Differences between full and partial alpha-adrenoceptor agonists in eliciting phasic and tonic types of responses in the longitudinal smooth muscle of the rat portal vein.
The aim of the present investigation was to study, taking into account both quantitative and qualitative differences, the influence of full and partial alpha-adrenoceptor agonists on spontaneous myogenic activity in the rat portal vein. We found that the alpha-adrenoceptor agonists cirazoline, adrenaline, noradrenaline, phenylephrine, St 587, Sgd 101/75, B-HT 920 and UK-14,304 could increase the amplitude of the phasic myogenic contractions in the rat portal vein with apparent differences in EC50 and Emax values. In addition to an increase in phasic myogenic activity, the alpha-adrenoceptor agonists cirazoline, adrenaline, noradrenaline, and phenylephrine were also able (in higher concentrations) to increase the basal tone of the rat portal vein preparation, again with apparent differences in EC50 and Emax values. Changing the extracellular Ca2+ concentration from 0.9 mmol/l to 2.5 mmol/l had no influence on the phasic character and the concentration range in which St 587 and UK-14,304 increased spontaneous myogenic activity, although changes in amplitude and frequency of the spontaneous myogenic contractions were less pronounced at a higher extracellular Ca2+ concentration (2.5 mmol/l). By the use of Schild analysis with the competitive alpha-adrenoceptor antagonists prazosin (pA2 = 8.74) and 5-methyl-urapidil (pA2 = 8.37), it was established that the contractile responses to St 587 were mediated by the same alpha 1-adrenoceptor subtype as the phasic and tonic type of contraction elicited by phenylephrine as described in a previous study. The concentration-response curve of UK-14,304 was significantly shifted to the right by low concentrations of prazosin (3 nmol/l-30 nmol/l), indicating stimulation of alpha 1-adrenoceptors by UK-14,304 in the rat portal vein.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
H R
HR
Schwietert
D
D
Wilhelm
B
B
Wilffert
P A
PA
van Zwieten
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; C051731:chlorethylclonidine; D000068438:Brimonidine Tartrate; D003000:Clonidine; C014282:cirazoline; D002118:Calcium