Therapy and Prevention Pharmacology

Nine normal volunteers underwent assessment of renal, forearm, and hormonal responses to orthostasis (quiet standing) in the presence and absence of 1 week of oral propranolol (160 mg/day). This was done to test the hypothesis that physiologic decrements in renal function (glomerular filtration rate, effective renal plasma flow, and absolute urinary sodium excretion) are attenuated by propranolol during quiet standing. The present studies, however, demonstrate that propranolol exaggerates the physiologic decrement in glomerular filtration rate, effective renal plasma flow, and absolute urinary sodium excretion during orthostasis. Forearm and renal vascular resistances were also accentuated in the presence of propranolol during quiet standing. These responses were associated with significant increases in plasma norepinephrine. We conclude that long-term administration of propranolol accentuates the physiologic decrement in renal hemodynamic and excretory function as well as in the forearm hemodynamic response to orthostasis in normal subjects. Circulation 74, No. 5, 1061-1065, 1986. ORTHOSTASIS in man activates complex reflex and hormonal responses that preserve arterial pressure during a decrease in venous return. 1'2 While reflex-mediated tachycardia and increased peripheral vascular resistance maintain arterial pressure over the short term, the renal response, characterized by a reduction in hemodynamic and excretory function, may be viewed as a more long-term mechanism for maintenance of arterial pressure by increasing extracellular fluid volume. The renal hemodynamic and excretory response during orthostasis (i.e., quiet standing) in normal humans in the presence and absence of long-term /8adrenoreceptor blockade has not been examined. Since cardiopulmonary reflexes exert their greatest inhibitory influence on renal function,` quiet standing was chosen as a maneuver that would unload both ventricular mechanoreceptors, as a result of a decrease in venous return, and activate somatic reflexes as a result of sustained muscle contraction in the lower extremities. From the Departments of Medicine and Physiology and Biophysics, Mayo Medical School. Supported by a grant from the American Heart Association (86-767) and from the National Institutes of Health (HL07269), as well as grants from the Hearst and Mayo Foundations. Address for correspondence: John C. Burnett, Jr., M.D., Division of Cardiovascular Diseases and Internal Medicine, Mayo Medical School, Rochester, MN 55905. Received Nov. 14, 1985; revision accepted Aug. 14, 1986. *Current address: Division of Nephrology, University of Chicago Hospital dnd Clinics, Chicago, IL 60637. Inasmuch as propranolol has been reported to alter the sensitivity of cardiovascular reflexes both over the short and long term,7-9 the present study was designed to examine the renal hemodynamic and excretory response to orthostasis in the presence and absence of long-term propranolol.