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  • Title: Estimated affinity of isoproterenol to cardiac chronotropic beta-receptor and of phenylephrine to vasoconstrictive alpha-receptor of the systemic resistance vessels in human borderline hypertension.
    Author: Ito H, Tonai N, Hirakawa S.
    Journal: Jpn Circ J; 1983 Feb; 47(2):240-55. PubMed ID: 6298482.
    Abstract:
    There has been yet no report, to our knowledge, which clarified the affinity ("sensitivity") of catecholamines to cardiac chronotropic beta-adrenergic receptor or to vasoconstrictive alpha-adrenergic receptor of skeletal muscle resistance vessels in human borderline hypertension (BHT), using an analysis of the kinetics of the drug-receptor interaction. In the first half of this study, isoproterenol (ISO) infusion test was performed on "normal" subjects (n = 12) and subjects with BHT (n = 10). Dose-response relation was obtained in terms of various doses of ISO and the increments of heart rate (deltaHR) produced by ISO. In the latter half of this study, phenylephrine (PHE) infusion test was carried out in the series of "normal" subjects (n = 5) and subjects with BHT (n = 6), a partly different series from the first series of subjects. Dose-response relation, again, was obtained in terms of various doses of PHE and the increments of total peripheral resistance (deltaTPR) produced by PHE. These relations were displayed on Lineweaver-Burk's plot and the "affinity" of ISO to cardiac chronotropic beta-receptor or that of PHE to vasoconstrictive alpha-receptor of skeletal muscle resistance vessels was estimated, graphically, assuming that 1) drugs were diluted by a volume of body fluid equal to the blood volume which was actually measured in each individual and 2) this concentration of drugs existed around the receptor site, i.e., there was no significant individual variations in terms of the metabolism and the distribution of the drugs. Estimated "affinity" of ISO to cardiac chronotropic beta-receptor was 0.168 +/- 0.014 x 10(4) ml X ug-1 (mean +/- SE, n = 10) in patients with BHT, while it was 0.170 +/- 0.015 x 10(4) (n = 12) in "normal" subjects. Estimated "affinity" of PHE to vasoconstrictive alpha-receptor of skeletal muscle resistance vessels was 0.171 +/- 0.011 x 10(2) ml X ug-1 (n = 6) in patients with BHT, while it was 0.183 +/- 0.012 x 10(2) (n = 5) in "normal" subjects. It is concluded from these data, almost fairly, that there is no difference in terms of the estimated "affinity" of ISO to cardiac chronotropic beta-receptor or that of PHE to vasoconstrictive alpha-receptor between "normal" subjects and patients with BHT. It was also found, in PHE infusion tests, that the plasma adrenaline concentration was significantly higher in patients with BHT than in "normal" subjects, at least at two points of time in the test: a) immediately before PHE infusion, when every individual appeared to be considerably restful and b) at the end of 1-2 min after the completion of the infusion of the largest dose of PHE used.
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