(Hypertension. 1998;31:378.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
Neural and Hypotensive Effects of Angiotensin II Receptor Blockade
Division of Cardiology, Mount Sinai Hospital, and the Centre for Cardiovascular Research, University of Toronto, Ontario, Canada.
Correspondence to John S. Floras, Division of Cardiology, Mount Sinai Hospital; Suite 1614; 600 University Avenue; Toronto, Ontario M5G 1X5, Canada
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 conducted a randomized double-blind crossover trial in nine young healthy men (aged 33±3 [mean±SE] years) studied in the absence of salt restriction, comparing the effect of 1 week treatment with the angiotensin II receptor antagonist losartan (100 mg daily) against placebo with respect to the following variables, recorded during supine rest: intra-arterial blood pressure (BP), heart rate (HR), forearm vascular resistance and norepinephrine appearance rate, total body norepinephrine spillover, variability of BP and HR (spectral analysis), and baroreflex sensitivity 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) after 1 week of placebo and 112±6/61±3 mm Hg after 1 week of losartan (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). Losartan had no effect on HR (60±3 on placebo versus 59±2 beats per minute with losartan), total body norepinephrine spillover (3.0±0.8 versus 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 variability spectra or on baroreflex sensitivity for HR. Endogenous angiotensin II contributes to the maintenance of supine BP in normal subjects, studied in the absence of sodium restriction. The fall in BP caused by losartan is accompanied by a resetting of the baroreflex regulation of HR and sympathetic outflow, but baroreflex sensitivity for heart rate is not altered. Therefore, the reduction in BP observed after short-term angiotensin type 1 receptor antagonism may be achieved through a direct effect on vascular tone rather than through a primary reduction in sympathetic outflow.
Key Words: baroreceptor reflexes • blood pressure • heart rate variability • humans • losartan • norepinephine kinetics • sympathetic nervous system
Abbreviations: AT1 = angiotensin II type 1 (receptor) • BP = blood pressure • DBP = diastolic blood pressure • FBF = forearm blood flow • HR = heart rate • NE = norepinephrine • SBP = systolic blood pressure • U = resistance units
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