Rabbit aorta antagonist activities

A direct effect of AmB on cell function was suggested by in vitro experiments, which demonstrated a vasoconstrictor action of AmB in perfused afferent arterioles and isometrically contracting rings of rabbit aorta or renal artery, effects which were prevented in Ca -free medium and by Ca" " channel blockers or theophylline [103]. Thus, AmB-induced reductions in RBF or GFR are not secondary to activation of TGF, but due to its direct vasoconstrictor effect. A role for thromboxane A2 has also been suggested based upon partial inhibition of the AmB-induced vasoconstriction and reduction in GFR by pretreatment with ibuprofen or a thromboxane receptor antagonist [104]. 

Affinity of selected Oj-AR antagonists for the recombinant animal a,-AR subtypes (pKi= -log,, nM) and functional affinity for the Oj-ARs of vascular and lower urinary tract tissues (pKb= -logj Kb, nM, for inhibition of NA-induced contraction). R.A.= rat aorta RB.A.= rabbit aorta RB.U.= rabbit urethra H.P.=human prostate. The in vivo effects after i.v. administration in the dog model are also listed. Data represent the doses (pg/kg) active in inhibiting by 50% the urethral contractions induced by NA (UP), the doses active in lowering diastolic blood pressure (DBP) by 25%, and the ratio between them. The ratios between the in vitro potency (Kb) on rabbit aorta and urethra are also reported (1/2). 

Often the PGs formed in a perfused organ or tissue can be identified by directing the perfusate over a cascade of superfused assay tissues (6). The technique gains specificity by careful selection of the assay tissues and by addition of a mixture of antagonists (see 7) to other biologically active components (e.g. adrenaline, 5-HT, histamine). Indomethacin is also added to prevent intra-mural conversion to PGs by the assay tissues. For example, a combination of strips of bovine coronary artery (BCA), rabbit aorta (RbA), rabbit coeliac artery (RbCa), rat stomach (RS) and rat colon (RC) can be used to differentiate between most PGs and thromboxanes (see 2). 

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