Cerebrospinal fluid kinins and cardiovascular function. Effects of cerebroventricular melittin.
Biochemical and histochemical studies have identified components of the kallikrein-kinin system in the brain. The present study was designed to determine whether kinins could be detected in cerebrospinal fluid (CSF) and if these levels could be altered. Endogenous CSF samples were taken from the cisterna magna of pentobarbital-anesthetized mongrel dogs (n = 11) and were shown to contain 13 +/- 3 pg/ml (mean +/- SE) of immunoreactive kinin ( ikinin ) measured by RIA. The ( ikinin ) samples showed complete parallelism to standard synthetic bradykinin. Ventriculocisternal perfusion of the anesthetized dog brain with artificial CSF alone at a rate of 0.191 ml/min for 240 minutes had little or no effect on basal levels of CSF ( ikinin ), mean arterial pressure (MAP), or heart rate (HR). Melittin (20 microM), an activator of membrane-bound kallikrein, added to the perfusion system for 60 minutes caused a significant and sustained elevation in CSF ( ikinin ) levels from 19 pg/ml up to a maximum of 194 pg/ml (p less than 0.01). This change was accompanied by a prolonged increase in MAP of up to 22 mm Hg (p less than 0.01) and a transient increase in HR of 14 bpm (p less than 0.05). Melittin (2 microM) had no significant effect on CSF ( ikinin ) levels or MAP, but resulted in a sustained increase in HR of 17 to 25 bpm (p less than 0.01). The cardiovascular responses to centrally administered melittin (20 microM) were attenuated by concomitant administration of aprotinin (2000 KIU/ml). This study establishes the existence of ( ikinin ) in the CSF, shows that such levels can be manipulated, and suggests that central kinins may be involved in the modulation of cardiovascular function.
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001514:Bee Venoms / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D005260:Female; D007276:Injections, Intraventricular; D007700:Kinetics; D007705:Kinins / Q000134:cerebrospinal fluid*; D008297:Male; D008555:Melitten / Q000008:administration & dosage / Q000494:pharmacology*; D011863:Radioimmunoassay / Q000379:methods
D001514:Bee Venoms; D007705:Kinins; D008555:Melitten; D007611:Aprotinin