Pre- and postganglionic stimulation-induced noradrenaline overflow is markedly facilitated by a prejunctional beta 2-adrenoceptor-mediated control mechanism in the pithed rat.
The aim of the study was to further explore the prejunctional beta-adrenoceptor-mediated control mechanism of noradrenaline release from sympathetic nerves in response to preganglionic nerve stimulation (PNS) and local nerve stimulation of the portal vein, respectively, in the pithed rat. Baseline values as well as the increments of mean arterial blood pressure (delta-BP), heart rate (delta-HR) and plasma noradrenaline levels (delta-NA) in response to four PNS episodes (0.8 Hz, 3 ms, 75 V for 45 s at 20 min intervals), respectively, were evaluated. Fenoterol administration (0.25 mg/kg, i.v.) reduced significantly the basal blood pressure but did not alter delta-BP in response to PNS. Basal heart rate markedly increased after fenoterol without any further change in heart rate induced by PNS. The beta 1-selective antagonist CGP 20712A attenuated delta-BP in response to PNS and prevented the fenoterol-induced increase in basal heart rate. The beta 2-selective antagonist ICI 118,551 per se did not change the blood pressure and heart rate values, but antagonized the fenoterol-induced decrease in basal blood pressure. Fenoterol enhanced plasma delta-NA in response to PNS by 105% in comparison to the corresponding control value. This effect of fenoterol could be blocked by pretreatment with ICI 118,551 but not with CGP 20712A (a selective beta 1-adrenoceptor antagonist) which per se did not significantly change plasma delta-NA. Repeated local stimulation of the portal vein (S1-S3, 2 Hz, 3 ms, 10 mA, for 120 s at 30 min intervals) increased portal plasma noradrenaline without changing mean blood pressure and heart rate in pithed rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicinal Chemistry and Molecular Pharmacology, University of Groningen, The Netherlands.
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State / Q000503:physiopathology; D005280:Fenoterol / Q000494:pharmacology; D005724:Ganglia / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011169:Portal Vein / Q000166:cytology / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D005280:Fenoterol; C026777:ICI 118551; C049763:CGP 20712A; D009638:Norepinephrine