The central pressor effect of bradykinin in normotensive and hypertensive rats

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 ED50 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 [Thi5,8,DPhe7]bradykinin. Our results show that there is a site of bradykinin action that is far more caudal than those previously described. The shorter latency and higher sensitivity of the fourth ventricle injection suggest that bradykinin injected into the lateral ventricle diffuses to the fourth ventricle where it exerts its effects.