Modulation of noradrenaline release in the pithed rabbit: a role for angiotensin II.

This study in the pithed rabbit with electrically stimulated sympathetic outflow (spinal region, T-8; 3 Hz) was conducted to determine the contribution of the renin-angiotensin system to noradrenaline release in vivo. The rate of noradrenaline release (spillover) into the plasma was determined from the endogenous plasma noradrenaline level and the simultaneously determined noradrenaline plasma clearance. In the pithed rabbit, infusion of angiotensin II (0.1 microgram/kg/min i.v.) failed to increase the noradrenaline release rate and only slightly increased blood pressure. On the other hand, the angiotensin-converting enzyme inhibitor captopril (1 mg/kg i.v.) decreased both blood pressure and the noradrenaline release rate. Bilateral nephrectomy was performed to reduce endogenous angiotensin II formation; and in this case, infusion of angiotensin II markedly increased the noradrenaline release rate and blood pressure, whereas captopril had no effect on either parameter. These results suggest that angiotensin II modulates noradrenaline release in vivo through activation of facilitatory prejunctional angiotensin II receptors, and that in the pithed rabbit these receptors are probably maximally activated by endogenously synthesized angiotensin II. The actions of angiotensin II on noradrenaline release open the possibility that increases in blood pressure in the pithed rabbit--by decreasing renin release via intrarenal baroreceptors and hence decreasing angiotensin II formation--may lead to decreased noradrenaline release. This was investigated using phenylephrine (6 micrograms/kg/min i.v.), a selective alpha 1-adrenoceptor agonist, and adrenaline (1 microgram/kg/min i.v.), and alpha 1/alpha 2-agonist. Both drugs increased blood pressure and decreased the noradrenaline release rate. After bilateral nephrectomy, the inhibitory effect of phenylephrine on noradrenaline release was abolished, whereas that of adrenaline was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)