The centrally induced effects of
angiotensin II and
substance P on the cardiovascular system and on neuronal efferent activity of the splanchnic, renal, and adrenal nerves were investigated in chronically instrumented conscious rats. The pressor responses to
substance P injected into the lateral brain ventricle were accompanied by marked and short latency increases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a rise in plasma
noradrenaline and
adrenaline. Behaviorally, an arousal-type reaction was observed. In contrast, the pressor responses to intracerebroventricular
angiotensin II were associated with initial decreases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a fall in plasma
noradrenaline at the time of the maximal blood pressure increase. In some but not all animals, a second blood pressure peak associated with increases in heart rate and splanchnic nerve activity was observed after several minutes. Incomplete chronic sinoaortic baroreceptor deafferentiation prevented the
angiotensin II-induced fall in heart rate but not the initial fall in splanchnic nerve activity. The decreases in splanchnic nerve activity also occurred in
diabetes insipidus rats and persisted in Long Evans rats after vascular
vasopressin receptor blockade with
d(CH2)5AVP, despite marked reductions of the pressor responses in both groups. Peripheral alpha-
adrenoceptor blockade with
prazosin or
ganglion blockade with
hexamethonium inhibited the central
angiotensin II pressor responses only in combination with
vasopressin receptor blockade. On the other hand, either
sympatholytic drug, alone, abolished the pressor responses in the
diabetes insipidus rats. This indicates that in intact conscious rats the central pressor effects of
angiotensin II are initiated by
vasopressin release but become dependent on the sympathetic nervous system when
vasopressin is absent or not effective. When rats were allowed to drink in response to
angiotensin II, a further sharp rise in blood pressure occurred, together with increases in heart rate and splanchnic nerve activity. The results demonstrate fundamental differences in the mechanisms by which central pressor
peptides can influence cardiovascular and autonomic function. It is conceivable that the distinct sympathetic response patterns to central
angiotensin II and
substance P receptor stimulation form part of a specific cardiovascular adjustment to the individual behavioral reactions, such as drinking, as in the case of
angiotensin II, or arousal within the central processing of
pain, as in the case of
substance P.