variação da pressão arterial sistêmica.

The action of four pharmacologically active polypeptides (vasopressin, oxytocin, bradykinin and neurokinin) on the pial arteries was studied in dogs anesthetized with pentobarbital sodium, and prepared for recording the arterial pressure and measurement of the diameter of the pial vessels. Twenty four experiments were carried out by using five groups of animals : one of these groups was used as control and the remaining four were used for studying each drug, administered intravenously. These experiments led to the following conclusions: 1) vasopressin does not determine significant modification on the diameter of the arteries of the pia mater, although has provoked irregular changes on the arterial pressure; 2) oxytocin determines a marked but evanescent pial vasoconstriction, without modifying the arterial pressure; 3) bradykinin increases the diameter of the pial arteries, this enlargement being related to the duration of its hypotensive effect; 4) neurokinin dilates the arteries of the pia mater, independently of some occasional change of the systemic blood pressure.

Polipeptídeos farmacológicamente ativos e diâmetro de artérias piais. Estudo experimental com vasopressina, ocitocina, bradicinina e neurocinina

Pharmacologically active polypeptides and diameter of pial arteries. Experimental study with vasopressin, oxytocin, bradykinin and neurokinin

Sylvio Saraiva

Médico assistente da Clínica Neurológica da Faculdade de Medicina da Universidade de São Paulo (Prof. Adherbal Tolosa)

RESUMO

A ação de quatro polipeptídeos farmacológicamente ativos (vasopressina, ocitocina, bradicinina e neurocinina) sôbre as artérias piais foi estudada em cães anestesiados com pentobarbital sódico e preparados para o registro da pressão arterial. Utilizou-se a técnica de Forbes ²⁵, modificada por Me-laragno³⁷ que permite a visibilização, a fotografia e a mensuração dos referidos vasos.

Foram feitas 24 experiências, divididas em 5 grupos de animais: um grupo foi utilizado como contrôle e os outros quatro para o estudo de cada uma das drogas acima referidas, administradas por via venosa.

Os resultados obtidos conduziram às seguintes conclusões: 1) a vasopressina não determina variação significativa no diâmetro das artérias da pia-máter, embora tenha provocado irregulares variações da pressão arterial; 2) a ocitocina causa intensa vasoconstrição pial, de curta duração, sem contudo modificar essencialmente a pressão arterial sistêmica; 3) a bradicinina aumenta o diâmetro das artérias da pia-máter, em paralelismo com um efeito hipotensor sistêmico; 4) a neurocinina promove dilatação das artérias da pia-máter, independentemente de eventual variação da pressão arterial sistêmica.

SUMMARY

The action of four pharmacologically active polypeptides (vasopressin, oxytocin, bradykinin and neurokinin) on the pial arteries was studied in dogs anesthetized with pentobarbital sodium, and prepared for recording the arterial pressure and measurement of the diameter of the pial vessels.

Twenty four experiments were carried out by using five groups of animals : one of these groups was used as control and the remaining four were used for studying each drug, administered intravenously.

These experiments led to the following conclusions: 1) vasopressin does not determine significant modification on the diameter of the arteries of the pia mater, although has provoked irregular changes on the arterial pressure; 2) oxytocin determines a marked but evanescent pial vasoconstriction, without modifying the arterial pressure; 3) bradykinin increases the diameter of the pial arteries, this enlargement being related to the duration of its hypotensive effect; 4) neurokinin dilates the arteries of the pia mater, independently of some occasional change of the systemic blood pressure.

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Tese de doutoramento elaborada no Departamento de Farmacologia da Faculdade de Medicina da Universidade de São Paulo (Prof. Charles Edward Corbett).

Nota do autor - Exprimimos nossos agradecimentos aos colegas da Clínica Neurológica e do Departamento de Farmacologia da Faculdade de Medicina da Universidade de São Paulo pelo estímulo e colaboração. Ao Dr. Rubens Murillo Marques, assistente do Departamento de Estatística Aplicada da Faculdade de Higiene e Saúde Pública da Universidade de São Paulo, manifestamos nossa gratidão pela orientação na análise estatística.

Clínica Neurológica - Hospital das Clínicas da Fac. Med. da Univ. de São Paulo - Caixa Postal 3461 - São Paulo, SP - Brasil.

