Effects of nadolol on hemodynamic and hemostatic responses to potential mental and physical triggers of myocardial infarction in subjects with mild systemic hypertension.
Although beta-adrenergic blocking agents are known to reduce the risk of myocardial infarction, the mechanism of this protective effect is not well understood. The recent demonstration that beta blockers selectively blunt the increased morning risk of myocardial infarction suggests that these agents block the pathophysiologic consequences of stressors concentrated in the morning. We determined the effect of nadolol on the hemodynamic and hemostatic responses to mental stress and isometric exertion (handgrip), 2 potential triggers of infarction. The study was conducted in 15 subjects with mild systemic hypertension, using a placebo-controlled, double-blind, crossover design. Nadolol reduced systolic pressure and heart rate after mental stress. Poststress systolic pressure was 139 +/- 4 mm Hg during therapy with nadolol versus 161 +/- 4 mm Hg during placebo administration (p < 0.05). Heart rate increased to 61 +/- 2 during nadolol therapy versus 89 +/- 5 beats/min during placebo therapy (p < 0.05). The systolic pressure increase was similar during therapy with nadolol and placebo (29 +/- 2 vs 33 +/- 2 beats/min, p = NS); however, heart rate increase was less during nadolol therapy (4 +/- 1 vs 12 +/- 4 vs beats/min, p < 0.01). The responses to handgrip and their modification during nadolol therapy were similar to those observed after mental stress. Neither platelet aggregability nor fibrinolytic potential was altered by nadolol. Thus, nadolol modified hemodynamic indexes without altering the hemostatic indexes measured. This hemodynamic effect may contribute to the decrease in morning cardiovascular events by beta-adrenergic blockers and their well-documented cardioprotective effect.
Jimenez
A H
AH
Institute for Prevention of Cardiovascular Disease, New England Deaconess Hospital, Boston, Massachusetts 02215.
Tofler
G H
GH
Chen
X
X
Stubbs
M E
ME
Solomon
H S
HS
Muller
J E
JE
D000328:Adult; D001794:Blood Pressure; D002395:Catecholamines / Q000097:blood; D002940:Circadian Rhythm / Q000187:drug effects; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D005342:Fibrinolysis; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D009248:Nadolol / Q000627:therapeutic use*; D010974:Platelet Aggregation; D013312:Stress, Physiological / Q000097:blood / Q000503:physiopathology*
D002395:Catecholamines; D009248:Nadolol; D006854:Hydrocortisone