Cardiovascular adaptation to orthostatic stress during vasodilator therapy

Background: Orthostatic hypotension is a dangerous problem in elderly patients, often exacerbated by vasodilator medications. Age- and disease-related impairments in cardioacceleration and diastolic ventricular function may make older patients particularly vulnerable to the hypotensive effects of these drugs. Therefore we aimed to determine mechanisms of postural blood pressure regulation in elderly patients with coronary artery discase and to compare the effects of isosorbide dinitrate and nicardipine hydrochloride on postural blood pressure homeostasis in these patients. Methods: Twenty elderly subjects with stable coronary artery disease (age, 76 ± 4 [SD] years) underwent a baseline evaluation followed by a double-blind, randomized crossover comparison of nicardipine (20 mg by mouth t.i.d.) versus isosorbide (20 mg by mouth t.i.d.). Doppler echocardiography and a 15-minute 60-degree head-up tilt test were conducted on no study medications and then after successive 3-week treatment periods with nicardipine or isosorbide. Blood pressure, heart rate, vascular resistance, cardiac output, and spectral characteristics of heart rate and blood pressure variability were measured before and during each tilt. Results: Isosorbide treatment was associated with a higher prevalence of symptoms of cerebral hypoperfusion and a failure to increase systemic vascular resistance during tilt. While taking isosorbide subjects were able to preserve cardiac output and maintain upright blood pressure through enhanced cardioacceleration. During nicardipine treatment systemic vascular resistance and low-frequency blood pressure variability were reduced, but the ability to increase systemic vascular resistance during tilt was preserved. Conclusions: Although nicardipine may decrease vascular responsiveness to sympathetic activation, the baroreflex-mediated vasoconstrictor response to upright tilt remains intact. In contrast, isosorbide impairs the systemic vascular response to orthostatic stress in elderly patients with stable coronary artery disease.