Role of tachykinins in enhancement of bradykinin-induced bronchoconstriction by captopril.
In anesthetized, mechanically ventilated guinea pigs, infusion of captopril (1 mg/kg/h), an angiotensin converting enzyme inhibitor, significantly enhanced bronchoconstriction induced by intravenous injection of bradykinin (BK; 0.1-30 nmol/kg). Pretreatment of guinea pigs with capsaicin (100 mu g/kg) slightly suppressed the bronchoconstriction by BK alone and almost all of the enhancement of BK-induced bronchoconstriction by captopril was suppressed. Intravenous injection of substance P (SP; 0.1-100 nmol/kg), neurokinin A (NKA; 0.1-30 nmol/kg) and neurokinin B (NKB; 0.1-30 nmol/kg) also induced dose-dependent bronchoconstriction but captopril treatment enhanced only the bronchoconstriction induced by SP. BK degradation in bronchoalveolar lavage fluid (BALF) in vitro was significantly suppressed by captopril (p < 0.05). Captopril infusion to guinea pigs significantly increased the levels of BK, SP, and NKA in BALF after BK injection (p < 0.05). FK224, an NK1 and NK2 receptor antagonist and SR 48968, an NK2 receptor antagonist, significantly suppressed the bronchoconstriction induced by BK alone (p < 0.01 and p < 0.05, respectively) as well as the enhancement by captopril (p < 0.01). It can be concluded that the enhancement of BK-induced bronchoconstriction by captopril was attributable to inhibition of the degradation of BK itself and thereby enhanced release of NKA and partly of SP from sensory nerves by BK.
Arakawa
M
M
Department of Anesthesiology, Kitasato University School of Medicine, Sagamihara, Japan.
Majima
M
M
Nagai
K
K
Goto
F
F
Katori
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D008297:Male; D015288:Neurokinin A / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D013373:Substance P / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001549:Benzamides; D010456:Peptides, Cyclic; D010880:Piperidines; C075570:FK 224; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; D002216:Captopril; D002211:Capsaicin; D001920:Bradykinin