Role of different subtypes of adrenoceptors in pressor responses to catecholamines released from sympathetic nerve endings.
The role of alpha 1- and alpha 2-adrenoceptors in the vascular effects of catecholamines, either released locally from sympathetic nerve endings (e.g., in vascular smooth muscle) or derived from the adrenal medulla or administered intravenously, was studied using selective antagonists of these adrenoceptors. The ganglionic stimulant dimethylphenyl-piperazinium-iodide (DMPP) exerted dual actions on blood pressure: a rapid and short-term pressor reaction (phase I) resulting from catecholamine release elicited by ganglion stimulation, followed by a more sustained blood pressure elevation (phase II) resulting from the circulating catecholamines released from the adrenal medulla. The selective alpha 2-adrenoceptor, but a not subtype selective, antagonist 7,8-(methylenedioxi)-14-alpha-alloberbane HCl (CH-38083) (50-100 micrograms/kg, IV) significantly (p < 0.05) inhibited the pressor effects of epinephrine and norepinephrine given intravenously and phase II of the DMPP-induced pressor reaction. Idazoxan exerted similar effects, but at higher doses (400-600 micrograms/kg, IV). WB-4101 (50-100 micrograms/kg, IV) and BRL-44408 (2-3 mg/kg, IV), two selective alpha 2A-adrenoceptor antagonists, had the same activity as CH-38083, except did not inhibit the pressor effect of intravenously administered norepinephrine. The alpha 2B-adrenoceptor selective antagonist, ARC-239 (150 micrograms/kg, IV) did not influence phase II of DMPP-induced pressor reaction. Prazosin (200 micrograms/kg, IV), an antagonist of alpha 1 and alpha 2B-adrenoceptors, reduced blood pressure, the pressor response to intravenously administered epinephrine, and phase I of the DMPP-induced pressor effect. In addition, it completely inhibited the pressor responses to DMPP remaining after administration of CH-38083. These results suggest that the postsynaptically located alpha 1- and alpha 2(A and B)-adrenoceptors are involved in pressor response to norepinephrine and epinephrine, and are sensitive and accessible to catecholamines released locally from the axon terminals, and from the circulation to a different extent. These results may have great therapeutical importance in hypertension, for which the involvement of both a high level of circulating and locally released catecholamines may be indicative of the usefullness of a combination (alpha 1- and alpha 2-adrenoceptors- and Ca-channel-blocking agents) therapy.
Dóda
M
M
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D002415:Cats; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D005731:Ganglionic Stimulants; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D001599:Berberine; C048886:7,8-(methylenedioxy)-14-hydroxyberbane; D004246:Dimethylphenylpiperazinium Iodide; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D009638:Norepinephrine; D011224:Prazosin; C072125:BRL 44408