Mechanism of acute vasodepressor responses elicited by tiprinast and disodium cromoglycate following intravenous injection in anesthetized dogs

Bolus intravenous injection of tiprinast at a 1 mg/kg but not a subsequent 3‐mg/kg dose produced a transient vasodepressor response and concurrent bradycardia in closed‐chest, anesthetized dogs. This pattern was analogous to that elicited by disodium cromoglycate (cromolyn) in another series of dogs. Prior exposure of dogs to a slow 15‐min infusion of either tiprinast or cromolyn (100)μg/kg/min for 15 min significantly attenuated the hypotensions and bradycardia produced by subsequent bolus injection of either agent. The infusions themselves failed to cause sustained, dose‐related decreases in either blood pressure or heart rate beyond those noted durning the first 3–5 min after initiation. Atropine (1 mg/kg, i.v.) pretreatment, bilateral vagotomy, or a combination of atropine and vagotomy each sifnificantly reduced these acute cardiovascular responses. It is concluded that tiprinast, like cromolyn, appears to elicit a cardiac reflec (Bezold‐Jarisch) in the anesthetized dog. The significance of this response, if any, in humans or in relation to the mechanism of antiallergic action(s) of these compounds is uncertain.