1. ABEL, J. J. - On the unitary versus the multiple hormone theory of posterior pituitary principles. J. Pharmacol. & Exper. Therap., 40:139-169, 1930.
2. ABEL, J. J. & KUBOTA, S. - On the presence of histamine (β iminazolylethylamina) in the hypophysis cerebri and other tissues of the body and its occurrence among the hydrolytic decomposition products of proteins. J. Pharmacol. & Exper. Therap., 13: 243-300, 1919.
3. ABEL, J. J. & NAGAYAMA, T. - On the presence of histamine in extracts of the posterior lobe of the pituitary gland and on preliminary experiments with the pressor constituent. J. Pharmacol. & Exper. Therap., 15:347-399, 1S20.
4. ABEL, J. J. & ROUILLER, C. A. - Evaluation of the hormone of the in-fundibulum of the pituitary gland in terms of histamine, with experiments on the action of repeated injections of the hormone on the blood pressure. J. Pharmacol. & Exper. Therap., 20:65-84, 1922-1923.
5. ABEL, J. J.; ROUILLER, A. & GEILING, M. K. Further investigations on the oxytocic-pressor-diuretic principle of the infundibular portion of the pituitary gland. J. Pharmacol. & Therap., 22:289-316, 1923.
6. BOISSONAS, R. A.; GUTTMANN, St. & JAQUENOUD, P. A. - Synthèse de la l-arginyl-1-propyl-l-propyl-glycyil-l-phénylalanyl-l-séryl-l-propyl-l-phénylalanyl-l-argi-nine, un nonapeptide présentant les proprietés de la bradykinine. Helv. Chim. Acta 43:1349-1358, 1960.
7. BOISSONAS, R. A.; GUTTMANN, St.; JAQUENOUD, P. A.; KONZET, H. & STURMER, E. - Synthesis and biological activity of peptides related to bradykinin. Experientia 16:326, 1960.
8. BOUCKAERT, J. J. & JOURDAN, F. - La circulation cérébrale. J. Physiol. (Paris) 41:69A-114A, 1949.
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10. CARPI, A. & CORRADO, A. P. - Cerebral vascular action of bradykinin in the dog. Experientia 17:326-327, 1961.
11. CHAPMAN, L. F.; RAMOS, A. O.; GOODELL, H.; SILVERMAN, G. & WOLFF, H. G. - A humoral agent implicated in vascular headache of migraine type. A.M.A. Arch. Neurol., 3:223-229, 1960.
12. CHAPMAN, L. F.; RAMOS, A. O.; GOODELL & WOLFF, H. G. - Neuro-humoral features of afferents fibers in man. A.M.A. Arch. Neurol., 4:617-650, 1961.
13. CHAPMAN, L. F.; RAMOS, A. O. & WOLFF, H. G. - Properties of a polypeptide formed by incubating cerebrospinal fluid with plasma globulin. Fed. Proc, 20:379, 1961.
14. CORRADO, A. P.; RAMOS, A. O. & ROCHA E SILVA, M. - Possiveis ações centrais da bradicinina. Ciência e Cultura 11:166, 1959.
15. COW, D. - Some reactions of surviving arteries. J. Physiol., 42:125-143, 1911. In Bouckaert, J. J. & Jourdan, FA
16. DALE, H. H. - On some physiological actions of ergot. J. Physiol., 34:163-206, 1906. In Dale, H. H.¹⁷
17. DALE, H. H. - The action of extracts of the pituitary body. Biochem. J., 4:427-447, 1969.
18. Du VIGNEAUD, V.; LAWLER, H. C. ,& POPENCE, E. A. - Enzymatic cleavage of glycinamide from vasopressin and a proposed structure for this pressor-antidiuretic hormone of the posterior pituitary. J. Am. Chem. Soc, 75:4880-4881, 1953.
19. Du VIGNEAUD, V.; RESSLER, Ch.; SWAN, J. M.; ROBERTS, C. W.; KATSO-YANNIS, P. G. & GORDON, S. - The synthesis of an octapeptide amide with the hormonal activity of oxytocin. J. Am. Chem. Soc, 75:4879-4880, 1953.
20. Du VIGNEAUD, V.; RESSLER, Ch.; SWAN, J. M.; ROBERTS, C. W. & KATSO-YANNIS, P. G. - The synthesis of oxytocin. J. Am. Chem. Soc, 76:3115-3121, 1954.
21. Du VIGNEAUD, V.; RESSLER, Ch. & TRIPPETT, S. - The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. J. Biol. Chem., 205:949-957, 1953.
22. DUDLEY, H. W. - Some observations on the active principles of the pituitary gland. J. Pharmacol. & Exper. Therap., 14:295-312, 1920.
23. DUDLEY, H. W. - On the active principles of the pituitary gland. J. Pharmacol. & Exper. Therap., 21:103-122, 1923.
24. FLOREY, H. W. - Microscopical observations on the circulation of the blood in the cerebral cortex. Brain 48:43-64, 1925.
25. FORBES, H. S. - The cerebral circulation. I. Observation and measurement of pial vessels. Arch. Neurol. & Psychiat., 19:751-761, 1928.
26. FORBES, H. S.; FINLEY, K. H. & NASON, G. L. - Cerebral circulation: action of epinephrine on pial vessels; action of pituitary on pial vessels; vasomotor response in the pia and in the skin. Arch. Neurol. & Psychiat., 30:957-979, 1933.
27. GADDUM, J. H. - Polypeptides which Stimulate Plain Muscle. E. & S. Livingstone, Edinburgh, 1953.
28. GOMES, F. P. - Péptidos biológicamente ativos: contribuição para o seu estudo. Tese de doutoramento. Universidade de Lisboa, 1958.
29. GRUBER, C. M. & ROBERTS, S. J. - The effect of adrenalin and other vasomotor drugs upon the cerebral blood vessels. J. Pharmacol. & Exper. Therap., 27:335-348, 1926.
30. GUIOT, G. & Le BESNERAIS, Y. - Oblitération de i'artère cérébrale moyenne sans séquelles neurologiques. Re-marques sur les facteurs influençant l'éfficacité des anastomoses périphériques. Neu-rochirurgie 1:286-291.
31. HOWE, H. S. & McKINLEY, E. - Cerebral circulation. Arch. Neurol. & Psychiat., 18:81-86, 1927.
32. HOWELL, W. H. - The physiological effects of extracts of the hypophysis cerebri and infundibular body. J. Exper. Med., 3:245, 1898. In Graybiel, A. .& Glendy, E. - Circulatory effects following the intravenous administration of pitressin in normal persons and in patients with hypertension and angina pectoris. Am. Heart J., 21:481-489, 1941.
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15 Ago 2013
Data do Fascículo
Mar 1965

