α-adrenergic blocking properties of quinine HCl

In the anesthetized dog, quinine HCl (50 mg/kg, i.v.) infused over a 20 min period produced a 22% maximum decrease in diastolic blood pressure, a 53% increase in pulse pressure and a 52% increase in myocardial contractile force. The initial positive inotropic response was maximal in the first 5-15 min of the quinine infusion and decreased to near control levels 40 min following the quinine infusion. Quinine caused a marked reduction in the noradrenaline (NA) pressor response, blockade of the adrenaline (A) pressor response, partial blunting of the angiotensin II (AII) pressor effect but no change in the depressor effect of isoprenaline (I). The positive inotropic effects of CaCl₂ were reduced and the duration of contractile action to both I and CaCl₂ was significantly prolonged by quinine. In isolated rabbit thoracic aortic strips, quinine produced a parallel, dose-related shift of the concentration-response curve for NA to the right but did not affect the maximum responses. A pA₂ of 4.91 was estimated by the method of Schild. The determined line had a slope of -0.84 which is similar to a theoretical slope of -1.0 and indicates a direct relationship between the number of receptors occupied and the contractile response. The responses to AII and histamine (H) were not altered by quinine. These results suggest that quinine HCl produces α-adrenergic blockade; additionally, quinine modifies catecholamine- and calcium-induced myocardial contractile force responses.