Role of endogenous brain kinins in the cardiovascular response to intracerebroventricular melittin.
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 bradykinin 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, [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin, in normotensive awake rats. In the controls, intracerebroventricular infusion of kinin receptor antagonist given for 1 hour at a rate of 10 micrograms/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 micrograms/30 min), cerebrospinal fluid kininogenase activity (n = 17) rose from 0.13 +/- 0.05 to 0.43 +/- 0.1 ng/ml/min (p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Yang
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XP
Department of Medicine, Henry Ford Hospital, Detroit, Michigan 48202.
Carretero
O A
OA
Jacobsen
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G
Scicli
A G
AG
D000818:Animals; D001514:Bee Venoms / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000031:analogs & derivatives; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D008555:Melitten / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D001514:Bee Venoms; D062367:ortho-Aminobenzoates; C058532:HOE k86-4321; D008555:Melitten; D008469:Meclofenamic Acid; D007610:Kallikreins; D015232:Dinoprostone; D001920:Bradykinin