Desensitization of beta-adrenoceptor- and prostaglandin E1 receptor-mediated human vascular smooth muscle relaxation.
Regulation of beta-adrenoceptors in animal tissues and human cell cultures has been extensively described; on the other hand, relatively little is known about regulation of beta-adrenoceptors in human tissues in vivo. Both beta-adrenoceptors and the prostaglandin E1 (PGE1) receptors stimulate vasodilation. We wondered if prolonged infusion of isoproterenol or PGE1 would cause desensitization of smooth muscle relaxation and used the dorsal hand-vein compliance technique to investigate this question. After constructing a dose-response curve to either the beta-agonist isoproterenol or to PGE1 in a phenylephrine preconstricted vein, isoproterenol (271 ng/min), PGE1 (956 pg/min), or saline was infused for 4 h in separate experiments. There was no change in the ED50 or Emax for either isoproterenol or PGE1 after saline infusion. After a 4-h infusion of isoproterenol, the maximal vasodilator response to isoproterenol was significantly (p less than 0.01) attenuated from 61 +/- 33% to 19 +/- 10%, while the ED50 significantly increased (p less than 0.01) from a geometric mean of 37 to 197 ng/min. After infusion of isoproterenol, the mean maximum PGE1-induced venorelaxation of 129 +/- 29% was modestly but significantly (p less than 0.05) blunted to 96 +/- 35%, while the ED50 of PGE1 increased significantly (p less than 0.01) from a geometric mean of 81 to 398 pg/min. A 4-h infusion of PGE1 significantly (p less than 0.01) attenuated the maximum response to PGE1 from 73 +/- 35 to 28 +/- 16%. The maximal vasodilatory response to isoproterenol was also significantly blunted (p less than 0.05) from 62 +/- 35 to 42 +/- 41%, with no change in ED50.(ABSTRACT TRUNCATED AT 250 WORDS)
Vincent
J
J
Division of Clinical Pharmacology, Stanford University Medical Center, California 94305.
Blaschke
T F
TF
Hoffman
B B
BB
D000527:Alprostadil / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006225:Hand / Q000098:blood supply; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology / Q000648:ultrastructure*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology*; D018078:Receptors, Prostaglandin E; D012680:Sensitivity and Specificity; D013997:Time Factors; D014680:Veins / Q000502:physiology / Q000648:ultrastructure
D011943:Receptors, Adrenergic, beta; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D000527:Alprostadil; D007545:Isoproterenol