Investigation of reflexes from volume and baroreceptors during converting-enzyme inhibition in humans This article emphasizes the importance of testing baroreceptor and cardiopulmonary receptor control of circulation during angiotensin-converting enzyme (ACE) inhibitor treatment in hypertensive!%, because removal of angiotensin II-dependent stimulation of the sympathetic nervous system could impair reflex blood pressure homeostasis. In essential hypertensive subjects, the sympathetic vasoconstriction that occurs in skeletal muscle after deactivation of cardiopulmonary receptors was reduced after short-term or prolonged administration of the ACE inhibitor, captopril. However, another sympathetic target of the cardiopulmonary reflex, that is, renin release, was unaltered by both short-term and prolonged administration of captopril. Furthermore, the blood pressure and heart rate influences of arterial baroreceptors were preserved or even enhanced after administration of captopril. Thus important reflex mechanisms for cardiovascular homeostasis are not adversely affected by ACE inhibition, which preserves blood pressure levels during gravity challenges or exercise. Preliminary data suggest that this may be even more evident for benazepril. (AM HEART J 1989;117:740.) Cristina Giannattasio, MD, Guido Grassi, MD, Gino Seravalle, MD, Albert0 Morganti, MD, Albert0 Zanchetti, MD, and Giuseppe Mancia, MD. Milan, Italy Data from animals and humans suggest that the blood pressure-lowering effect of angiotensin-con- verting enzyme (ACE) inhibitors in hypertension depends on the following three mechanisms: (1) blocking the formation of angiotensin II from its precursor, thereby preventing its marked influence on vasomotor tone and aldosterone secretion’; (2) reducing the breakdown of tissue and plasma brady- kinin, thereby enhancing its vasodilator effect?; and (3) altering the metabolism of kallikreins and pros- taglandins in a way that also results in vasodilata- tion.3 Another mechanism for the antihypertensive effect of ACE inhibitors is removal of the facilitating effect of angiotensin II on sympathetic vasoconstric- tor influences4 However, this may also have adverse consequences, since the sympathetic nervous system represents the final pathway of reflexes involved in blood pressure and blood volume homeostasis. Thus it is important to evaluate these reflexes during the From the Cattedra di Semeiotica Medica e Istituto di Clinica Medica Generale e Terapia Medica, Universiti di Milano and Centro di Fisiologia Clinica e Ipertensione, Ospedale Maggiore. Reprint requests: Giuseppe Mancia, MD, Centro Fisiologia e Ipertensione, Via F. Sforza 35 20122 Milano, Italy. administration of ACE inhibitors in humans to ensure that their possible impairment does not cause untoward hemodynamic effects. We have done this with captopril, and this article summarizes the results. CARDIOPULMONARY RECEPTOR REFLEXES In humans, volume receptors located in the heart and lungs and presumably innervated by vagal fibers exert a reflex tonic inhibition on sympathetic vasoconstrictor tone to skeletal muscle and splanch- nit circulation, complementing arterial barorecep- tors in preservation of blood pressure homeostasis.5 Furthermore, they tonicahy restrain renal sympa- thetic activity and renin release, thus playing a role in blood volume homeostasis.6p1 The cardiopulmonary receptor reflexes were stud- ied in subjects with untreated essential hyperten- sion of mild or moderate degree who had plasma renin activity in the lower or mid portion of the normal range. 8, g As shown in Table I, blood pressure (sphygmomanometry), heart rate (ECG), forearm vascular resistance (mean arterial pressure divided by plethysmographically measured forearm blood- flow), plasma norepinephrine (radioenzymatic method on venous blood samples), plasma renin 740