Age-related changes in alpha-adrenoceptor-mediated blood pressure in the rat: relationship between the potency for phenylephrine and the maximum number of binding sites.
To study the effects of aging on the blood pressure potency of phenylephrine, 6-, 10- and 40-week-old rats were used. In anesthetized rats, the potency (pD2 value) of phenylephrine on the blood pressure tended to increase with age from 6 to 10 weeks, but significantly decreased thereafter with age from 10 to 40 weeks. Similarly, in pithed rats, the potency of phenylephrine significantly increased, but decreased thereafter. In isolated rat thoracic aorta, the pD2 value of phenylephrine from the contractile responses significantly increased with age from 6 to 10 weeks, but decreased thereafter from 10 to 40 weeks. The change in the potency of phenylephrine on the blood pressure was proportional to the pD2 value of phenylephrine estimated in aortic preparations. The specific binding of [3H]prazosin to single smooth muscle cells of thoracic aorta from different aged rats was saturable. The maximum number of binding sites (Bmax) significantly increased with age from 6 to 10 weeks, but decreased thereafter from 10 to 40 weeks. However, the dissociation constant of [3H]prazosin (Kd) did not alter with age. The changes in the potencies (pD2 values) of phenylephrine on the pressure responses and on the contractile responses were proportional to the logarithm of the maximum number of binding sites. The present study suggests that age-related changes in blood pressure are due to changes in the maximum number of binding sites (receptor density) of alpha 1-adrenoceptors.
Koike
K
K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Satoh
M
M
Kanai
S
S
Ohtsuki
H
H
Takayanagi
I
I
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000375:Aging / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001665:Binding Sites / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000502:physiology*; D007553:Isotope Labeling; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010656:Phenylephrine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010656:Phenylephrine; D011224:Prazosin