Regulation of alpha 2-adrenoceptor density in normotensive and hypertensive man.
We examined normotensive and hypertensive subjects in order to determine whether changes in platelet alpha 2-adrenoceptor density following alterations in plasma noradrenaline are related to changes in noradrenaline (NA) reactivity. Noradrenaline reactivity, plasma NA, alpha 2-adrenoceptor density, and adenylate cyclase activity were measured before and after a 24-h infusion of NA at a subpressor dose (0.02 micrograms/kg per min, n = 13), and also after application of drugs known to increase (nifedipine and furosemide) or decrease (clonidine) plasma NA. Measurements were obtained 60 min after nifedipine (20 mg in a single dose, n = 13), after 3 weeks on furosemide (30 mg twice a day, n = 8) and after 1 week on clonidine (150 micrograms three times a day, n = 5). Infusion of NA decreased alpha 2-adrenoceptor density (P less than 0.01) and NA reactivity (P less than 0.05). Nifedipine decreased alpha 2-adrenoceptor density and NA reactivity (P less than 0.01 for both) in patients with essential hypertension. The alterations in alpha 2-adrenoceptor densities were paralleled by a decreased adrenaline-induced inhibition of adenylate cyclase activity (P less than 0.01). Furosemide decreased alpha 2-adrenoceptor density (P less than 0.01), the fraction of high-affinity binding sites (P less than 0.01) and NA reactivity (P less than 0.05) in normotensive subjects. Following clonidine all three parameters, alpha 2-adrenoceptor density, the fraction of high affinity sites and NA reactivity, increased (P less than 0.05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)
Fritschka
E
E
Department of Medicine, Klinikum Steglitz, Freie Universität Berlin, Federal Republic of Germany.
Kribben
A
A
Hoyer
J
J
Rothschild
M
M
Thiede
H M
HM
Distler
A
A
Philipp
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood* / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D005665:Furosemide; D000262:Adenylyl Cyclases; D009543:Nifedipine; D003000:Clonidine; D009638:Norepinephrine