We hypothesised that depression of the cardiac baroreceptor reflex by angiotensin II (ANGII) in the NTS is mediated via activation of nitric oxide synthase (NOS) and subsequent release of GABA (Paton et al. 2001). To test this hypothesis, we have recorded from identified baroreceptive NTS neurones, and determined how their barosensitivity is altered by ANGII alone or in the presence of either a NOS inhibitor or GABA_A receptor antagonist.

Experiments were performed in the in situ working heart-brainstem preparation of the rat (Paton, 1996). Rats were anaesthetized deeply in a saturated atmosphere of halothane and failed to respond to a noxious pinch of the tail. NTS neurones were recorded using a triple-barrelled microelectrode. The recording barrel was filled with NaCl (2 M) and the remaining barrels with 10 µM ANGII and either the NOS inhibitor L-NAME (20 mM) or the GABA_A receptor antagonist bicuculline (100 µM). Drugs were ejected using pressure. Baroreceptive NTS neurones were identified by their firing response to distension of the aortic arch, using a balloon tipped catheter, or inflation of a carotid sinus by injection of Ringer solution via a double lumen cannula that allowed measurement of carotid sinus pressure. Additional NTS neurones were identified that responded to peripheral chemoreceptor activation by aortic injection of sodium cyanide (7-30 µg). Data are expressed as means ± S.E.M. Statistical significance was determined using Student’s paired t test.

Baroreceptor stimulation increased neuronal activity from 3.3 ± 0.9 to 10.8 ± 1.2 Hz (n = 28, P < 0.01). Of these neurones, ANGII either inhibited baroreceptor activation by 56.9 ± 6 % (n = 20) or increased baroreceptor-induced activation (146.4 ± 12.9 % control; n = 4) or produced no change (96.9 ± 3.4 % control; n = 4). L-NAME did not alter the baroreceptor-evoked activation of NTS neurones (91.7 ± 7.6% P = 0.4), but prevented the ANGII-induced depression (n = 7, P = 0.94). Similarly, bicuculline prevented the depressant effects of ANGII (n = 4; P = 0.47). In contrast, AII potentiated the chemoreceptor-evoked firing responses in 9 of 10 neurones (146.2 ± 17.4 %, P < 0.05). L-NAME had no effect on the chemoreceptor-evoked response or its potentiation by ANGII. Bicuculline potentiated the chemoreceptor-evoked response, although co-application with ANGII did not further potentiate this response (n = 2).

Our results support the hypothesis that in the NTS ANGII-induced depression of the baroreceptor reflex depends on the activation of NOS and release of GABA acting on GABA_A receptors. ANGII-evoked potentiation of chemoreceptive NTS neurones is not dependent on NO synthase.

Australian Heart Foundation and British Heart Foundation funded research.