Racial differences in lymphocyte beta-receptor sensitivity to propranolol.
Differences between blacks and whites in their antihypertensive response to beta-blocker therapy are well recognized although the mechanisms of these response differences are not entirely understood. This study was performed to evaluate racial differences in in vitro sensitivity of lymphocyte beta-receptors to beta-blockade. Lymphocytes were isolated from whole blood of 10 white and 8 black healthy male volunteers and were exposed to isoproterenol concentrations ranging from 10(-8) M to 10(-2) M. Isoproterenol stimulation studies were performed in both the presence and absence of a typical therapeutic concentration of 1-propranolol (15 nM). Cyclic AMP content was determined by radioimmunoassay and was corrected to cAMP/10(6) cells. Sigmoid Emax and Emax models were fit to the cAMP response, isoproterenol concentration data by nonlinear regression analysis. Propranolol caused a nonsignificant increase in EC50 (median 3.2-fold) in blacks and a significant increase in EC50 (median 13.4-fold) in whites. The median calculated Ki values for propranolol were 9.2 nM in blacks and 1.2 nM in whites and median receptor occupancies at propranolol 15 nM were 64.3% in blacks and 92.5% in whites. A median propranolol concentration of 114 nM would have been needed in the black subjects to achieve a 92.5% receptor occupancy. These data suggest that the affinity of the beta-receptor for propranolol was greater in whites than blacks, thus equal propranolol concentrations resulted in greater beta-blockade in whites. This study suggested that for blacks and whites to achieve similar levels of beta-blockade, blacks needed a 7-fold higher concentration of propranolol. It is concluded racial differences in beta 2-receptor affinity for propranolol may help explain the documented racial differences in response.
Johnson
J A
JA
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis 38163.
D000328:Adult; D044383:Black People; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D012016:Reference Values; D012044:Regression Analysis; D044465:White People
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol