Brain kinins are responsible for the pressor effect of intracerebroventricular captopril in spontaneously hypertensive rats.

The role of the brain kallikrein-kinin system in the regulation of arterial blood pressure of normotensive and spontaneously hypertensive rats was evaluated. Intracerebroventricular administration of the kinin antagonist [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin caused no change in mean blood pressure in Wistar-Kyoto, Sprague-Dawley, or spontaneously hypertensive rats. The antagonist proved to be very potent in blocking the pressor effect of intracerebroventricular bradykinin (32 +/- 3 vs. 3 +/- 1 mm Hg, p less than 0.01). It was specific, as the pressor effect induced by other unrelated peptides was similar during the infusion of either vehicle or kinin antagonist (angiotensin II, 25 +/- 4 vs. 26 +/- 2 mm Hg; prostaglandin E2, 48 +/- 3 vs. 47 +/- 8 mm Hg; norepinephrine, 17 +/- 2 vs. 18 +/- 2 mm Hg; leucine-enkephaline, 15 +/- 2 vs. 16 +/- 1 mm Hg; neurotensin, 18 +/- 2 vs. 19 +/- 1 mm Hg; substance P, 19 +/- 2 vs. 19 +/- 2 mm Hg). Intracerebroventricular administration of 1 mg captopril, an inhibitor of kininase II (one of the enzymes responsible for kinin degradation), caused no change in mean blood pressure in normotensive rats, whereas it increased mean blood pressure by 44 +/- 9 mm Hg (p less than 0.01) in spontaneously hypertensive rats. This increase in mean blood pressure was blocked and then reversed into a hypotensive effect (22 +/- 6 mm Hg, p less than 0.05) during the infusion of kinin antagonist. Our data suggest that the pressor effect induced by intracerebroventricular captopril is due to a transient elevation in endogenous brain kinin levels, supporting the hypothesis that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure in spontaneously hypertensive rats.

[1]  L. Chao,et al.  A major difference of kallikrein-binding protein in spontaneously hypertensive versus normotensive rats. , 1988, Journal of hypertension.

[2]  C. J. Lindsey,et al.  The Central Pressor Effect of Bradykinin in Normotensive and Hypertensive Rats , 1988, Hypertension.

[3]  H. Margolius,et al.  Afferent vagal stimulation, vasopressin, and nitroprusside alter cerebrospinal fluid kinin. , 1987, The American journal of physiology.

[4]  R. Skidgel,et al.  The Unusual Substrate Specificity and the Distribution of Human Angiotensin I Converting Enzyme Special Lecture , 1986 .

[5]  M. Phillips,et al.  Converting enzyme inhibitors and brain angiotensin. , 1986, Journal of cardiovascular pharmacology.

[6]  D. Diz.  Bradykinin and related peptides in central control of the cardiovascular system , 1985, Peptides.

[7]  D. Ganten,et al.  Kinin-forming activity in rat brain , 1985, Neurochemistry International.

[8]  T. Sasaki,et al.  Regional Distribution and Characterization of Kinin in the CNS of the Rat , 1985, Journal of neurochemistry.

[9]  J. Stewart,et al.  Competitive antagonists of bradykinin , 1985, Peptides.

[10]  S. Chai,et al.  In vitro autoradiographic localization of angiotensin-converting enzyme in rat brain using 125I-labelled MK351A. , 1984, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[11]  S H Snyder,et al.  Identification of Bradykinin in Mammalian Brain , 1984, Journal of neurochemistry.

[12]  T. Unger,et al.  Is Tissue Converting Enzyme Inhibition a Determinant of the Antihypertensive Efficacy of Converting Enzyme Inhibitors? Studies with the Two Different Compounds, Hoe498 and MK421, in Spontaneously Hypertensive Rats , 1984, Journal of cardiovascular pharmacology.

[13]  H. Margolius,et al.  Cerebrospinal fluid kinins and cardiovascular function. Effects of cerebroventricular melittin. , 1984, Hypertension.

[14]  M. Dujovny,et al.  Kallikrein-kinins in the central nervous system. , 1984, Clinical and experimental hypertension. Part A, Theory and practice.

[15]  L. Chao,et al.  Identification of tissue kallikrein in brain and in the cell-free translation product encoded by brain mRNA. , 1983, The Journal of biological chemistry.

[16]  W. Hoffman,et al.  Angiotensin II and bradykinin: interactions between two centrally active peptides. , 1983, The American journal of physiology.

[17]  C. Sumners,et al.  Central Pressor Action of Neurotensin in Conscious Rats , 1982, Hypertension.

[18]  Y. Tsuda,et al.  The disappearance rate of intraventricular bradykinin in the brain of the conscious rat. , 1982, Biochemical and biophysical research communications.

[19]  K. Kariya,et al.  Effects of intraventricular injection of bradykinin on the EEG and the blood pressure in conscious rats , 1981, Neuropharmacology.

[20]  Hakuo Takahashi.  Exaggerated Sympathetic Responses to Bradykinin in Spontaneously Hypertensive Rats , 1981, Hypertension.

[21]  H. Okamoto,et al.  Regional Distribution of Kininase in Rat Brain , 1981, Journal of neurochemistry.

[22]  D. Ganten,et al.  Central blood pressure effects of substance P and angiotensin II: role of the sympathetic nervous system and vasopressin. , 1981, European journal of pharmacology.

[23]  T. Unger,et al.  Brain converting enzyme inhibition: a possible mechanism for the antihypertensive action of captopril in spontaneously hypertensive rats. , 1981, European journal of pharmacology.

[24]  H. Takahashi,et al.  Centrally induced cardiovascular and sympathetic nerve responses to bradykinin in rats. , 1981, The Journal of pharmacology and experimental therapeutics.

[25]  A. White,et al.  Activation of membrane-bound kallikrein and renin in the kidney. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[26]  D. Ganten,et al.  Enkephalin Effects on Blood Pressure, Heart Rate, and Baroreceptor Reflex , 1980, Hypertension.

[27]  A. Doyle,et al.  Blood Pressure Responses of Conscious Normotensive and Spontaneously Hypertensive Rats to Intracerebroventricular and Peripheral Administration of Captopril , 1980, Hypertension.

[28]  J. Stamler,et al.  The central and peripheral effects of Captopril (SQ 14225) on the arterial pressure of the spontaneously hypertensive rat , 1980, Brain Research.

[29]  W. Hoffman,et al.  Separation of pressor and antidiuretic effects of intraventricular bradykinin , 1978, Neuropharmacology.

[30]  A. E. Fisher,et al.  Ventricular obstruction: effect on drinking induced by intracranial injection of angiotensin , 1975, Science.

[31]  E. G. Erdös,et al.  Angiotensin I converting enzyme. , 1975, Circulation research.

[32]  F. Graeff,et al.  Central mechanisms of the hypertensive action of intraventricular bradykinin in the unanaesthetized rat. , 1974, Neuropharmacology.

[33]  A. Sjoerdsma,et al.  Norepinephrine Metabolism in Brainstem of Spontaneously Hypertensive Rats , 1970, Science.

[34]  H. Iwata,et al.  Pharmacological significances of peptidase and proteinase in the brain. 4. Effect of bradykinin on the central nervous system and role of the enzyme inactivating bradykinin in mouse brain. , 1970, Japanese journal of pharmacology.

[35]  H. Iwata,et al.  Pharmacological significances of peptidase and proteinase in the brain. I. Enzymatic inactivation of bradykinin in rat brain. , 1969, Biochemical pharmacology.

[36]  J.de Groot,et al.  The rat forebrain in stereotaxic coordinates , 1959 .