Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension

Background Human studies have shown that the blood pressure lowering effect s of angiotensin converting enzyme inhibitors are accompanied by a reductio n in plasma norepinephrine levels. Whether this is due to central or periph eral mechanisms is unknown, however. Objective To evaluate the effects of chronic interference with the renin-an giotensin system on sympathetic nerve traffic and baroreflex control of vag al and adrenergic cardiovascular drive. Patients and methods In 18 untreated mild to moderate essential hypertensiv e patients aged 48.5 +/- 1.9 years (mean +/- SEM), we measured mean arteria l pressure (Finapres), heart rate (electrocardiogram), plasma renin activit y (radioimmunoassay), plasma norepinephrine (high-performance liquid chroma tography) and postganglionic muscle sympathetic nerve activity (microneurog raphy at a peroneal nerve). In nine patients, measurements were performed b efore and after 2 months of oral administration of lisinopril (10 mg/day), while in the remaining nine patients they were performed before and after a 2 month observation period, without the drug administration. Measurements were performed at rest and during baroreflex stimulation and deactivation e licited by stepwise intravenous infusions of phenylephrine and nitroprussid e, respectively. Results Lisinopril induced a marked increase in plasma renin activity (from 1.1 +/- 0.2 to 6.4 +/- 1.3 ng/ml per h, P< 0.01) and a reduction in mean a rterial pressure (from 109.6 +/-: 3.1 to 98.7 +/- 2.9 mmHg, P< 0.01) withou t affecting the heart rate. Plasma norepinephrine and muscle sympathetic ne rve activity values were not significantly different before and after lisin opril treatment (plasma norepinephrine values changed from 290.4 +/- 39.2 t o 308.1 +/- 67.1 pg/ml; muscle sympathetic nerve activity changed from 56.4 +/- 5.3 to 50.6 +/- 6.6 bursts/100 heart beats). Neither the sympathoinhib itory nor the sympathoexcitatory responses to phenylephrine and nitroprussi de were affected by lisinopril, nor the concomitant bradycardia and tachyca rdia, The curves relating mean arterial pressure to heart rate and muscle s ympathetic nerve activity values during baroreceptor manipulation were shif ted to the left, indicating a resetting of the baroreflex to the lower bloo d pressure values achieved during treatment Conclusions In essential hypertension, sympathetic nerve traffic is not aff ected by chronic angiotensin converting enzyme inhibitor treatment that eff ectively interferes with the renin-angiotensin system and lowers the elevat ed blood pressure. The baroreflex ability to modulate heart rate and centra l sympathetic outflow is also unaffected. These data argue against the exis tence of a central sympathoexcitatory effect of angiotensin II in this cond ition. They also indicate that antihypertensive treatment with an angiotens in converting enzyme inhibitor preserves autonomic reflex control, with fav orable consequences for cardiovascular homeostasis. (C) Lippincott Williams & Wilkins.