Long‐term Sympatho‐excitatory Effect of Angiotensin Ii: A Mechanism of Spontaneous and Renovascular Hypertension

The peptide hormone angiotensin II (AngII) is acknowledged to be an important factor in the pathophysiology of hypertension. This is particularly the case in hypertension caused by luminal narrowing of one renal artery, (i.e. renovascular hypertension). The primary mechanism by which AngII raises blood pressure, however, is disputed. Strong arguments can be made supporting either vascular contraction, effects on renal excretion of sodium and water, or trophic actions on cardiovascular structures as the key element. In this paper I review evidence that AngII influences blood pressure by modulating autonomic nervous system activity. Modulation can occur at both the peripheral and central aspects of the autonomic system, but I focus on brain pathways involved in determining sympathetic nervous system activity. 2. Experimental and clinical investigations are cited to support the hypothesis that sympathetically mediated pressor effects are increased by both circulating and brain-derived AngII in hypertension. Recent work points specifically to sympathetic pre-motor neurons in the rostral ventrolateral medulla (RVLM) as a critical site of action of brain AngII in normotensive and hypertensive animals. 3. This same set of neurons appears to be an important relay in the sympatho-excitatory response to circulating AngII initiated at circumventricular organs, particularly the area postrema. AngII has important effects on the baroreflex. These do not mediate the sympatho-excitation elicited by circulating AngII, but rather mask its expression. 4. Substantial data support the hypothesis that increased blood concentrations of AngII in renovascular hypertension elevate blood pressure by causing neurogenic vasoconstriction mediated through the area postrema and RVLM.