Central vasomotor stimulation by angiotensin

SUMMARY 1. When angiotensin was infused at low rates into the vertebral arteries of anaesthetized dogs, it raised the blood pressure. When infused at similar rates intravenously or into the internal carotid artery it either did not change blood pressure, or raised it only very slightly. The difference in response was highly significant over the range of 1-50 ng kg- ' min- '. 2. During intravenous infusion at higher rates, angiotensin usually produced the well-known reflex bradycardia and fall of cardiac output, but on infusion into the vertebral arteries it rapidly raised systemic arterial pressure, often increased heart rate, and usually produced a transient increase of cardiac output. 3. Angiotensin by both routes raised peripheral resistance, but noradrenaline, by contrast, produced the same response whether it was given into the vertebral arteries or into a vein. 4. These observations suggest that part of the pressor effect of intravenous angiotensin may be mediated by a direct stimulation of some part of the hind brain. There are several means by which angiotensin may raise systemic arterial pressure. In addition to its direct arterial vasoconstrictor action, it can release catecholamines from the adrenal medulla (Braun-Menhdez, Fasciolo, Leloir & Muiioz, 1940), stimulate or facilitate transmission in sympathetic ganglia (Lewis & Reit, 1966) and enhance the peripheral vasoconstrictor response to endogenously released noradrenaline (McCubbin & Page, 1963a, b). In very large doses it was reported, 9 years ago, to cause central stimulation of the sympatho-adrenal system when infused into the the dog's cerebral circulation which was isolated and perfused from another animal (Bickerton & Buckley, 1961). The special importance of the vertebral artery territory in mediating the central stimulatory effects of angiotensin, and the extreme sensitivity to angiotensin when given into the vertebral artery, was first observed in conscious rabbits (Dickinson, 1965; Yu & Dickinson, 1965) and in anaesthetized rabbits after blood