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

Abstract

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 (B_max) significantly increased with age from 6 to 10 weeks, but decreased thereafter from 10 to 40 weeks. However, the dissociation constant of [³H]prazosin (K_d) 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 α₁-adrenoceptors.

Role of α1-adrenergic vasoconstriction in the regulation of skeletal muscle blood flow with advancing age

“…Based on the distinct pattern of conduit vessel vasoconstriction and LBF changes in response to PE, we speculate that the number of functional ␣ 1 -receptors may be reduced in the CFA of the elderly, and that the predominant site of ␣ 1 -adrenergic regulation is thus found in the distal resistance vasculature of the leg. This concept is supported by animal work identifying an age-related reduction in ␣ 1 -receptor density in large-conduit arteries, such as the rat aorta (14,38).…”

Effects of aging on adipose resistance artery vasoconstriction: possible implications for orthostatic blood pressure regulation

“…Second, there may be chronic elevations in sympathetic activity to white adipose tissue with aging, possibly contributing to a diminution of ␣-adrenergic receptor density in the blood vessels within this tissue. This possibility appears more likely, since a reduction in the number of ␣ 1receptor binding sites (18) and blunted ␣-adrenergic vasoconstriction (5) have been reported in the aorta of aged rats.…”

High-Intensity Exercise Promotes Deleterious Cardiovascular Remodeling in a High-Cardiovascular-Risk Model: A Role for Oxidative Stress

“…Interestingly, in our model, PHE-induced contraction decreased in all high-risk groups compared with 10-week-old lean rats, likely due to a senescent vascular phenotype in aged, 36-week-old rats accruing several risk factors. Aging is associated with a decrease in the number of phenylephrine receptors in aortic VSMCs [23], leading to a decreased vascular contractile response [23,24]. Similarly, insulin resistance impinges endothelial function and VSMCs and promotes a blunted response to PHE [25].…”