Abstract-Experimentswere conducted on I I loosely restrained, conscious dogs which responded with vocalization in a dose-dependent manner to bradykinin (0.6-10 nmol) or acetylcholine (0.1-10 timol) injected into the femoral or the mesenteric artery through a chronically indwelling arterial catheter. Vocalization was taken as being to reflect the algogenic action of these substances. Administration of captopril (1 mg/kg, i.v.) potentiated the algogenic action of bradykinin but not that of acetylcholine injected into either artery. The magnitude of potentiation of the algogenic action was about 3-fold for bradykinin injected into the femoral artery and about 10-fold for that injected into the mesenteric artery. The potentiation can be interpreted in terms of inhibition of kininase 11 by captopril.The difference in potentiation by captopril of the algogenic action of bradykinin injected into the two arteries may reflect the difference in kininase 11 activity in the two arterial beds. Possible involvement of E-series prostaglandins in the potentiation was also discussed.D-3-mercapto-2-methylpropanoyl-L-proline (SQ 14,225 or captopril) is an orally active inhibitor of angiotensin I converting enzyme developed in the hope of its being useful in the diagnosis and treatment of patients with renin-dependent hypertension (1-3). SQ 14,225is capable of producing a sustained fall of blood pressure in renin-dependent models of hypertension (4, 5). Since angiotensin I converting enzyme also inactivates bradykinin as kininase 11 (6), SQ 14,225 augments the vasodepressor effect of intravenous bradykinin (1-3).This is true for the vasodilator effects of bradykinin or kallikrein injected intra-arterially (7).Thus, it can be anticipated that SQ 14,225 administered systemically would augment the algogenic effect of bradykinin. The present experiments were performed to elucidate this point. Since different mechanisms have been proposed to operate in the algogenic action of bradykinin in the hind limb (a somatic area) and in the gut (a visceral area) (8) experimentswere conducted in the two areas. Vocalization of conscious dogs to intra-arterial injection of algogenic substances is taken to reflect the algogenic action of these substances.
MATERIALS AND METHODSExperiments were performed on 11 mongrel dogs of either sex, weighing 6-8 kg.Polyvinyl tubing of about 0.6 mm in outer diameter was implanted in the femoral artery or in a branch of the ileal or jejunal (called simply mesenteric bellow) artery under pentobar bitone anaesthesia 4 or 5 days prior to the experiment. During the experiment the animals
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