Effects of nisoldipine on stress-induced changes in haemodynamics and plasma catecholamines in normotensives and hypertensives.
In a double-blind, placebo-controlled crossover study 10 mg nisoldipine was given orally twice daily for 3.5 days to 12 normotensives and 12 essential hypertensives. In each study period, subjects were exposed to 6 min of physical exercise and 3 min of mental stress following the morning dose on day 3 and 4, respectively. Blood pressure, heart rate, systolic time intervals (day 3 only) and plasma levels of noradrenaline, adrenaline, dopamine as well as dihydroxyphenylglycol (DOPEG; the main presynaptic metabolite of noradrenaline) were determined at rest and at the end of both tests. Nisoldipine increased resting heart rate in normotensives and hypertensives, but reduced resting BP and BP during mental stress in hypertensives only. It also increased plasma concentrations of noradrenaline and DOPEG at rest and plasma noradrenaline concentrations during mental stress in both groups. However, nisoldipine affected neither exercise- nor stress-induced changes in any of the parameters monitored here. There was a correlation between the drug-induced percentage fall in resting BP and the height of BP during placebo treatment. While the resting values of plasma DOPEG were higher in hypertensives than in normotensives, those of plasma noradrenaline were not. Consequently, the linear relationship that existed between the resting plasma concentrations of DOPEG and noradrenaline in both groups was shifted to higher DOPEG levels in hypertensives when compared with normotensives. In conclusion, the effectiveness of nisoldipine in lowering BP was the more pronounced the higher the BP to begin with. Nisoldipine did not attenuate exercise- or stress-induced increases in plasma catecholamines. Essential hypertension may be associated with an enhanced presynaptic formation of DOPEG.
Ludwig
J
J
Medizinische Poliklinik, University of Würzburg, Federal Republic of Germany.
Gerhardt
T
T
Halbrügge
T
T
Walter
J
J
Heidbreder
E
E
Graefe
K H
KH
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood*; D004298:Dopamine / Q000097:blood; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D015444:Exercise; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D008875:Middle Aged; D015737:Nisoldipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D013315:Stress, Psychological / Q000503:physiopathology
D002395:Catecholamines; D015737:Nisoldipine; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine