Comparative antihypertensive effects and tissue distribution of beta adrenergic blocking drugs.
The precise mechanism of the antihypertensive action of beta adrenergic blocking drugs is not known. Both peripheral and central sites of action have been proposed. The comparative antihypertensive actions and tissue distribution of propranolol, pindolol and sotalol were investigated in both normotensive Sprague-Dawley and spontaneously hypertensive rats. From recordings of concurrent changes in blood pressure and heart rate it was observed that oral or subcutaneous administrations of both propranolol and pindolol, but not sotalol, consistently reduced blood pressure and heart rate. Tissue distribution of all three agents was determined after 14 days of treatment. Propranolol and a metabolite were concentrated in the hippocampus whereas pindolol was concentrated in the septum. Significant central concentrations of sotalol were not demonstrable. All three agents produced persistent peripheral beta adrenergic blockade. It is concluded that beta adrenergic blockade may not be the important mechanism of the antihypertensive action of beta adrenergic blocking drugs. A modification of central autonomic control mechanisms is proposed as a possible mechanism of action.
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007279:Injections, Subcutaneous; D008099:Liver / Q000032:analysis; D008168:Lung / Q000032:analysis; D008297:Male; D009206:Myocardium / Q000032:analysis; D010869:Pindolol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011433:Propranolol / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D013015:Sotalol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D000959:Antihypertensive Agents; D011433:Propranolol; D013015:Sotalol; D010869:Pindolol