title: Cardiovascular and neurohumoral postural responses and baroreceptor abnormalities during a course of adjunctive vasodilator therapy with felodipine for congestive heart failure.
abstract: Studies in patients with congestive heart failure (CHF) have demonstrated an abnormal beta-adrenergic reflex vasodilation during orthostatic tilt. Baroreflex modulation of vascular resistance in patients with CHF was investigated during therapy with a vasoselective calcium antagonist, felodipine. Eight patients on conventional therapy for severe CHF were studied after a 3 week course of additional felodipine or placebo treatment under randomized, double-blind, and crossover conditions. Forearm subcutaneous vascular resistance (FSVR) was estimated with use of the local 133Xe washout. Aortic pulsatile stretch, expressed as the systolic distension in percent of diastolic diameter, was calculated from echocardiographic measurements of aortic root diameters. At 3 weeks, felodipine reduced the arterial pressure, systemic vascular resistance, and FSVR, preserved cardiac filling pressures and heart rate, and increased cardiac output, stroke volume, and aortic pulsatile stretch. Upright tilt (45 degrees) was used to study baroreflex-mediated cardiovascular responses. The unloading of cardiopulmonary baroreceptors during upright tilt was substantial and about equal during both treatment courses, but the pulse pressure was maintained during the placebo and decreased during the felodipine period. During tilt, the patients on placebo failed to increase heart rate and their FSVR, systemic vascular resistance, and arterial mean pressure were decreased, whereas during tilt after felodipine, heart rate and systemic vascular resistance increased to maintain arterial mean pressure and FSVR also tended to increase. Both the stroke volume and aortic pulsatile stretch increased during tilt in patients on placebo but they decreased in those on felodipine. The tilt caused increments in circulating norepinephrine and epinephrine levels during both treatment regimens. Regulation of FSVR during the sympathetic stimulation of orthostatic stress was further elucidated. Proximal neural blockade caused an increase in FSVR during tilt in patients on placebo and a decrease in FSVR during tilt in those on felodipine. Local beta-adrenoceptor blockade caused similar increments in FSVR during tilt in patients on both treatments. Combined proximal and local blockade still increased FSVR during tilt in those on placebo, but caused no change in FSVR during tilt in those on felodipine. This study demonstrates that felodipine normalizes baroreflex control of vascular resistance in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000368:Aged; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D015736:Felodipine; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000502:physiology*; D009568:Nitrendipine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009638:Norepinephrine / Q000097:blood; D011187:Posture; D011311:Pressoreceptors / Q000187:drug effects* / Q000503:physiopathology; D011897:Random Allocation; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D018377:Neurotransmitter Agents; D014665:Vasodilator Agents; D009568:Nitrendipine; D015736:Felodipine; D009638:Norepinephrine; D004837:Epinephrine