Effect of intracisternal application of 6-hydroxydopamine on the antihypertensive action of propranolol in the dog.
The antihypertensive effects of intravenous (i.v.) and intracisternal (i.cist.) dl-propranolol were studied in anesthetized hypertensive dogs pretreated with i.cist. administered 6-hydroxydopamine (6-OHDA, 600 micrograms/kg) one week previously. Acute neurogenic hypertension was elicited by sino-aortic denervation (deafferentation). In control (saline-pretreated) dogs, dl-propranolol given i.cist. (50 micrograms/kg) or i.v. (0.3 and 1 mg/kg) decreased both the rise in blood pressure and tachycardia induced by deafferentation. These hypotensive and negative chronotropic actions of i.v. (0.3 mg/kg) propranolol were suppressed by pretreatment with 6-OHDA. At a higher dose (1 mg/kg), i.v. propranolol always corrected hypertension and tachycardia in 6-OHDA-treated dogs as in control animals. After 6-OHDA, i.cist. propranolol (50 micrograms/kg) failed to decrease the rise in blood pressure in debuffered animals. Conversely, the bradycardia induced by i.cist. propranolol was more marked in 6-OHDA-treated dogs than in control animals. These results confirm that the antihypertensive action of propranolol can be partly explained by an action on the central nervous system. They support the hypothesis that the hypotension observed after intracisternal (and also after low does of i.v.) propranolol is dependent on the integrity of central catecholaminergic neurons. These studies suggest that the antihypertensive action of propranolol may be partly due to the blockade of central presynaptic beta-adrenoceptors.
D000344:Afferent Pathways / Q000601:surgery; D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects; D003714:Denervation; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006892:Hydroxydopamines / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D011433:Propranolol / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013997:Time Factors
D000959:Antihypertensive Agents; D002395:Catecholamines; D006892:Hydroxydopamines; D011943:Receptors, Adrenergic, beta; D011433:Propranolol