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[1] 1. ABEL, J. J. - On the unitary versus the multiple hormone theory of posterior pituitary principles. J. Pharmacol. & Exper. Therap., 40:139-169, 1930.

[2] 2. ABEL, J. J. & KUBOTA, S. - On the presence of histamine (β iminazolylethylamina) in the hypophysis cerebri and other tissues of the body and its occurrence among the hydrolytic decomposition products of proteins. J. Pharmacol. & Exper. Therap., 13: 243-300, 1919.

[3] 3. ABEL, J. J. & NAGAYAMA, T. - On the presence of histamine in extracts of the posterior lobe of the pituitary gland and on preliminary experiments with the pressor constituent. J. Pharmacol. & Exper. Therap., 15:347-399, 1S20.

[4] 4. ABEL, J. J. & ROUILLER, C. A. - Evaluation of the hormone of the in-fundibulum of the pituitary gland in terms of histamine, with experiments on the action of repeated injections of the hormone on the blood pressure. J. Pharmacol. & Exper. Therap., 20:65-84, 1922-1923.

[5] 5. ABEL, J. J.; ROUILLER, A. & GEILING, M. K. Further investigations on the oxytocic-pressor-diuretic principle of the infundibular portion of the pituitary gland. J. Pharmacol. & Therap., 22:289-316, 1923.

[6] 6. BOISSONAS, R. A.; GUTTMANN, St. & JAQUENOUD, P. A. - Synthèse de la l-arginyl-1-propyl-l-propyl-glycyil-l-phénylalanyl-l-séryl-l-propyl-l-phénylalanyl-l-argi-nine, un nonapeptide présentant les proprietés de la bradykinine. Helv. Chim. Acta 43:1349-1358, 1960.

[7] 7. BOISSONAS, R. A.; GUTTMANN, St.; JAQUENOUD, P. A.; KONZET, H. & STURMER, E. - Synthesis and biological activity of peptides related to bradykinin. Experientia 16:326, 1960.

[8] 8. BOUCKAERT, J. J. & JOURDAN, F. - La circulation cérébrale. J. Physiol. (Paris) 41:69A-114A, 1949.

[9] 9. BOUCKAERT, J. J. & JOURDAN, F. - Réactions pharmacologiques des vaisseaux cérébraux. Compt. rend. Soc. biol., 120:790-792, 1935.

[10] 10. CARPI, A. & CORRADO, A. P. - Cerebral vascular action of bradykinin in the dog. Experientia 17:326-327, 1961.

[11] 11. CHAPMAN, L. F.; RAMOS, A. O.; GOODELL, H.; SILVERMAN, G. & WOLFF, H. G. - A humoral agent implicated in vascular headache of migraine type. A.M.A. Arch. Neurol., 3:223-229, 1960.

[12] 12. CHAPMAN, L. F.; RAMOS, A. O.; GOODELL & WOLFF, H. G. - Neuro-humoral features of afferents fibers in man. A.M.A. Arch. Neurol., 4:617-650, 1961.

