Influence of beta-blockade on circulating plasma levels of 3-methoxy-4-hydroxy phenylethylene glycol (MHPG) during exercise in moderate hypertension.
1. The effect of exercise testing and beta-blockade on plasma norepinephrine (PNE), and secretion of its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), was assessed in 28 mild-to-moderate hypertensives before and after the administration of dilevalol, a new beta-blocker with beta 2-agonism. 2. This double blind, placebo-controlled study consisted of two successive submaximal exercise tests before and after the administration of a single oral dose of dilevalol (200 mg, 400 mg or 600 mg). Plasma norepinephrine levels were determined at rest, at 100 watts step of exercise and at maximal effort (Emax). 3. During the control test, mean PNE levels increased from 1.73 +/- 0.52 nmol/L (resting value) to 8.01 +/- 4.01 nmol/L at Emax (P less than 0.01) as MHPG levels increased from 11.18 +/- 1.33 nmol/L (rest) to 17.50 +/- 1.15 nmol/L (Emax, P less than 0.01). After dilevalol, PNE increased significantly as compared to controls (P less than 0.05), from 2.32 +/- 0.99 to 12.42 +/- 5.97 nmol/L (P less than 0.01). PNE and MHPG levels were correlated, both at rest and during exercise. PNE levels after beta-blockade were linearly related to the dose of beta-blocker administered. MHPG levels were unaltered by the administration of dilevalol, both before and after exercise. 4. The increase in MHPG that occurs during bicycle exercise is largely generated from an increase in central nervous system noradrenergic activity. While dilevalol increases the peripheral sympathetic nervous system, both at rest and during exercise (which is reflected by increases in PNE levels) the drug does not alter resting central nervous system noradrenergic activity nor amplify the increase in central noradrenergic activity that occurs during exercise.
Clinical Pharmacology Centre, Faculty of Medicine, Nice, France.
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MD
Drici
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Roux
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Candito
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Rimailho
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Morand
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Lapalus
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D007741:Labetalol / Q000494:pharmacology* / Q000627:therapeutic use; D008734:Methoxyhydroxyphenylglycol / Q000097:blood*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood
D000319:Adrenergic beta-Antagonists; D008734:Methoxyhydroxyphenylglycol; D007741:Labetalol; D009638:Norepinephrine