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PubMedDate not supplied

Influence of Bay k 8644 on pressor effects of B-HT 920 and cirazoline in pithed cats.

We studied interactions between the putative calcium entry promotor Bay k 8644 and alpha 1-adrenoceptor-mediated increases in diastolic pressure elicited by cirazoline as well as alpha 2-adrenoceptor-mediated pressor responses induced by B-HT 920 in pithed cats. Bay k 8644 (0.01-1 mg/kg, i.a.) did not affect the log dose-pressor response curve of cirazoline, but slightly potentiated the increase in diastolic pressure elicited by B-HT 920. After attenuation of the B-HT 920-induced pressor effects by the calcium entry blocker nifedipine (0.1 mg/kg, i.a.), Bay k 8644 (0.1 mg/kg, i.a.) strongly enhanced the pressor response. The increase in diastolic pressure elicited by cirazoline was not affected by nifedipine (0.1 mg/kg, i.a.), and the addition of Bay k 8644 (0.1 mg/kg, i.a.) had no effect. We conclude that in contrast to the increase in diastolic pressure elicited by B-HT 920, calcium channels are not involved in the cirazoline-induced pressor responses in the pithed cat. The activation of the calcium channels by B-HT 920 is already so efficient that it cannot be further enhanced by Bay k 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMedDate not supplied

Calcium influx-dependent and -independent alpha 1-adrenoceptor-mediated processes of vasoconstriction in vivo do not operate via different alpha 1-adrenoceptor subtypes.

In pithed rats, the selective alpha 1-adrenoceptor agonists St 587 and cirazoline show preponderant calcium influx-dependent and -independent vasoconstriction, respectively. By using these agonists, selective (competitive) antagonists for either process of vasoconstriction were sought. For this purpose, antagonism was analyzed for eight structurally different antagonists (prazosin, BE 2254, AR-C239, R 28935, corynanthine, phentolamine, sulpiride, and chlorpromazine) opposing the pressor responses evoked by cirazoline and St 587. Where pA2 values (-log dose antagonist evoking a twofold shift for the agonist dose-response curve) could be calculated, no significantly different pA2 values against either agonist resulted. However, with respect to the slopes of the Schild plots, deviations from unity were found for prazosin, R 28935, AR-C239, sulpiride, and chlorpromazine, but not uniformly against both agonists. Following treatment with phenoxybenzamine (PB) (30 micrograms/kg) and nifedipine (1 mg/kg), which produced calcium influx-sensitive and -insensitive vasoconstriction to cirazoline, respectively, Schild plots were constructed for BE 2254, prazosin, and chlorpromazine. Using cirazoline as an agonist, unity slopes were now obtained for prazosin and chlorpromazine. The Schild plots of BE 2254 versus cirazoline after PB or nifedipine administration, however, exhibited a slope deviating from unity. For prazosin and chlorpromazine, identical pA2 values still resulted against both processes of vasoconstriction to cirazoline. The results are compatible with the view that alpha 1-adrenoceptors mediating calcium influx-dependent and -independent vasoconstriction in vivo are not distinctly different entities, but are separate recognition sites of the same receptor.

Adrenergic alpha-Antagonists↗