NEURAL AND HYPOTENSIVE EFFECTS OF ANGIOTENSIN-II RECEPTOR BLOCKADE

Angiotensin II participates in the neural regulation of the heart and circulation at both central and peripheral sites. To explore the role of endogenous angiotensin II in blood pressure regulation, we conducte d a randomized double-blind crossover trial in nine young healthy men (aged 33+/-3 [mean+/-SE] years) studied in the absence of salt restric tion, comparing the effect of 1 week treatment with the angiotensin II receptor antagonist losartan (100 mg daily) against placebo with resp ect to the following variables, recorded during supine rest: intra-art erial blood pressure (BP), heart rate (HR), forearm vascular resistanc e and norepinephrine appearance rate, total body norepinephrine spillo ver, variability of BP and HR (spectral analysis), and baroreflex sens itivity for HR (gain of the transfer function from systolic BP to HR). Blood pressure was 119+/-7/66+/-4 mm Hg (systolic BP/diastolic BP) af ter 1 week of placebo and 112+/-6/61+/-3 mm Hg after 1 week of losarta n (P<.05). Forearm Vascular resistance tended to fall, from 42.3+/-6.9 U on placebo to 32.8+/-5.0 U, with losartan treatment (P=.07). Losart an had no effect on HR (60+/-3 on placebo versus 59+/-2. beats per min ute with losartan), total body norepinephrine spillover (3.0+/-0.8 ver sus 3.3+/-1.2 nmol/min), forearm norepinephrine appearance rate (3.8+/ -1.1 versus 5.3+/-1.1 pmol/100 mL forearm tissue per minute), power in the high-or low-frequency components of the HR variability and BP var iability spectra or on baroreflex sensitivity for HR. Endogenous angio tensin II contributes to the maintenance of supine BP in normal subjec ts, studied in the absence of sodium restriction The fall in BP caused by losartan is accompanied by a resetting of the baroreflex regulatio n of HR and sympathetic outflow, but baroreflex sensitivity for heart rate is not altered. Therefore, the reduction in BP observed after sho rt-term angiotensin type 1 receptor antagonism may be achieved through a direct effect on vascular tone rather than through a primary reduct ion in sympathetic outflow.