Angiotensin II enhances responses to endothelin-1 in bovine bronchial smooth muscle.
Angiotensin II and endothelin-1 are putative mediators in asthma. In this study we have examined the effect of angiotensin II on endothelin-1-induced contractions in bovine bronchi and the receptor types involved in the response to these agonists. Angiotensin II alone is very low in potency, producing only small contractions. In the presence of angiotensin II 10(-7) or 3 x 10(-7) M, contractions evoked by endothelin-1 were markedly enhanced. The AII1-receptor antagonist, losartan, abolished this enhancement suggesting that angiotensin II exerts this effect via an AII1-receptor. The contraction evoked by endothelin-1 is mediated via an EtA-receptor subtype since the EtA-receptor antagonist FR139317 attenuated the response. This is offset by an inhibitory EtB-type receptor, resulting in a larger contraction when these receptors are desensitized. Indeed, the EtB-receptor agonist sarafotoxin S6c reversed methacholine-evoked tone in a concentration-dependent manner. In conclusion, angiotensin II potentiates contractions evoked by endothelin-1 in bovine bronchi. This may be a mechanism by which angiotensin II--which has little activity in bronchi--may evoke substantial changes in airway tone. Angiotensin II evokes this potentiation via AII1-receptors, whilst endothelin-1 evokes contraction via EtA-receptors, an action which is offset by an inhibitory effect of EtB-receptors.
Nally
J E
JE
Division of Neuroscience and Biomedical Systems, Glasgow University, UK.
Clayton
R A
RA
Wakelam
M J
MJ
Thomson
N C
NC
McGrath
J C
JC
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D002417:Cattle; D004357:Drug Synergism; D016232:Endothelins / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D019808:Losartan; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011945:Receptors, Angiotensin / Q000187:drug effects; D017466:Receptors, Endothelin / Q000819:agonists / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001381:Azepines; D001713:Biphenyl Compounds; D016232:Endothelins; D007093:Imidazoles; D007211:Indoles; D011945:Receptors, Angiotensin; D017466:Receptors, Endothelin; D013777:Tetrazoles; D000804:Angiotensin II; C079574:FR 139317; D019808:Losartan