Cardiovascular Effects Produced by Bradykinin Microinjection into the Nucleus Tractus Solitarii of Anesthetized Rats

In this study, we characterized the cardiovascular effects produced by microinjection of doses in the femtomole range of bradykinin (BK) into the nucleus tractus solitarii of male Wistar rats (230-280 g, n = 120) anesthetized with urethane (1.2 g/kg, i.p.). Microinjections of BK (1, 10, 100 fmol, and 1 and 10 pmol, in 50 nl) or vehicle (NaCl, 0.9%) were made by using a triple-barreled glass micropipette into the medial nTS (0.4 mm anterior, 0.3 mm lateral to the obex and 0.3 mm deep from the dorsal surface). Microinjection of BK produced a shallow dose-dependent decrease in mean arterial pressure and heart rate reaching -18 +/- 6 mmHg and -21 +/- 5 beats/min, with the dose of 10 pmol. The peripheral mechanism of these effects, tested in animals treated with methylatropine (2 mg/kg, i.v.), or propranolol (2 mg/kg, i.v.) or prazosin (30 micrograms/kg, i.v.), was shown to be mainly dependent on an increase in vagal efferent activity for bradycardia and a decrease in sympathetic activity for hypotension. In order to investigate the receptor subtype involved in these effects, BK was microinjected into the nTS before and after the injection of the B1 receptor antagonist, Des-Arg9-Leu8-BK (DALBK) (11.5 pmol) or before and after the B2 receptor antagonist, HOE-140 (7.7 pmol). The cardiovascular effects of BK were significantly attenuated by the microinjection of HOE-140 and DALBK into the nTS. The effect of BK microinjected into the nTS on the baroreflex modulation was also investigated. While BK produced a significant facilitation of the baroreflex, HOE-140 and DALBK produced a significant attenuation of the baroreceptor control of heart rate. Taken together, the data presented in this study indicate the nTS as a site, in the central nervous system, for the modulatory effect of BK on the central cardiovascular control.