Abstract
The locus of the negative chronotropic response to propranolol was studied in bilaterally vagotomized and respiration-controlled rats. Following results were obtained: 1) The heart rate reduction on intravenous (i. v.) injection of propranolol was most potent for L-, next for DL- and not significant for D-isomer; 2) The response to i. v. DL-propranolol was not affected by the medullospinal transection nor by pretreatment with hexamethonium bromide; 3) Intracisternal (i. C.) administration of DL-propranolol elicited a dose-relating decrease which was, however, not antagonized by i. C. addition of DL-isoproterenol which caused an increase only inconsistently and not related with dose of the preceding propranolol; and 4) I. C. DL-propranolol did not eliminate the positive chronotropic effect of i. v. injection of DL-isoproterenol. Results indicate a lack of significant central component in the β-adrenergic negative chronotropic response to i. v. applied propranolol, and suggest the heart rate decrease on the centrally administered propranolol arising in a mechanism other than its β-adrenergic blocking property.