[13] 13. CHAPMAN, L. F.; RAMOS, A. O. & WOLFF, H. G. - Properties of a polypeptide formed by incubating cerebrospinal fluid with plasma globulin. Fed. Proc, 20:379, 1961.

[14] 14. CORRADO, A. P.; RAMOS, A. O. & ROCHA E SILVA, M. - Possiveis ações centrais da bradicinina. Ciência e Cultura 11:166, 1959.

[15] 15. COW, D. - Some reactions of surviving arteries. J. Physiol., 42:125-143, 1911. In Bouckaert, J. J. & Jourdan, FA

[16] 16. DALE, H. H. - On some physiological actions of ergot. J. Physiol., 34:163-206, 1906. In Dale, H. H.¹⁷

[17] 17. DALE, H. H. - The action of extracts of the pituitary body. Biochem. J., 4:427-447, 1969.

[18] 18. Du VIGNEAUD, V.; LAWLER, H. C. ,& POPENCE, E. A. - Enzymatic cleavage of glycinamide from vasopressin and a proposed structure for this pressor-antidiuretic hormone of the posterior pituitary. J. Am. Chem. Soc, 75:4880-4881, 1953.

[19] 19. Du VIGNEAUD, V.; RESSLER, Ch.; SWAN, J. M.; ROBERTS, C. W.; KATSO-YANNIS, P. G. & GORDON, S. - The synthesis of an octapeptide amide with the hormonal activity of oxytocin. J. Am. Chem. Soc, 75:4879-4880, 1953.

[20] 20. Du VIGNEAUD, V.; RESSLER, Ch.; SWAN, J. M.; ROBERTS, C. W. & KATSO-YANNIS, P. G. - The synthesis of oxytocin. J. Am. Chem. Soc, 76:3115-3121, 1954.

[21] 21. Du VIGNEAUD, V.; RESSLER, Ch. & TRIPPETT, S. - The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. J. Biol. Chem., 205:949-957, 1953.

[22] 22. DUDLEY, H. W. - Some observations on the active principles of the pituitary gland. J. Pharmacol. & Exper. Therap., 14:295-312, 1920.

[23] 23. DUDLEY, H. W. - On the active principles of the pituitary gland. J. Pharmacol. & Exper. Therap., 21:103-122, 1923.

[24] 24. FLOREY, H. W. - Microscopical observations on the circulation of the blood in the cerebral cortex. Brain 48:43-64, 1925.

[25] 25. FORBES, H. S. - The cerebral circulation. I. Observation and measurement of pial vessels. Arch. Neurol. & Psychiat., 19:751-761, 1928.

[26] 26. FORBES, H. S.; FINLEY, K. H. & NASON, G. L. - Cerebral circulation: action of epinephrine on pial vessels; action of pituitary on pial vessels; vasomotor response in the pia and in the skin. Arch. Neurol. & Psychiat., 30:957-979, 1933.

[27] 27. GADDUM, J. H. - Polypeptides which Stimulate Plain Muscle. E. & S. Livingstone, Edinburgh, 1953.

[28] 28. GOMES, F. P. - Péptidos biológicamente ativos: contribuição para o seu estudo. Tese de doutoramento. Universidade de Lisboa, 1958.

[29] 29. GRUBER, C. M. & ROBERTS, S. J. - The effect of adrenalin and other vasomotor drugs upon the cerebral blood vessels. J. Pharmacol. & Exper. Therap., 27:335-348, 1926.

[30] 30. GUIOT, G. & Le BESNERAIS, Y. - Oblitération de i'artère cérébrale moyenne sans séquelles neurologiques. Re-marques sur les facteurs influençant l'éfficacité des anastomoses périphériques. Neu-rochirurgie 1:286-291.

[31] 31. HOWE, H. S. & McKINLEY, E. - Cerebral circulation. Arch. Neurol. & Psychiat., 18:81-86, 1927.

[32] 32. HOWELL, W. H. - The physiological effects of extracts of the hypophysis cerebri and infundibular body. J. Exper. Med., 3:245, 1898. In Graybiel, A. .& Glendy, E. - Circulatory effects following the intravenous administration of pitressin in normal persons and in patients with hypertension and angina pectoris. Am. Heart J., 21:481-489, 1941.

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Brasil

Brasil

Polipeptídeos farmacológicamente ativos e diâmetro de artérias piais: estudo experimental com vasopressina, ocitocina, bradicinina e neurocinina

Pharmacologically active polypeptides and diameter of pial arteries: experimental study with vasopressin, oxytocin, bradykinin and neurokinin

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