Alpha-methylDOPA dissociates hypertension, cardiovascular reactivity and emotional behavior in spontaneously hypertensive rats

The purpose of the present study was to determine whether the centrally-acting hypotensive agent, alpha-methylDOPA (MD), in addition to lowering tonic or resting blood pressure (BP), suppresses the phasic increases in BP which accompany emotional arousal. Spontaneously hypertensive rats (SHRs), chronically instrumented for computer-assisted recording of BP and heart rate (HR) from the aorta while awake and unrestrained, were subjected to classical fear conditioning. The next day, BP and HR were recorded before and 2 h following treatment (i.p.) with MD (3.75 mg/kg,n = 7; 7.5 mg/kg,n = 7; 15 mg/kg,n = 10; 30 mg/kg,n = 1060 mg/kg,n = 9; 120 mg/kg,n = 9; 240 mg/kg,n = 10) or saline (2 ml,n = 10). Immediately thereafter, blood pressure and heart rate responses to the conditioned emotional stimulus were assessed. Additional SHRs were treated with MD (30 mg/kg, n = 10; 60 mg/kg, n = 10) or saline (2 ml, n = 10) 2 hr prior to assessment of conditioned fear behavior (duration of immobilization or freezing behavior during a 300 s presentation of the conditioned emotional stimulus). Resting BP in saline controls was 160 ± 5, and doses of MD of 7.5 mg/kg or more resulted in a dose-dependent suppression of resting BP, with the maximal hypotensive change (47 ± 5) produced by 60 mg/kg. The conditioned pressor response (averaged over the 10 s stimulus) was 17 ± 3 mm Hg in saline controls and was systemically reduced in groups treated with 15 mg/kg or more of MD, with the minimal response (maximal suppression) achieved by 60 mg/kg (4 ± 1 mm Hg). Correlation analysis of the effects of MD on resting BP and on the conditioned BP response resulted in a low coefficient of correlation (4 = -0.22). Freezing (in s) was not different in saline controls (160 ± 25) and animals treated with 30 mg/kg (170 ± 25) or 60 mg/kg (214 ± 11) of MD. MD thus suppresses the emotion-induced elevation of BP, independent of effects on resting BP and without altering emotional behavior. These findings suggest that MD is capable of regulating both basal BP and BP reactivity in hypertension, though through separate actions, and that central alpha-adrenergic mechanisms are involved in the autonomic, but not the behavioral, manifestation of emotional arousal.