Beta-adrenergic receptors and reflex tachycardia after single and repeated felodipine administration in essential hypertension.
To verify the possible contribution of beta-adrenergic receptor down-regulation to the reversal of reflex tachycardia during chronic treatment with a dihydropyridine calcium antagonist, 11 hypertensive patients were studied with noninvasive blood pressure (BP) and heart rate (HR) monitoring after a placebo period, and on the first and seventh day of felodipine administration, 5 mg twice daily. Plasma catecholamines and neutrophil beta-adrenergic receptors were measured on the first and seventh day of treatment, immediately before and 2 h after drug administration. The first administration of felodipine was followed by a significant drop in BP (peak reduction in mean BP 24 +/- 7 mm Hg), lasting 6 h and mirrored by reflex tachycardia (peak increase in HR 14 +/- 9 beats/min). On the morning of the seventh day, 12 h after the previous felodipine administration, mean BP (MBP) was 16 mm Hg lower than on the last placebo day, while HR was unchanged. The next administration of felodipine was followed by a smaller drop in BP (MBP - 15 +/- 7 mm Hg; NS vs. placebo), while reflex tachycardia was the same as after acute felodipine (HR 13 +/- 8 beats/min; p less than 0.05 vs. placebo, NS vs. acute administration). Plasma noradrenaline concentration increased after both acute and chronic administration (p less than 0.0001), and preadministration values were highest on day 7 (p less than 0.05). Neutrophil beta-adrenergic receptor density and affinity did not change either acutely or chronically. This study gives both indirect and direct evidence that beta-adrenoceptor down-regulation does not occur during repeated felodipine administration in hypertension. Reflex tachycardia is not abolished, but is reset to lower BP levels.
Savonitto
S
S
Servizio di Endocrinologia, Ospedale Luigi Sacco, Milan, Italy.
Bevilacqua
M
M
Chebat
E
E
Vago
T
T
Bertora
P
P
Baldi
G
G
Renesto
E
E
Peruzzi
E
E
Sardina
M
M
Norbiato
G
G
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D015736:Felodipine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000187:drug effects; D016037:Single-Blind Method; D013268:Stimulation, Chemical
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D015736:Felodipine