Neural mechanisms in primary hypertension. Efficacy of alpha-blockade with doxazosin during stress.
This single-blind study assessed the role of the sympathetic nervous system in primary hypertensives, at rest and during stress, and examined blood pressure responses to an alpha 1-blocker, doxazosin. Twenty patients were selected who had a sitting diastolic blood pressure 95 to 115 mm Hg at the end of the placebo period. Doxazosin was given in doses of 1 mg per day initially, then increased weekly to 2, 4, 8, and 16 mg, until goal blood pressure or maximum dose was reached or side effects limited further increase. Their determined dose of doxazosin was held constant for 16 weeks of the maintenance period. Mental and isometric stress tests were performed at the end of placebo and at the first and last months of maintenance. Diastolic blood pressures were related to baseline plasma norepinephrine, r = 0.61, P < .01. The dose of doxazosin administered was 8.4 +/- 4.1 mg. After 4 months of therapy, doxazosin lowered blood pressure from 147 +/- 16/99 +/- 3 to 135 +/- 5/87 +/- 8 sitting, and from 146 +/- 14/99 +/- 6 to 130 +/- 14/86 +/- 7 standing, respectively. Heart rates were not changed. The reduction of standing systolic blood pressure was related to baseline norepinephrine in the 12 patients who reached goal blood pressure, r = 0.57, P < .05. During mental and isometric stress tests, the percentage changes of blood pressures were related to their baseline plasma norepinephrine. Doxazosin reduced the percentage increments of blood pressure during mental stress 12.2 +/- 5.7/11.8 +/- 4.3% versus 5.7 +/- 1.0/8.1 +/- 7.4%, P < .01/.05. Doxazosin also blunted the diastolic blood pressure response to isometric exercise from 18.3 +/- 12.2% to 9.3 +/- 11.0%, P < .05. Neurogenic factors participate in the elevation of blood pressure in some patients with primary hypertension. The alpha-blocker doxazosin was effective in 60% of the hypertensive patients--it controlled blood pressure during laboratory stress, suggesting particular value in reduction of blood pressure during ambient stress of everyday living.
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University of Southern California School of Medicine, Los Angeles 90033, USA.
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DeQuattro
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D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D017292:Doxazosin / Q000627:therapeutic use*; D015444:Exercise; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D016037:Single-Blind Method; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D000317:Adrenergic alpha-Antagonists; D017292:Doxazosin; D009638:Norepinephrine