Increased metabolic heat production following chronic alpha-methyldopa therapy in hypertensives.
The objective of this study was to measure metabolic heat production in mild-moderate hypertensives when given chronic alpha-methyldopa for control of hypertension and to compare this with hydrochlorothiazide. Four men and one woman, age range 29-55 years, euthyroid, and not previously on alpha-methyldopa, had their drugs replaced by placebo for 4 weeks, and then alpha-methyldopa or hydrochlorothiazide was randomized single blindly to patients. The dose of each drug was increased until the ambulatory diastolic blood pressure was less than 95 mmHg (1 mmHg = 133.322 Pa), and then the dose was maintained for 20-24 weeks. The two active drugs were then crossed over, and each medication was again titrated to attain diastolic normotension (less than 95 mmHg). Maintenance was for a comparable 20-24 weeks. At week 4 (end of placebo period), weeks 20-24 (for hydrochlorothiazide or alpha-methyldopa monotherapy), and again at week 40-48 (end of cross-over period), metabolic heat production (watts), heart rate (beats per minute), and blood pressure (millimetres of Hg) were measured in a resting sitting position for 1 h in a whole body calorimeter (air temperature 28 degrees C and a dew point temperature less than 5 degrees C) for 15 experimental sessions. In four out of five patients, metabolic heat production was significantly (P less than 0.05) higher when patients were treated with alpha-methyldopa. We speculate from our data that alpha-methylnorepinephrine, the major metabolite of alpha-methyldopa, may be thermogenic and that this should be considered when the drug is prescribed.
P G
PG
Fernandez
W
W
Snedden
J W
JW
Snellen
A B
AB
Galway
C
C
Nath
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D008750:Methyldopa / Q000627:therapeutic use*; D008875:Middle Aged
D000959:Antihypertensive Agents; D008750:Methyldopa