Kallikrein-Kinins in the Central Nervous System

Scicli, A. G.; Forbes, Glenn S.; Nolly, H; Dujovny, M; Carretero, Oscar A.

doi:10.3109/10641968409046068

Cited by 60 publications

(28 citation statements)

References 14 publications

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“…The identified components include bradykinin (BK), 1 kallikrein, 2 angiotensin converting enzyme or kininase II, 3 and BK immunoreactive neuronal systems. 4 When injected intracerebroventricularly, BK itself produces a range of effects such as behavioral arousal and sedation accompanied by electroencephalographic alterations, 5 cardiovascular changes, 6 and antidiuretic action.…”

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confidence: 99%

The central pressor effect of bradykinin in normotensive and hypertensive rats.

1988

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SUMMARY The site of action for the pressor response to bradykinin administered into the lateral ventricle has been reported to be either in the septal area or in the ventral portion of the third ventricle. We obtained dose-response curves for the pressor effect of bradykinin injected into the lateral ventricle or the posterior region of the fourth ventricle of normotensive Wistar and spontaneously hypertensive rats (SHR). Responses to fourth ventricle injections had a shorter latency and larger maximal effect, and were 20 to 100 times greater than those to lateral ventricle injections, suggesting that the site of bradykinin's action is in the caudal region of the brain, probably close to the area postrema. Maximal effects were similar for lateral and fourth ventricle injections in both SHR and normotensive rats, but SHR were much more sensitive to bradykinin. The EDg, values for the lateral ventricle route in normotensive rats and SHR were 1.3 and 0.35 nmol, respectively, and, for the fourth ventricle route, 60 and 3.4 pmol, respectively. Responses to Lys-Lys-bradykinin, a kininase-resistant bradykinin analogue, showed that kininase activity is lower in SHR than in normotensive rats and that SHR are four times more sensitive to Lys-Lys-bradykinin than are normotensive rats. The responses of all rats were inhibited by a specific bradykinin receptor blocker [Thi

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confidence: 99%

The central pressor effect of bradykinin in normotensive and hypertensive rats.

1988

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“…4 - 25 We found that human CSF contains small amounts of kininogen. 6 Although the data clearly suggest that increases in brain kinins mediate the cardiovascular effects of melittin, we could not obtain evidence that CSF withdrawn from the cisterna magna at the end of the melittin infusion contains large amounts of kinins. These data contrast with those obtained by Thomas et al, 5 who performed ventriculocisternal perfusions in dogs and found that melittin increased kinins several times in the perfusate.…”

Section: Figure 3 Line Graphs Showing Effect Of Intracerebroventricumentioning

confidence: 66%

“…1 -3 A messenger RNA (mRNA) that codes for a kallikrein-like enzyme 4 has been isolated from brain homogenates; kininogen and free kinins are found in the cerebrospinal fluid (CSF) in dogs and humans, 5 - 6 and several enzymes capable of inactivating kinins are found in the central nervous system as well. heart rate 9 -10 as well as the release of antidiuretic hormones.…”

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confidence: 99%

Role of endogenous brain kinins in the cardiovascular response to intracerebroventricular melittin.

et al. 1989

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Intracerebroventricular infusion of the peptide melittin increases immunoreactive kinins in the cerebrospinal fluid of anesthetized dogs, probably secondary to activation of brain or cerebrospinal fluid kininogenases. Intracerebroventricular melittin also increases blood pressure and heart rate, possibly mediated by brain kinins, since intracerebroventricular bradyklnin also increases blood pressure and heart rate. We tested whether the effects of centrally administered melittin on blood pressure and heart rate could be blocked by simultaneous infusion of a kinin receptor antagonist, ]bradykinin, in normotensive awake rats. In the controls, intracerebroventricular infusion of kinin receptor antagonist given for 1 hour at a rate of 10 /tg/hr blocked bradykinin-induced increases in blood pressure and heart rate by 80%. Basal blood pressure and heart rate were not affected by the kinin receptor antagonist alone. After a 30-minute infusion of melittin (8 /tg/30 min), cerebrospinal fluid kininogenase activity (n=17) rose from 0.13±0.05 to 0.43±0.1 ng/ml/min (/»<0.02). Although cerebrospinal fluid kinins increased from below sensitivity (0.02 ng/ml, n=12) to 0.19±0.1 ng/ml (n=17), this change was due to drastic increases in three rats, whereas in 12 of them kinins were below sensitivity. Incubation of bradykinin (10 ng) with 0.1 ml rat cerebrospinal fluid for 5 minutes destroyed 70% of kinins, suggesting that rapid destruction may have made detection of increased CSF kinins difficult. In normotensive awake rats (n=8), intracerebroventricular melittin increased blood pressure from 110.8±1.8 to 131.5±1.4 mm Hg (p<0.01) and heart rate from 378.8±5.8 to 430.0±8 beats/min (p<0.01). Simultaneous intracerebroventricular infusion of kinin receptor antagonist (10 /tg/hr) partially but significantly blunted the blood pressure response to melittin; blood pressure increased to 122.5±2.5 mm Hg (/?<0.001, melittin vs. melittin+kinin receptor antagonist) and heart rate decreased to 343.8 ±11.2 beats/min (p<0.01 vs. basal and/><0.001 vs. melittin). Pretreatment with intracerebroventricular meclofenamate (a prostaglandin synthesis inhibitor) abolished the blood pressure and heart rate response to melittin. The long-lasting hypertensive effect of melittin may be due to prostanoids, since a bolus intracerebroventricular injection of prostaglandin Ej (500 ng) induced long-lasting hypertension. In summary, intracerebroventricular melittin increased the cerebrospinal fluid concentration of kallikrein without a concomitant increase in kinins. Kinin receptor antagonist diminished the hypertensive response induced by melittin and converted melittin-induced tachycardia to bradycardia. Meclofenamate also blocked the cardiovascular response to melittin. These results suggest that the cardiovascular response to intracerebroventricular melittin is mediated by activation of the endogenous kallikrein-kinin system in the brain, and ultimately by prostaglandins. We conclude that the brain kallikrein-kinin system, once activated, can markedly influence...

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“…Both these sys tems work by the mechanism of stress response and produce peptides having an immunomodulant effect. In drug-addicted pregnancies psychophysical and pharmacological stress causes an involvement of the neuroendocrinological and immune systems [15][16][17][18][19][20][21]. Moreover, the kinine-kininase system is involved in the microvascular adaptation to stress [22,23].…”

Section: Drug-addicted Pregnant Patientsmentioning

confidence: 99%

Drug Addiction in Pregnancy: 13 Years of Experience

Noia

Santis²,

Fundarò³

et al. 1994

Fetal Diagn Ther

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In this retrospective study, we review our data on 203 drug-addicted pregnant patients, considering two different aspects of the question: maternal and fetal. We report the findings relative to maternal metabolic, endocrinological, neuroendocrinological and immunological studies performed in our department over the past 13 years. Moreover, we study fetal involvement in drug-addicted pregnancy and report the findings of our fetal behavior and urodynamic studies. The last section of this study deals with perinatal outcome. In particular, we report a high incidence of small-for-gestational-age fetuses and premature deliveries.

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Kallikrein-Kinins in the Central Nervous System

Cited by 60 publications

References 14 publications

The central pressor effect of bradykinin in normotensive and hypertensive rats.

The central pressor effect of bradykinin in normotensive and hypertensive rats.

Role of endogenous brain kinins in the cardiovascular response to intracerebroventricular melittin.

Drug Addiction in Pregnancy: 13 Years of Experience

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